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ARACOG: A Randomized Phase II Study of Androgen Receptor Directed Therapy on COGnitive Function in Patients Treated with Darolutamide or Enzalutamide (ARACOG)
To compare the effects of treatment with enzalutamide (ENZ) versus darolutamide (DARO) on the cognitive function of men with non-metastatic and metastatic castration-resistant prostate cancer (mCRPC) by comparing the change in the maximally changed cognitive domain from baseline in patients in each study arm by 24 weeks.
Stuart Bloom
Male
18 Years to old
Phase 2
STUDY00010912
STUDY00010912
Key inclusion criteria include:
Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
Progressive disease per PCWG3 criteria
Metastatic CRPC or non-metastatic CRPC (M0CRPC)
Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises at least 1 week apart, with the last PSA >2 ng/mL.
For mCRPC: metastatic disease documented by standard or novel imaging techniques OR for M0CPRC: no evidence of metastatic disease on standard imaging.
Surgically or medically castrated, with testosterone levels of <50 ng/dL. If the patient is medically castrated, continuous dosing with GnRHa must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study.
Eastern Cooperative Oncology Group (ECOG) performance status ≤2
Able to complete cognitive testing and patient reported outcome surveys in English.
Ability to swallow study tablets whole.
Able to provide informed consent.
Key exclusion criteria include:
Prior chemotherapy for treatment of CRPC. Patients who received chemotherapy for castrate-sensitive prostate cancer are still eligible provided chemotherapy was completed >6 months prior to study entry.
Use of investigational agents for the treatment of prostate cancer within 4 weeks of study entry.
Prior usage of ENZ or DARO.
Prior use of apalutamide
Prior use of investigational agents that act on the androgen axis.
Progression during treatment with abiraterone (PSA or radiographic progression). Must have < 12 weeks of abiraterone exposure prior to enrollment if given for treatment of CRPC. If used with radiation for high risk localized hormone sensitive disease, can enroll if no progression of disease during treatment with abiraterone (PSA or radiographic) and >6 months since last exposure to abiraterone.
Planned radiation treatment > 21 days during enrollment in the study.
Any active, or prior history of, brain metastasis that have not been treated and stabilized.
Active or history of seizures or seizure disorder.
Prior diagnosis of dementia or other neurologic impairment.
Use of chronic opiates (other than stable doses of opioids that in the view of the patient and investigator do not affect cognition).
Clinically significant history of falls or risk of falls at baseline (timed up-and-go (TUG) test time of >12 seconds).
Darolutamide, Enzalutamide, Darolutamide, Enzalutamide
Metastatic Prostate Cancer, Prostate Cancer Metastatic, Prostate Cancer, Castrate Resistant Prostate Cancer
Clinics and Surgery Center (CSC)
State Representation in Early Psychosis (STEP)
Our Center will focus on the unifying hypothesis that processes underlying state representation dysfunction are relevant to psychosis, providing a window into pathophysiologic heterogeneity and precision treatment. Our Center will study three species (nonhuman primates, mice, and humans) using eight methodologies (genetic manipulations, slice physiology, ensemble recordings, LFP, behavior, EEG, fMRI, cognitive training). We will use a central computational perspective to translate and integrate across species and methodologies: Changes in neural information processing that affect parameters underlying attractor dynamics and influence state representation processes. Such changes create observable effects in behavior and neurophysiology, which we will study through the lens of attractor network models to inform our understanding of pathophysiologic heterogeneity, clinical trajectories, and precision treatment.
Sophia Vinogradov
Male or Female
Not specified
N/A
STUDY00009964
STUDY00009964
Inclusion Criteria:
English proficiency, as determined by staff observation and participant self-report
Estimated IQ at or above 70, as estimated by the cognitive assessments
Additional Inclusion Criteria for Early Psychosis Participants:
Clinical diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, psychosis NOS, bipolar disorder with psychosis, or major depressive disorder with psychosis, with onset of psychotic symptoms within the previous 5 years
Achieved clinical stability, defined as outpatient status for at least one month prior to study participation plus clinically stable doses of psychiatry medications for at least one month prior to study participation
Exclusion Criteria:
Unable or unwilling to provide informed consent
The participant is unable to demonstrate adequate decisional capacity, in the judgment of the consenting study staff member, to make a choice about participating in the research study
Participant is pregnant
Participant is illiterate
Cannot pass the CMRR Subject Safety Screen due to MRI contraindications
Presence of a major neurological disorder
Previous clinically significant head injury or prolonged unconsciousness, as determined by the PI/Co-Is
Meets criteria for substance or alcohol dependence within 3 months of enrollment
The presence of any major medical condition that, in the opinion of the PI/Co-Is, would impede participation in the study or would put the participant at additional risk by participating
Additional Exclusion Criteria for Early Psychosis Participants:
Has participated in significant formal cognitive training programs, as determined by the PI/Co-Is
Meets criteria for clinical risk of suicidal behavior, as defined by:
Clinician judgement
A suicide attempt within 6 months of enrollment
Active suicidal ideation at screening or baseline, as indicated by the C-SSRS
Previous intent to act on suicidal ideation with a specific plan and/or preparatory acts within 6 months of enrollment, as indicated by the C-SSRS
Additional Exclusion Criteria for Control Participants:
Meets DSM-5 criteria for psychotic, bipolar, or autism spectrum disorder
Has a family history (1st degree relative) of psychotic, bipolar, or autism spectrum disorder Computerized Cognitive Training, Computerized Cognitive Training
Mental Health & Addiction
A PHASE 2, OPEN-LABEL, SINGLE-ARM, COHORT STUDY TO EVALUATE THE SAFETY, EFFICACY, AND PHARMACOKINETICS OF SPARSENTAN TREATMENT IN PEDIATRIC SUBJECTS WITH SELECTED PROTEINURIC GLOMERULAR DISEASES (EPPIK) (EPPIK)
Currently, there are no approved treatment options for pediatric subjects with proteinuric kidney conditions. The study will look at the safety, efficacy, and pharmacokinetic (PK) trial in children ≥1 to <18 years treated for up to 108 weeks with the drug sparsentan.
Michelle Rheault
Male or Female
up to 18 Years old
STUDY00013216
STUDY00013216
Inclusion Criteria:
• Child 1 to 18 years old
• Diagnosed by biopsy with specific types of glomerular disease & protein in the urine
• Blood pressure is within normal range for age
• Maintained on a stable dose of immunosuppressive medications
Exclusion Criteria:
• Weight less than 7.3 kg at screening.
• Disease due to to viral infections, drug toxicities, or cancer.
• Kidney function is below the minimum required
Sparsentan, Sparsentan, Sparsentan, Sparsentan
Rare Diseases, Children's Health, Kidney, Prostate & Urinary
Glomerulosclerosis, Immunoglobulin A Nephropathy, IgA Vasculitis, Alport Syndrome
A Phase II Multicenter, Randomized, Double-Blind, 12-Week Treatment, 3-Arm, Parallel-Group, Placebo-Controlled Study to Investigate the Efficacy, Safety and Tolerability of RO7017773 in Participants Aged 15 to 45 Years with Autism Spectrum Disorder (ASD)
Suma Jacob
All
15 Years to 45 Years old
Phase 2
STUDY00010423
STUDY00010423
Inclusion Criteria
Male and female participants with Autism Spectrum Disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
Wechsler Abbreviated Scale of Intelligence (WASI-II) >/= 50 at screening or within the last 12 months prior to screening
ASD or Autism diagnosis confirmed by Autism Diagnostic Observation Schedule (ADOS-2)
Body mass index within the range of 18.5 to 40 kg/m2
Female Participants: is eligible if she is not pregnant, not breastfeeding, and women of childbearing potential (WOCBP), who agree to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 28 days after the last dose of study drug
Language, hearing, and vision compatible with the study measurements as judged by the Investigator
Allowed existing treatment regimens should be stable for 8 weeks prior to screening. Investigator expects stability of these treatments and behavioral interventions for the duration of the study
In the Investigator's opinion, able to participate and deemed appropriate for participation in the study, capable of following the study SoA and able to comply with the study restrictions
In the Investigator's opinion, participation in the study or discontinuation of prohibited medication will not pose undue risks
Exclusion Criteria
Neurologic/Psychiatric Conditions:
Non-verbal individuals
Presence of chromosome 15q11.2 q13.1 duplication syndrome (Dup15q syndrome), known "syndromic" forms of ASD (confirmed per genetic results available at screening): fragile X syndrome, Prader Willi syndrome, Rett's syndrome, tuberous sclerosis, and Angelman syndrome, as well as genetic alterations strongly associated with ASD per genetic results available at screening affecting the following genes: CHD8, ANDP, SHANK3
Medical history of alcohol and/or substance abuse/dependence in the last 12 months or positive test for drugs of abuse at screening
Initiation of a major change in psychosocial intervention within 6 weeks prior to screening. Minor changes in ongoing treatment are not considered major changes
Clinically significant psychiatric and/or neurological disorder that may interfere with the safety or efficacy endpoints
Risk of suicidal behavior in the opinion of a certified clinician or as evidenced by a "yes" to questions 4 and/or 5 of Columbia-Suicide-Severity Rating Scale (C-SSRS) taken at screening and baseline with respect to the last 12 months, or any suicide attempt in the past 5 years
Unstable epilepsy/seizure disorder within the past 6 months or changes in anticonvulsive therapy within the last 6 months
Other Conditions:
Medical history of malignancy if not considered cured or if occurred within the last 3 years with the exception of fully excised non-melanoma skin cancers or in-situ carcinoma of the cervix that has been successfully treated
Concomitant disease, condition or treatment which would either interfere with the conduct of the study or pose an unacceptable risk to the participant in the opinion of the Investigator Prior/Concomitant Therapy
Use of prohibited medications or herbal remedies within 6 weeks or 5 half-lives (t1/2) prior to randomization
Prior/Concurrent Clinical Study Experience:
Donation or loss of blood over 500 mL in adults and 250 mL in adolescents within 3 months prior to randomization
Participation in an investigational drug study within 1 month or 5 times the t1/2 of the investigational molecule prior to randomization or participation in a study testing an investigational medical device within 1 month prior to randomization or if the device is still active Diagnostic Assessments
Confirmed clinically significant abnormality in hematological, chemistry or coagulation laboratory parameters
Positive test result at screening for hepatitis B surface antigen, hepatitis C virus (HCV, untreated), or human immunodeficiency virus (HIV)-1 and -2. HCV participants who have been successfully treated and who test negative for HCV RNA, may be considered eligible for entry into the study
Other Exculsions:
Uncorrected hypokalemia or hypomagnesaemia
Placebo, RO7017773, Placebo, RO7017773
Autism Spectrum Disorder (ASD)
A Phase 2, Randomized, Double-Blinded, Placebo-Controlled, Parallel-Group, Multicenter Trial to Evaluate the Safety and Tolerability, Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of 2 Dose Regimens of ARGX-117 in Adults With Multifocal Motor Neuropathy (ARDA)
This is a clinical trial to investigate the safety and tolerability, efficacy pharmacokinetics, pharmacodynamics, and immunogenicity of 2 dose regimens of ARGX-117 in adults with multifocal motor neuropathy (MMN). Two treatment cohorts of at least 24 participants each are planned for enrollment. This trial consists of a screening period, an IVIg dependency period (if applicable), an IVIg monitoring period, a double-blinded treatment period (DBTP), and a safety follow-up period.
Jeff Allen
All
18 Years to old
Phase II
STUDY00014092
STUDY00014092
Inclusion Criteria:
Capable of giving signed informed consent form (ICF)
Male/female at least 18 years of age at the time the informed consent form (ICF) is signed
Probable or definite MMN according to the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) (EFNS/PNS) 2010 guidelines at screening confirmed by the MMN Confirmation Committee (MCC)
Receiving a stable IVIg regimen before screening
IVIg treatment dependency confirmation by the MMN Confirmation Committee (MCC)
Immunization with the first meningococcal vaccine and pneumococcal vaccine, and the single Haemophilus influenza type B vaccine must be performed at least 14 days before IMP administration at V1 according to local country-specific immunization schedules. A documented history of vaccination against Neisseria meningitides, Haemophilus influenza type B, and streptococcus pneumonia will be permitted
Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Exclusion Criteria:
Any coexisting condition which may interfere with the outcome assessments
Clinical signs or symptoms suggestive for neuropathies other than MMN such as motor neuron disease or other inflammatory neuropathies
Severe psychiatric disorder, history of suicide attempt, or current suicidal ideation that in the opinion of the investigator could create undue risk to the participant or could affect adherence with the trial protocol.
Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection during the screening and/or IVIg monitoring period (IVMP).
Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of MMN or put the participant at undue risk (eg, SLE).
History of malignancy unless resolved by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of the IMP. Participants with the following carcinomas will be eligible:
Adequately treated basal cell or squamous cell skin cancer
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Incidental histological finding of prostate cancer
Clinical evidence of other significant serious diseases, have had a recent major surgery (including a splenectomy at any time), or who have any other condition in the opinion of the investigator, that could confound the results of the trial or put the participant at undue risk
Prior/concomitant therapy
Cyclophosphamide and/or rituximab and/or eculizumab and/or mycophenolate mofetil within 3 months prior to screening
Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP.
Positive serum test at screening for an active viral infection with any of the following conditions:
Hepatitis B virus (HBV) that is indicative of an acute or chronic infection
Hepatitis C virus (HCV) based on HCV antibody assay
HIV based on test results that are associated with an AIDS-defining condition
Current or history of (ie, within 12 months of screening) alcohol, drug, or medication abuse
Known hypersensitivity reaction to 1 of the components of the IMP or any of its excipients
Female participants with a positive serum or urine pregnancy test, lactating females, and those who intend to become pregnant during the trial or within 12 months after last dose of the IMP
ALT or AST ≥2 × upper limit of normal and total bilirubin ≥1.5 × upper limit of normal of the central laboratory reference range
An estimated glomerular filtration rate of ≤60 mL/min/1.73m2 ARGX-117, Placebo, ARGX-117, Placebo
Rare Diseases
Clinics and Surgery Center (CSC)
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Pitolisant on Excessive Daytime Sleepiness and Other Non-Muscular Symptoms in Patients with Myotonic Dystrophy Type 1, Followed by an Open-Label Extension
The study will be evaluating the safety and efficacy of Pitolisant drug in patients with Myotonic Dystrophy type I.
Peter Karachunski
All
18 Years to 65 Years old
Phase 2
STUDY00013984
STUDY00013984
Inclusion Criteria:
Is able to provide voluntary, written informed consent.
Has a diagnosis of DM1 confirmed by genetic testing (cytosine-thymine-guanine [CTG] repeat of ≥100) from the Screening Visit.
Male or female patients ages 18 to 65 years at the time of enrollment.
Has a Clinical Global Impression of Severity (CGI-S) assessment of moderate or severe for overall severity of EDS at Screening.
If on a wake-promoting treatment that could affect EDS (including stimulants, modafinil, and armodafinil):
Must be on a stable dose for at least 2 months prior to Screening and agree to continue the stable dose for the duration of the Double-Blind Treatment Phase of the study (dose adjustments will be permitted in the OLE Phase).
If not on a stable dose for 2 months prior to Screening, washout for 5 half-lives prior to randomization and agree to remain off these treatments for the duration of the Double-Blind Treatment Phase of the study.
Washout of cannabidiol and tetrahydrocannabinol for 28 days prior to randomization and agree to remain off for the duration of the Double-Blind Treatment Phase of the study.
Able to walk independently with or without an assistive device (e.g., cane, walker, orthoses allowed).
A patient who is a female of child-bearing potential (FCBP) must have a negative serum pregnancy test at the Screening Visit and negative urine pregnancy test at the Baseline Visit and agree to remain abstinent or use an effective method of non-hormonal contraception to prevent pregnancy for the duration of the study and for 21 days after final dose of study drug.
In the opinion of the Investigator, the patient is capable of understanding and complying with the protocol and administration of oral study drug.
Exclusion Criteria:
Has a diagnosis of another genetic or chromosomal disorder that is distinct from DM1 and that is not being managed adequately in the opinion of the Investigator.
Experiences <6 hours on average of sleep per night based on their sleep diary during Screening (patients need to record at least 7 of 10 consecutive nights including 2 nights that fall on a weekend in their sleep diary during Screening).
Consistently consumes >600 mg of caffeine per day and is unable/unwilling to reduce caffeine intake to <600 mg per day for the duration of the Double-Blind Treatment Phase of the study; caffeine intake should remain consistent during Screening and throughout the Double-Blind Treatment Phase of the study.
Does not agree to discontinue any prohibited medication or substances listed in the protocol.
Is currently breastfeeding or planning to breastfeed over the course of the study. Lactating women must agree not to breastfeed for the duration of the study (Double-Blind Treatment Phase and OLE Phase) and for 21 days after final dose of study drug.
Participation in an interventional research study involving another investigational medication or device in the 28 days prior to enrollment; patients who undergo a washout of an investigational medication of at least 5 half-lives can be enrolled in the Double-Blind Treatment Phase of the study. Patients considering participation in another interventional research study in the OLE Phase must consult with the Investigator who will consult with the Medical Monitor.
Has a primary diagnosis of severe psychiatric illness.
Patients taking antidepressants who have not been on a stable dose of their antidepressant for at least 12 weeks prior to Screening; for patients on a stable dose of their antidepressant for at least 12 weeks prior to Screening, must agree to continue their stable dose for the duration of the Double-Blind Treatment Phase of the study. Dose adjustments will be permitted in the OLE Phase. In the Double-Blind Treatment Phase of the study, antidepressants that are strong CYP2D6 inhibitors are exclusionary.
Has a history of sleep-disordered breathing or another underlying sleep disorder that in the opinion of the Investigator is a main contributory factor to the patient's EDS.
Has a diagnosis of end-stage renal disease (ESRD; estimated glomerular filtration rate [eGFR] of <15 mL/minute/1.73 m2) or severe hepatic impairment (Child-Pugh C).
Has a diagnosis of moderate or severe renal impairment (eGFR ≥15 to ≤59 mL/minute/1.73 m2) or moderate hepatic impairment (Child-Pugh B) at Screening or during the Double-Blind Treatment Phase.
Has a family history of sudden cardiac death, unexplained death, or death from a primary dysrhythmia potentially associated with QT prolongation in any family member (i.e., first degree relative such as parent, sibling, or offspring).
Has a history of unexplained syncope.
Has a history of long corrected QT interval (QTc) syndrome or corrected QT interval using Fridericia's formula (QTcF) >450 msec for males or >470 msec for females (QTcF = QT / 3√ RR) sustained atrial fibrillation (AF) or left ventricular ejection fraction <50%.
Has a history of documented symptomatic arrhythmias (e.g., ECG, Holter monitor).
Electrocardiogram abnormalities during a 10-second, 12-lead ECG at Screening of first degree atrioventricular block (AVB; PR interval >220 msec), QRS >120 msec, heart rate (HR) <50 beats per minute (bpm), marked T-wave abnormalities, more than single atrial premature complexes (APCs) or premature ventricular contractions (PVCs), left bundle branch block, or Brugada pattern type 1.
Note: Patients with 1st degree AVB with a PR interval >220 msec, who are treated prophylactically with an allowable implanted device are not excluded from the study.
Based on Holter monitor, any episode of 3rd degree AVB, any prolonged episode of second degree AVB (>2 episodes during waking hours, >6 episodes during sleep), any prolonged episode of 2nd degree AVB (>10 seconds), any asystole longer than 3.5 seconds, any run of ventricular tachycardia (VT) >6 beats, frequent runs of non-sustained VT (>5/24 hour), >400 PVCs/24 hours, AF or paroxysmal AF, or frequent or complex atrial arrhythmias.
Has history of New York Heart Association (NYHA) class III or class IV heart failure.
Has an implanted defibrillator or implanted biventricular pacemaker. Note: Patients with implanted univentricular pacemakers that are used prophylactically to prevent or treat bradycardia or heart block may be included.
Is receiving a medication known to prolong the QT interval.
Has a history of clinically significant hypokalemia or hypomagnesemia that cannot be adequately controlled by supplementation.
Has serum potassium or magnesium levels that are outside of the normal reference ranges and considered clinically significant at Screening. Patients with mild hyperkalemia that, in the opinion of the Investigator, does not pose an arrhythmia threat may be included.
Is receiving a concomitant medication that is known to be a strong cytochrome P450 (CYP) 2D6 inhibitor, a strong CYP3A4 inducer; or a centrally acting histamine 1 receptor (H1R) antagonist (sedating antihistamine).
Note: Patients who undergo a washout of these medications of at least 5 half-lives may be enrolled in the Double-Blind Treatment Phase of the study.
Note: Use of strong CYP2D6 inhibitors and strong CYP3A4 inducers is allowed during the OLE Phase; however, adjustment of pitolisant dose is required. Although not prohibited during the OLE Phase of the study, use of centrally acting or sedating H1R antagonists should be avoided.
Is a known CYP2D6 poor metabolizer (PM).
Regular use (more than twice per week) of any sleep-promoting treatments that could affect EDS and not willing to limit use to no more than twice per week during Screening and for the duration of the Double-Blind Treatment Phase of the study (use of sleep-promoting agents are not allowed within one day prior to study-related assessments).
Has abnormal laboratory values at Screening that are clinically significant as determined by the Investigator.
Has initiated any new or change in allied health therapies or interventions that can interfere with the study outcomes within 28 days prior to randomization and that are prohibited during the Double-Blind Treatment Phase of the study, based on the Investigator's judgment.
Has a current or recent (within 1 year) history of a substance use disorder or dependence disorder, including alcohol and caffeine use disorders as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V).
Has planned surgery during the Double-Blind Treatment Phase of the study; planned surgery is permitted during the OLE Phase.
Has a significant risk of committing suicide or suicidality based on history, routine psychiatric examination, Investigator's judgment, or who has an answer of "yes" on any question other than questions 1 to 3 on the Columbia-Suicide Severity Rating Scale.
Based on the judgment of the Investigator, is unsuitable for the study for any reason, including but not limited to an unstable or uncontrolled medical condition or one that might interfere with the conduct of the study, confound interpretation of study results, pose a health risk to the patient, or compromise the integrity of the study. Pitolisant Oral Tablet, Placebo oral tablet, Pitolisant Oral Tablet, Placebo oral tablet
Rare Diseases
Clinics and Surgery Center (CSC)
Efficacy and Mechanisms of Combined Aerobic Exercise and Cognitive Training in MCI (The ACT Trial)
This study will be a multi-site, single-blinded, randomized controlled trial (RCT) that will screen older adults with mild cognitive impairment (MCI) using 4 steps (over the phone, in-person interview including informed consent, medical verification, exercise stress test/magnetic resonance imaging [MRI]). We will enroll 128 participants (target 96 completers, assuming 25% attrition rate at 6 months). After baseline assessment, participants will be enrolled and randomized within age (65-74 years of age or ≥75 years of age) and study site (Minnesota or Rochester) strata centrally at the University of Minnesota (UMN) to one of four groups: ACT, cycling only, SOP only, or control with equal allocation and using a randomization scheme generated by our UMN biostatistician (CI: Vock). Group allocations will be concealed to all investigators and data collectors. The interventions will last for 6 months with 12-month follow-up. Outcomes include: 1) cognition: composite measures of executive function and episodic memory, 2) AD signature cortical thickness: composite using structural magnetic resonance imaging (MRI), 3) functional connectivity in DMN: resting-state using functional MRI (fMRI), 4) aerobic fitness, and 5) clinical and pathological AD conversion. Cognition and aerobic fitness will be assessed at baseline, 3, 6, 12, and 18 months; AD conversion at 6, 12, and 18 months; and AD signature cortical thickness and DMN at baseline, 6, 12, and 18 months. PIs Yu and Lin have developed and tested strategies in their preliminary studies to successfully ensure the protection of human participants.
Dereck Salisbury
Male or Female
18 Years and over
N/A
STUDY00001135
STUDY00001135
Inclusion Criteria:
-65 years and older ACT, Cycling Only, Cognitive Training Only, Stretching and Mental Stimulating Activities, ACT, Cycling Only, Cognitive Training Only, Stretching and Mental Stimulating Activities
Mild Cognitive Impairment
cognitive decline, memory complaint, mild cognitive impairment
A Phase IIa, Double-Blind, Randomized, Intracohort Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of EHP-101 in Patients with Diffuse Cutaneous Systemic Sclerosis
The primary objective of the study is to evaluate the safety and tolerability of selected doses of EHP-101 in patients with diffuse cutaneous systemic sclerosis (dcSSc) administered for up to 84 days (12 weeks).The secondary objectives of the study are to evaluate the:Treatment effect of selected doses of EHP-101 as measured by the Composite Response Index in dcSSc (CRISS) as well as all individual components of the CRISS following treatment of 84 days (12 weeks).
Jerry Molitor
All
18 Years and over
Phase 2
STUDY00010677
STUDY00010677
Inclusion Criteria:
Patients male and female ≥18 years and ≤74 years at the time of consent;
American College of Rheumatology/ European League Against Rheumatism 2013 Criteria for SSc; dcSSc (skin thickening on upper arms, upper legs, or trunk);
Documented SSc for up to 6 years from the first non-Raynaud's phenomenon with a total mRSS of ≥15;
No new or increased doses of immunosuppressants medications within 3 months prior to Screening;
Effective method of contraception for participants and their partners.
Exclusion Criteria:
Severe or unstable Systemic Sclerosis (SSc) or SSc with end-stage organ failure;
Patient with FVC <60%;
History of clinically significant medical condition or concurrent medical therapies that would exclude the patient, preclude participation in the clinical trial, influence response to study product, or interfere with study assessments;
History of gastrointestinal dysmotility requiring total parenteral nutrition or hospitalization within 6 months before Visit 1;
Any one of the following values for laboratory tests at screening:
Haemoglobin <9 g/dL;
Neutrophils <1.0 x 10^9/L;
Platelets <75 x 10^9/L;
Estimated creatinine clearance <50 mL/min according to the Cockcroft-Gault equation;
Serum transaminases >2.0 x upper normal limit;
Total bilirubin ≥1.5 x upper limit of normal. Patients will be randomized to receive EHP-101 or Placebo, Patients will be randomized to receive EHP-101 or Placebo, Patients will be randomized to receive EHP-101 or Placebo, Patients will be randomized to receive EHP-101 or Placebo
Arthritis & Rheumatic Diseases, Immune Diseases
Scleroderma, Systemic sclerosis, EHP-101 Oral Solution, dcSSc, diffuse, pathological processes, connective tissue disease, skin disease
Phase 1/2 Study to Evaluate Palbociclib (IBRANCE?) in Combination With Irinotecan and Temozolomide or in Combination with Topotecan and Cyclophosphamide in Pediatric Patients With Recurrent or Refractory Solid Tumors Protocol No.: ADVL1921/A5481092
This is a Phase 1/2 multicenter, open-label study to evaluate palbociclib in combination with either irinotecan (IRN) and temozolomide (TMZ) or topotecan (TOPO) and cyclophosphamide (CTX) chemotherapy in children, adolescents and young adults with recurrent or refractory solid tumors. The study consists of a non- randomized Phase 1 portion for recurrent or refractory solid tumors followed by potential non- randomized tumor specific cohort(s) and a randomized, Phase 2 portion for recurrent or refractory EWS.
Emily Greengard
All
2 Years to 20 Years old
Phase 2
STUDY00007068
STUDY00007068
Inclusion:
Histologically confirmed relapsed or refractory solid tumor as follows:
For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement. Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners is required OR availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or have refractory disease and at least evaluable disease in at least one site other than bone marrow that can be followed by imaging.
Age ≥2 and <21 years at the time of study entry.
Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
Adequate bone marrow function.
Absolute neutrophil count ≥1000/mm3;
Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
Hemoglobin ≥8.5 g/dL (transfusion allowed).
Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
Adequate liver function, including:
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.
Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit.
Exclusion:
Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 portion: prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ and did not progress while on these medications are eligible.
Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination.
Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
Prior irradiation to >50% of the bone marrow (see Appendix 9).
Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for >14 days.
Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
Hereditary bone marrow failure disorder.
QTc >470 msec.
History of clinically significant or uncontrolled cardiac disease, including:
History of or active congestive heart failure; if patient had congestive heart failure resolve and >1 year from resolution, patient will be considered eligible;
Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
Diagnosed or suspected congenital or acquired prolonged QT syndrome;
Need for medications known to prolong the QT interval;
Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
Left ventricular ejection fraction <50% or shortening fraction <28%.
Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
Severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
Palbociclib, Temozolomide, Irinotecan, Topotecan, Cyclophosphamide, Palbociclib, Temozolomide, Irinotecan, Topotecan, Cyclophosphamide
Ewing Sarcoma, Solid Tumors, Rhabdoid Tumor, Rhabdomyosarcoma, Neuroblastoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma
Ewing Sarcoma, EWS, Solid Tumor, Recurrent Solid Tumors, Refractory Solid Tumors, Bone Cancer, Bone Tumor, Bone Sarcoma, Soft Tissue Cancer, Soft Tissue Sarcoma, Recurrent Ewing Sarcoma, Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma, Pediatric Cancer, Childhood Cancer, Ewing Sarcoma Treatment, Palbociclib, CDK4/6 Inhibitor, Irinotecan, Temozolomide, Topotecan, Cyclophosphamide
MT2021-11: An Open-label, Single-arm, Multicohort, Phase 2 Study to Assess the Efficacy and Safety of Tabelecleucel in Subjects with Epstein-Barr Virus-associated Diseases
This study is intended to determine the clinical benefit of tabelecleucel (EBV-specific cytotoxic T-lymphocytes) in subjects with EBV-associated diseases.
Joseph Maakaron
All
Phase 2
STUDY00013494
STUDY00013494
Inclusion Criteria:
Diagnosis of EBV+ disorder
Eastern Cooperative Oncology Group performance status <= 3 for participants aged >= 16 years; Lansky score >= 20 for participants from 1 year to < 16 years
Adequate organ function test results, unless organ dysfunction is considered to be due to the underlying EBV-associated disease by the investigator
Cohort-specific Inclusion Criteria:
For participants with PID LPD:
Newly diagnosed or relapsed/refractory LPD confirmed by biopsy-proven EBV+ LPD or positive cerebrospinal fluid (CSF) cytology with or without radiographically measurable intracranial disease with EBV detected in CSF
Participant must have systemic measurable disease and/ or CNS measurable disease
Definitive therapy (eg, allogeneic HCT, gene therapy) for the underlying PID is planned
Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD, as determined by the investigator
For participants with AID LPD:
Newly diagnosed or relapsed/refractory LPD confirmed by biopsy-proven EBV+ LPD or positive CSF cytology, with or without radiographically measurable intracranial disease, with EBV detected in CSF
Participant must have systemic measurable disease and/ or CNS measurable disease
Participants who are human immunodeficiency virus positive (HIV+) must meet both of the following criteria: Have an HIV viral load assessed by reverse transcription-polymerase chain reaction (RT-PCR) below the lower limit of detection and CD4 >= 50 cells/μL within 6 months prior to the first dose of tabelecleucel
Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD, as determined by the investigator
For participants with CNS PTLD:
Newly diagnosed or relapsed/refractory EBV+ CNS PTLD histologically confirmed by biopsy-proven EBV+ CNS PTLD or positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF
Participant may have systemic and CNS disease or CNS disease only
Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ LPD, as determined by the investigator
For participants with EBV+ PTLD, where standard first line therapy (rituximab and/or chemotherapy) is not appropriate, including CD20-negative disease:
Newly diagnosed, biopsy-proven EBV+ PTLD
Ineligible for standard first-line therapy for EBV+ PTLD, as determined by the investigator
Participants must have systemic disease measurable per Lugano Classification criteria, except when contraindicated or mandated by local practice, then MRI may be used.
For participants with sarcoma, including LMS:
Newly diagnosed or failed systemic first-line therapy for EBV+ sarcoma. Participants with newly diagnosed disease should be ineligible for standard first-line therapy for EBV+ sarcoma, as determined by the investigator.
Biopsy-proven EBV+ sarcoma
Measurable disease using diagnostic PET/CT and/or MRI following RECIST 1.1 criteria
For participants with CAEBV:
Newly diagnosed or previously treated CAEBV
Detectable EBV viremia on at least 2 occasions at a minimum of 90 days apart
At least 3 active clinical findings (per Kimura H, et al. Front Immunol. 2017;8:1867) as: Fever >= 38.5°C; splenomegaly, lymphadenopathy, and/or hepatomegaly; cytopenia affecting at least 2 or 3 lineages in the peripheral blood (hemoglobin < 9 g/dL, platelets < 100 × 10^3/mL, neutrophils < 1 × 10^3/mL); hypogammaglobulinemia; hemophagocytosis; hepatitis; neuropathy; rash; and hydroa vacciniforme
For participants with EBV+ viremia with HLH:
Newly diagnosed or previously treated EBV+ viremia with HLH
A molecular diagnosis consistent with HLH-2004 trial (per Henter JI, et al. Pediatr Blood Cancer. 2007;48:124-31) OR 5 or more of the clinical symptoms (per Jordan MB, et al. Blood. 2011;118:4041-4052): Fever >= 38.5°C; splenomegaly; cytopenia affecting at least 2 or 3 lineages in the peripheral blood (hemoglobin < 9 g/dL, platelets < 100 × 10^3/mL, neutrophils < 1 × 10^3/mL); hypertriglyceridemia (fasting >= 265 mg/dL) and/or hypofibrinogenemia (<= 150 mg/dL); hemophagocytosis in bone marrow, spleen, lymph nodes, or liver; low or absent natural killer cell (NK-cell) activity; ferritin >= 500 ng/mL; and elevated soluble CD25
Exclusion Criteria:
Burkitt, T-cell (except in the setting of HLH), natural killer/T-cell lymphoma/LPD, Hodgkin, or transformed lymphoma
Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment
Suspected or confirmed Grade >= 2 acute graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system or extensive chronic GvHD per National Institutes of Health (NIH) consensus criteria at the time of the enrollment
Need for vasopressor or ventilatory support
Prior therapy (in order of increasing washout period) prior to enrollment as:
Within 4 weeks or 5 half-lives (whichever is shorter) for any investigational product and/ or any chemotherapy (systemic or intrathecal), targeted small molecule therapy, or antibody/biologic therapy. Note: prior anti-CD20 antibody use is permitted within the washout period if a subsequent disease response assessment indicates disease progression
Within <= 8 weeks for cellular therapies (EBV-CTLs, chimeric antigen receptor therapies directed at T cells or T-cell subsets, donor lymphocyte infusion, other CTLs); and/or therapies which could impact tabelecleucel function (anti-thymocyte globulin, alemtuzumab)
Unwilling to use protocol specified contraceptive methods
Women who are pregnant or breastfeeding
Ongoing need for daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis (protocol-specified dexamethasone is permitted and concludes by the time of enrollment)
For participants with PID LPD or AID LPD: history of prior allogeneic HCT or solid organ transplant Tabelecleucel, Tabelecleucel
Epstein-Barr Virus (EBV)-Associated Diseases, EBV+ Lymphoproliferative Disease With Primary Immunodeficiency (PID LPD), EBV+ Lymphoproliferative Disease With Acquired (Non-congenital) Immunodeficiency (AID LPD), EBV+ Posttransplant Lymphoproliferative Disease in Central Nervous System (CNS PTLD), EBV+ Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications, Lymphoproliferative Disorders, Allogeneic Hematopoietic Cell Transplant, Stem Cell Transplant Complications, EBV+ Sarcomas, Leiomyosarcoma, Chronic Active Epstein-Barr Virus (CAEBV), Chronic Active Epstein-Barr Virus With Hemophagocytic Lymphohistiocytosis (HLH), Lymphohistiocytosis, Hemophagocytic
Clinics and Surgery Center (CSC)
A Phase 2 Open-label, Dose Escalation Study of HST5040 in Subjects with Propionic or Methylmalonic Acidemia Followed by a 6-Month, Randomized, Double-blind, Placebo-controlled, 2-period Crossover and an Open-label, Long-term Extension (HERO)
Phase 2 Open-label, Dose Escalation Study Followed by a 6-Month, Randomized, Double-blind, Placebo-controlled, 2-period Crossover and an Open-label, Long-term Extension
Sue Berry
All
up to 18 Years old
Phase 2
STUDY00010175
STUDY00010175
Inclusion Criteria:
Confirmed diagnosis of symptomatic PA or MMA (Mutase)
Ages ≥ 2 years old.
History of Inadequate metabolic control while receiving standard of care (SoC).
Plasma MCA concentration > 3x upper limit of normal of the reference range at screening.
Stable supplementation dose of carnitine for at least 1 week prior to the entry in the study.
Exclusion Criteria:
Moderate-to-severely impaired cardiac function with LVEF < 45% by ECHO.
Clinically significant arrhythmia by Holter monitor.
QTcF > 450 msec
Moderate to severe chronic kidney disease with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2.
Exposure to any investigational therapy, apart for a COVID-19 vaccine, within the past 6 months prior to study entry.
Exposure to gene therapy for PA or MMA at any time prior to study entry.
History of organ transplantation (Part A and B only)
History of severe allergic or anaphylactic reactions to any of the components of HST5040. HST5040, Placebo, HST5040, Placebo
Children's Health, Rare Diseases
Clinics and Surgery Center (CSC)
A randomized phase II trial of adjuvant Pembrolizumab versus observation following curative resection for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153
The primary objective is to evaluate whether the addition of adjuvant Pembrolizumab following surgical resection improves disease free survival compared with observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size, regardless of PD-L1 TPS score.
Amit Kulkarni
All
18 Years to old
Phase 2
STUDY00010745
STUDY00010745
Inclusion Criteria:
The participant (or legally acceptable representative if applicable) must provide written informed consent for the study. The participant may also provide consent for future unspecified research samples. However, the participant may participate in the study without participating in the future unspecified research sample collection. NOTE: Initial informed consent will remain valid throughout the 12-week period between surgical resection and study registration unless, in the opinion of the treating investigator, the participant experiences a significant change in medical or mental status.
Males and females age ≥ 18 years at the time of consent.
ECOG Performance Status of 0-1 within 28 days prior to registration.
Patients must have undergone complete surgical resection of their stage I NSCLC between 4-12 weeks prior to registration and have negative surgical margins (R0).
NOTE: Both squamous and non-squamous histologies are allowed into the study. Cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus "non-squamous histology".
NOTE: Staging will be according to the AJCC 8th edition.
Pathological tumor size must be 1.0 - 4.0 cm in greatest dimension. NOTE: According to AJCC 8th edition, subjects with lepidic predominant adenocarcinoma should be staged based on their invasive tumor size and not their total tumor size (i.e., subjects with lepidic predominant tumors whose invasive tumor size is less than 1 cm are not eligible, even if their total tumor size is 1.0 cm or greater).
Surgery for this lung cancer must be completed at least 28 days prior to registration.
Must have either previous NGS and PD-L1 results available using the Dako 22C3 antibody or have archival tissue of surgical specimen from current diagnosis available to perform analyses. If prior PD-L1 results with Dako 22C3 antibody are not available from a CLIA-accredited laboratory, subjects must be able to provide 5 x 5µm unstained slides for prospective analysis to be used for stratification. If NGS results are not available, subjects must be able to provide at least 10 x 10µm unstained and 1 x 4µm H&E slides from current diagnosis for future NGS and/or other genetic analyses.
Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 28 days prior to registration.
Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. For subjects randomized to the pembrolizumab arm: If there is > 72 hours between the screening test and C1D1, another pregnancy test (urine or serum) must be performed and must be negative before the subject may start C1D1.
NOTE: Females are considered of childbearing potential unless: they are postmenopausal; are surgically sterile; or they have a congenital or acquired condition that prevents childbearing. See Section 5.1.4 for definitions.
NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) OR
A WOCBP who is using a highly effective contraceptive method (failure rate of <1% per year), or is abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) during the intervention period and for at least 120 days after the last dose of study drug. The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study drug. See contraceptive guidance in Section 5.1.4 of the protocol.
As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
Exclusion Criteria:
Current lung cancer is <1 cm or > 4 cm in size or is stage II, III, or IV.
Patients with tumors that are known to harbor actionable EGFR mutations.
Prior chemotherapy, radiation therapy, or immunotherapy for the treatment of this lung cancer.
Has a known active additional malignancy that is progressing or has required active treatment within the past 3 years. NOTE: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma in situ, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization.
Has had an allogenic tissue/solid organ transplant.
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has an active infection requiring systemic therapy.
Has a known history of Human Immunodeficiency Virus (HIV). Note: HIV testing is not required unless mandated by local health authority.
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: Hepatitis B and Hepatitis C testing is not required unless mandated by local health authority.
Has active TB (Bacillus Tuberculosis) infection.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Pembrolizumab, Pembrolizumab
NSCLC, Stage I
Clinics and Surgery Center (CSC)
A Phase 2, multicenter, open-label, non-randomized, proof-of-concept study evaluating the efficacy, safety, and tolerability of BIVV020 in adults with chronic inflammatory demyelinating polyneuropathy (CIDP)
The purpose of the study is to see if the drug (BIVV020) works to improve symptoms in three populations of adults who have chronic inflammatory demyelinating polyneuropathy (CIDP): • Participants currently on the standard of care (SOC) treatment. • Participants treated previously with the SOC but with no meaningful improvement. • Participants that have not been treated with the SOC. Additional purposes of the study are to find out how safe and tolerable the drug is.
Jeff Allen
Male or Female
18 Years and over
Phase II
STUDY00014727
STUDY00014727
Inclusion Criteria:
Adults ≥18 years of age at the time of signing the informed consent.
Documented definite or probable diagnosis of CIDP (typical CIDP, pure motor CIDP, or Lewis-Sumner Syndrome) according to the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) Task Force first revision.
Belonging to one of the following three groups: standard-of-care (SOC)-Treated, SOC-Refractory or SOC-Naive, as defined below.
SOC-Treated (all criteria a-c must be met): a) Documented evidence of objective response to SOC, with clinically meaningful improvement. Clinically meaningful improvement is defined as one of the following: ≥1-point decrease in adjusted INCAT score, ≥4 points increase in RODS total score, ≥3 points increase in MRC Sum score, ≥8 kilopascal improvement in mean grip strength (one hand), or an equivalent improvement based on information documented in medical records and per the PI's judgement. b) Must be on stable SOC therapy, defined as no change greater than 10% in frequency or dose of immunoglobulin therapy or corticosteroids within 8 weeks prior to screening, remaining at stable SOC therapy until the time of first SAR445088 dosing. c) Evidence of clinically meaningful deterioration on interruption or dose reduction of SOC therapy within 24 months prior to screening, determined by clinical examination or medical records. Clinically meaningful deterioration is defined as one of the following: ≥1-point increase in adjusted INCAT score, decrease in RODS total score ≥4 points, decrease in MRC Sum score ≥3, mean grip strength worsening of ≥8 kilopascals (one hand), or an equivalent deterioration based on information from medical records and at the PI's judgement.
SOC-Refractory (all criteria a-d must be met): a) Evidence of failure or inadequate response to SOC defined as no clinically meaningful improvement and persistent INCAT score ≥2 after treatment for a minimum of 12 weeks on SOC prior to screening. A clinically meaningful improvement is defined as one of the following: ≥1-point decrease in adjusted INCAT score, increase in RODS total score ≥4 points, increase in MRC Sum score ≥3, mean grip strength improvement of ≥8 kilopascals (one hand), or equivalent improvement based on information from medical records and at the PI's judgement.
Or
Unable to receive or continue treatment with immunoglobulins or corticosteroids due to side effects.
b) Patient has not received immunoglobulins (IVIg or SCIg) within 12 weeks prior to screening. c) Certain immunosuppressant drugs are allowed in this group if taken for ≥6 months and at a stable dose for ≥3 months prior to screening: azathioprine, methotrexate, mycophenolate mofetil and cyclosporine. Oral corticosteroids are allowed if on a stable dose of <20 mg/day of prednisone (or equivalent dose for other oral corticosteroids) for ≥3 months prior to screening. d) INCAT score: 2-9 (a score of 2 should be exclusively from leg disability component of INCAT).
SOC-Naive (all criteria a-c must be met): a) Participants without previous treatment for CIDP or participants who received immunoglobulins (IVIg or SCIg) or corticosteroids but were stopped for reasons other than lack of response or side effects. b) Not treated with immunoglobulins (IVIg or SCIg) or corticosteroids for at least 6 months prior to screening. c) INCAT score: 2-9 (a score of 2 should be exclusively from leg disability component of INCAT.
Documented vaccinations against encapsulated bacterial pathogens given within 5 years of enrollment or initiated a minimum of 14 days prior to first dose
A female participant must use a double contraception method including a highly effective method of birth control from inclusion and up to 52 weeks plus 30 days after the last study dose and agree not to donate eggs, ova or oocytes during this period.
A female participant must have a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours before the first dose of study intervention.
Male participants, whose partners are of childbearing potential must accept to use, during sexual intercourse, a double contraceptive method according to the following: condom plus an additional highly effective contraception
Male participants must have agreed not to donate sperm during the intervention and up to 52 weeks after the last dose.
Capable of giving signed informed consent
Exclusion Criteria:
Polyneuropathy of other causes, including but not limited to hereditary demyelinating neuropathies, neuropathies secondary to infection or systemic disease, diabetic neuropathy, drug- or toxin-induced neuropathies, multifocal motor neuropathy, polyneuropathy related to IgM monoclonal gammopathy, POEMS syndrome, lumbosacral radiculoplexus neuropathy, pure sensory CIDP and acquired demyelinating symmetric (DADS) neuropathy (also known as distal CIDP).
Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments.
Poorly controlled diabetes (HbA1c >7%).
Serious infections requiring hospitalization within 30 days prior to screening and any active infection requiring treatment during screening.
Clinical diagnosis of SLE.
Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. Specifically, history of any hypersensitivity reaction to SAR445088 or its components or of a severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibody.
Participants with a history of suicidality in the six months prior to screening or currently at risk of committing suicide.
Presence of conditions (medical history or laboratory assessments) that may predispose the participant to excessive bleeding or increased risk of infection.
Evidence of CIDP relapse within 6 weeks after receiving a vaccination.
Recent or planned major surgery that could confound the results of the trial or put the participant at undue risk.
Treatment with plasma exchange within 12 weeks prior to screening.
Prior treatment with rituximab or ocrelizumab in the 6 months prior to SAR445088 dosing or until return of B-cell counts to normal levels, whichever is longer.
Immunosuppressive/chemotherapeutic medications such as azathioprine, methotrexate, cyclophosphamide, cyclosporine, mycophenolate mofetil, tacrolimus, interferon, TNF-alpha inhibitor: within 6 months prior to dosing (except for some cases as indicated in the SOC-Refractory group).
Treatment (any time) with highly immunosuppressive/chemotherapeutic medications with sustained effects, eg, mitoxantrone, alemtuzumab, cladribine.
Treatment (any time) with total lymphoid irradiation or bone marrow transplantation.
Use of any specific complement system inhibitor (eg, eculizumab) within 12 weeks or 5 times the half-life of the product, whichever is longer, prior to screening.
Pregnant (defined as positive β-HCG blood test) or lactating females.
Positive result on any of the following tests: hepatitis B surface (HBsAg) antigen, anti-hepatitis B core antibodies (anti-HBc Ab)-unless anti-hepatitis B surface antibodies (anti-HBs Ab) are also positive , indicating natural immunity-, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2 antibodies).
Evidence of IgG4 autoantibodies against paranodal proteins (NF155 and CNTN1).
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. SAR445088 (IV), SAR445088 (SC), SAR445088 (IV), SAR445088 (SC)
Rare Diseases
CIDP, Clinics and Surgery Center (CSC)
Fecal Microbiota Transplant for Postoperative Crohn's Disease
People with Crohn's disease often need surgery. The gut bacteria of people with Crohn's is associated with Crohn's disease coming back after surgery. Fecal microbiota transplant (FMT) after surgery might be a way to prevent Crohn's disease from coming back after surgery. This study aims to determine if fecal microbiota transplant (FMT) taken by capsules results in the same amount of good bacteria in the guts as FMT by colonoscopy in people with Crohn's disease who have had surgery. Participants will be randomized to get FMT by capsules or colonoscopy. Colonoscopy with biopsies 8-weeks after the FMT will be used to assess the good bacteria in the gut.
Byron Vaughn
All
18 Years to old
Phase 1
STUDY00014833
STUDY00014833
Inclusion Criteria:
Able and willing to sign informed consent form
Age 18 or older
English speaking
Established CD for at least 6-months based on typical clinical, endoscopic, and histopathic evidence.
Prior ileocecal resection for CD
Stable medications for 30 days
Women of reproductive age: Agree to remain abstinent or use effective birth control
Able and willing to comply with all study procedures
Exclusion Criteria:
Antibiotic therapy within 15 days
Probiotic therapy within 15 days
Adenomatous polyps that have not been removed
Anticipated antibiotic use over the study period
Subtotal or total colectomy
Current ostomy (ileostomy or colonoscopy)
Anticipated surgical procedure over study period
Pregnancy
Severe food allergy
Diagnosis of end stage liver disease or cirrhosis
Absolute neutrophil count < 500 cell / uL
Life expectancy < 6 months Capsule fecal microbiota material (cap-FMT), Colonoscopic fecal microbiota material (colo-FMT), Capsule fecal microbiota material (cap-FMT), Colonoscopic fecal microbiota material (colo-FMT)
Crohn Disease
Clinics and Surgery Center (CSC)
A Phase II, Multi-center, Open-Label Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of R3R01 in Alport Syndrome Patients with Uncontrolled Proteinuria on ACE/ARB Inhibition and in Patients with Primary Steroid-Resistant Focal Segmental Glomerulosclerosis
The main purpose of this study is to check how safe the study drug is and how well your body handles taking it. The study will also check: • if the study drug works to improve your kidney function • whether the study drug has an impact on your daily life • the amount of the study drug in your blood over a period of time (called pharmacokinetics)
Michelle Rheault
All
12 Years to old
Phase II
STUDY00015869
STUDY00015869
Inclusion Criteria:
All Patients:
Patient is able to communicate well with the investigator, understands and is willing to comply with all requirements of the study, and understands and signs the written informed consent form (ICF).
For children to be eligible, one or both parents must sign a parental permission form which provides information contained in the ICF. Children capable of assent must express their willingness to participate by signing an assent form.
Blood pressure in the normotensive or hypertensive range. Patients who are on stable ACEi/ARB doses with systolic blood pressure (SBP) SBP > 90 mmHg and diastolic blood pressure (DBP) > 60 mmHg
If patient has received a COVID vaccination, the baseline visit must occur at least one week or more after the second/booster vaccination.
Patients who have had active symptoms of COVID within 3 months prior to screening and are now asymptomatic for the last 2 weeks but have tested COVID PCR positive. If a patient is asymptomatic at screening but is COVID positive, then rescreening can occur after a minimum of two weeks.
Both female patients, as well as, female partners of male patients who are of child-bearing potential must be willing to not become pregnant for the complete duration of the study (>180 days) (90 days after the last dose of study medication).
Males (including sterilized subjects) whose female partners have child-bearing potential, must agree to use male contraception (condoms) during the period from the time of signing the informed consent form (ICF) through 90 days after the last dose of study drug. They must agree to immediately inform the investigator if their partner becomes pregnant during the study.
Alport Syndrome Patients Inclusion Criteria (in addition):
Males and females with X-Linked AS and males and females with autosomal inherited AS.
For countries that are enrolling pediatric patients: patients from age 12 years and older.
For countries that are not enrolling pediatric patients: patients from age 18 years and older.
Confirmed diagnosis of AS by genetic testing and /or kidney biopsy.
UPCR ≥1.0 g/g.
eGFR ≥ 45 mL/min/1.73m2 (using MDRD equation for adults and Bedside Schwartz equation for children).
ACEi/ARB therapy at maximum tolerated dose stable for at least 4 weeks prior to screening. ACEi/ARB dose should remain stable over the course of the study.
Focal Segmental Glomerulosclerosis Patients Inclusion Criteria (in addition):
Male or female patients,
For countries that are enrolling pediatric patients: patients from age 12 years and older.
For countries that are not enrolling pediatric patients: patients from age 18 years and older.
Primary FSGS, (without any identifiable cause, and where the FSGS is confirmed by renal biopsy) or FSGS where there is documentation of a genetic mutation in a podocyte protein associated with FSGS.
Steroid-resistance defined as failure to achieve partial or complete remission, or experienced adverse events without acceptable clinical benefit after at least 8 weeks of adequate corticosteroid therapy for children and 12 weeks for adults.
UPCR between 3.5g/g and 12.0g/g.
eGFR > 45 mL/min/1.73m2 (using MDRD equation for adults and Bedside Schwartz equation for children).
If taking concomitant ACEi and/or ARB treatment, it should remain at a stable dose for a minimum of 28 days prior to enrollment and during the course of the study.
Exclusion Criteria:
All Patients:
Uncontrolled diabetes mellitus as evidenced by an HbA1c ≥ 11%.
Uncontrolled hypertension
Adults: (SBP ≥ 180mmHg and/or DBP ≥ 100mmHg).
Children: ≥ 95th percentile or ≥ 130/80 mm Hg, whichever is lower
Moderate or severe hepatic impairment (Child-Pugh B or C), except if (a) decreased serum albumin is directly related to the renal disease (resulting in a Child Pugh score of 7), and (b) no other Child-Pugh Score parameters are increased and (c) patient has no liver pathology in medical history.
Presence of any active (i.e., with symptoms) and/or uncontrolled infection (including COVID).
Human immunodeficiency virus (HIV).
BMI > 40.
History of malignancy other than treated basal cell or squamous cell skin cancer within the past 5 years.
History of alcohol abuse in the last 5 years or currently drinks in excess of 21 and 14 units per week for males and females, respectively.
Received an investigational agent within 30 days or 5 half-lives prior to screening (whichever is longer).
History of non-compliance such that patient is unlikely to be compliant with study visits, procedures or drug administration.
Patient has had an organ transplant, is currently on an organ transplant waiting list or there is a reasonable possibility that the patient will have an organ transplant in the 6 months after screening.
Participation in an interventional trial within the previous 3 months prior to screening or concurrent participation in a research trial.
Patient is not suitable to participate in the study for any reason (including, but not limited to co-morbidities, history of non-compliance with study visits, procedures, or drug administration) in the opinion of the investigator.
Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) are excluded from participation in the study unless they agree to use highly effective contraception.
Females that are lactating.
History of hypersensitivity to study drug and/or any of its excipients.
Patients with hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
Required concomitant use of bardoxolone, rituximab, cyclo-phosphamide, abatacept, SGLT2 inhibitors, or sparsentan
Alport Syndrome Patients Exclusion Criteria (in addition):
Kidney disease apart from AS, e.g. diabetic nephropathy or lupus nephritis.
Use of Bardoxolone, SGLT2 inhibitors or sparsentan treatment in the 30 days prior to screening.
Focal Segmental Glomerulosclerosis Patients Exclusion Criteria (in addition):
Patient has collapsing variant of FSGS on renal biopsy.
Patient has FSGS secondary to another condition (e.g. obesity, cardiovascular, infectious, or autoimmune disorder).
Use of Rituximab, cyclophosphamide or abatacept treatment in the 120 days prior to screening. If taking other chronic immuno-modulatory medications that are small molecules, the dosage must be stable for 4 weeks prior to screening.
If previous Rituximab treatment is greater than 120 days from screening, CD20 cell count should be within normal limits.
If previous other antibody treatment on a stable dose is greater than 120 days from screening, the investigator must deem administration of study drug to be safe.
Use of SGLT2 inhibitors or sparsentan treatment in the 30 days prior to screening. R3R01, R3R01
Alport Syndrome, Focal Segmental Glomerulosclerosis
Clinics and Surgery Center (CSC)
KIN-1902-2001: A Randomized, Double-blind, Placebo-controlled Phase 2 Study with Open-label Extension to Assess the Efficacy and Safety of Namilumab in Subjects with Chronic Pulmonary Sarcoidosis (RESOLVE-Lung)
Primary Objective: The primary objective of this study is: • To evaluate the efficacy of namilumab in subjects with chronic pulmonary sarcoidosis (CPS). Key Secondary Objective: • To evaluate the effect of namilumab on proportion of subjects on OCS taper without rescue. Other Secondary Objectives: The other secondary objectives of this study are: • To assess the safety and tolerability of namilumab; • To assess the effect of namilumab on measures of pulmonary function; • To assess the effect of namilumab on Patient Reported Outcomes (PROs): o St. George’s Respiratory Questionnaire (SGRQ); o Modified King’s Sarcoidosis Questionnaire (mKSQ); o Fatigue Assessment Scale (FAS); o Subject Global Assessment (SGA); o Leicester Cough Questionnaire (LCQ); o Pain Visual Analog Scale (VAS); o General Sleep Disturbance Scale (GSDS); o Bothersomeness and Subject Global Impression of Change (BSGIC). • To assess the effect of namilumab on dyspnea; • To assess the effect of namilumab on cumulative OCS use and toxicity; • To assess the effect of namilumab on the rate of clinical benefit; • To evaluate the effect of namilumab on clinical worsening. • To assess the effect of namilumab on sarcoid associated skin lesions (when present); • To assess the effect of namilumab on the severity of extrapulmonary organ involvement; • To assess the effect of namilumab on use of rescue therapy; • To assess the population pharmacokinetics (PPK) and exposure-response (E-R) relationships for efficacy and safety of namilumab; • To assess the effect of namilumab on laboratory parameters; • To assess the efficacy of namilumab on the radiologic features of CPS; • To assess the effect of namilumab on 6-Minute Walking Distance (6MWD).
Maneesh Bhargava
All
18 Years to old
Phase II
STUDY00014721
STUDY00014721
Inclusion Criteria :
Male or female age ≥18 years
Able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form
Greater than or equal to 6-month history of documented sarcoidosis including histological confirmation in the subject's medical records
Evidence of sarcoidosis as indicated by: a) HRCT consistent with Pulmonary Sarcoidosis AND; b) Medical Research Council Dyspnea scale >1 (i.e., Grade 2 or more) AND; c) One or more of the following is present: i) Screening FDG-PET consistent with pulmonary sarcoidosis AND SUVmax ≥ 3; ii) Recent history of worsening sarcoidosis; iii) Recent history that tapering OCS and/or ISTs resulted in an increase of pulmonary disease
Body Mass Index (BMI) ≤ 40 kg/m2 at Screening
Vaccinations for COVID-19 with completion of the primary series at least 2 weeks prior to randomization
Exclusion Criteria
Hospitalized for any respiratory illness ≤ 30 days prior to or during Screening
Greater than or equal to 20% fibrosis as indicated on HRCT-scan assessed by central read prior to randomization
Hemoglobin ≤ 9.5 g/dL
Participation in another interventional clinical trial (IP/Device) within 6 months prior to Screening, during screening and throughout the duration of the study
ECG abnormalities that warrant further clinical investigation or management at Screening
Systolic blood pressure (SBP) <90 or >180mm Hg; Diastolic blood pressure (DBP) <60 or >110 mm Hg at Screening
Has documented laboratory-confirmed SARS-CoV-2 infection with pulmonary involvement or signs/symptoms of long COVID as determined by approved testing ≤ 6 months prior to randomization
Other significant pulmonary disease or conditions that prevent subject from performing acceptable spirometry
Females who are pregnant or breastfeeding or intend to be during the course of the study
Any other acute or chronic medical condition, psychiatric condition, or laboratory abnormality, that in the judgment of the Investigator or Sponsor, may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results, and would make the participant inappropriate for entry into this study
Subjects who are treatment naive
Other protocol-defined inclusion/exclusion criteria apply.
Namilumab, Placebo, Namilumab, Placebo
Sarcoidosis, Pulmonary
Clinics and Surgery Center (CSC)
Remote State Representation in Early Psychosis (Rem-STEP) (Rem-STEP)
The purpose of the current study is to test the effects of two forms of cognitive training: visual perception training or visual cognitive control training in individuals with early psychosis.
Melissa Fisher
Male or Female
18 Years and over
Phase II
STUDY00015419
STUDY00015419
Inclusion Criteria:
Diagnosis of one of the following conditions: Schizophrenia; Schizoaffective disorder; Schizophreniform disorder; Psychosis NOS; Major depressive disorder with psychotic features; or Bipolar disorder with psychotic features (confirmed with MINI 7.0 diagnostic interview)
Between the ages of 18-45 at the time of screening
Willing to share contact information for a clinical provider
Fluent in spoken and written English, in that the participant learned to speak English before the age of 12 or is able to demonstrate fluency in conversation with study staff
Has an outpatient status and no hospitalization for psychiatric reasons for at least 1 month prior to participant
Has access to a computer with internet connection
Has a United States address as permanent residence
Exclusion Criteria:
History of severe substance use in the past 3 months (determined by the MINI 7.0 diagnostic criteria)
Unable to demonstrate adequate decisional capacity, in the judgment of the consenting study staff member, to make a choice about participating in the research study
Significant cognitive training experience within the last 6 months, as determined by the PI
Diagnosed with a neurological disorder (Autism spectrum disorder is allowed) BrainHQ Computerized Cognitive Training - Visual Perception Training Paradigm, BrainHQ Computerized Cognitive Training - Visual Cognitive Control Training Paradigm, BrainHQ Computerized Cognitive Training - Visual Perception Training Paradigm, BrainHQ Computerized Cognitive Training - Visual Cognitive Control Training Paradigm
Mental Health & Addiction
Cognitive Training, Remote, Online, Clinical Trial
Mechanisms of a Dynamic Stability Approach
If you have been referred to occupational therapy for thumb carpometacarpal osteoarthritis and you are 18 years or older, you are eligible for this study. Arthritis is the leading cause of disability in the United States, with an estimated 25.6 million Americans affected by osteoarthritis (OA) of the hand. Thumb carpometacarpal osteoarthritis (thumb carpometacarpal (CMC) joint osteoarthritis) is the most common and limiting form of hand osteoarthritis, causing chronic pain, weakness, reduced joint movement, and difficulty carrying out common daily tasks. The purpose of this research study is to find out if an 8-week dynamic stability program can help people with a range of CMC OA severity and symptoms. Dynamic stability (DS) is a new occupational therapy program that uses a series of exercises to strengthen specific muscles around the thumb CMC joint. By strengthening these muscles, the DS approach aims to reduce joint pain, delay further damage, and improve function and participation in daily activities. If you enroll, we expect that you will be in this research study for 9 weeks, for a total of about 15 hours of participation. During the study, you will participate in: 4 occupational therapy (OT) study visits (about 60 minutes each), a home exercise program (15-20 minutes/day) for 8 weeks and, 2 assessment visits (Baseline, and week 9) where we will using Computerized Tomography, a type of X-ray, and ultrasound to take measures of your affected joint and have you complete questionnaires related to pain and disability.
Corey McGee, PhD, MS, OTR/L, CHT
Male or Female
18 Years and over
Phase 2
STUDY00015249
STUDY00015249
Inclusion Criteria:
• Thumb Carpometacarpal (CMC) Osteoarthritis confirmed by xray
• Referred to occupational therapy for treatment of thumb CMC osteoarthritis
Exclusion Criteria:
• Cortisone treatments to the affected thumb within the prior three months
• Hand rehabilitation within the past six months
• thumb CMC joint replacement
• Diagnosis of inflammatory arthritis
Dynamic Stability Exercise Program, Dynamic Stability Exercise Program
Arthritis & Rheumatic Diseases, Bone, Joint & Muscle
Clinics and Surgery Center (CSC), Arthritis, Hand Arthritis, Occupational Therapy, Carpometacarpal, Osteoarthritis, Thumb joint
ROWAN: An Open-Label, Prospective, Multi-Center, Randomized Clinical Trial To Evaluate The Efficacy and Safety Of TheraSphereTM followed by Durvalumab (Imfinzi?) With Tremelimumab, Versus TheraSphereTM Alone For Hepatocellular Carcinoma (HCC). (ROWAN)
We are studying a new treatment for people who have a liver tumor that will be treated with TheraSphere™, a device that delivers radiation directly to the tumor. The study will determine if adding immunotherapy medications after TheraSphere™ treatment is safe and can improve results in comparison with participants that receive only TheraSphere™.
Siobhan Flanagan
All
18 Years to old
Phase 2
STUDY00016193
STUDY00016193
Inclusion Criteria:
Participants must be aged ≥18 years at the time of screening.
Written informed consent and any locally required authorization (e.g., Health Insurance Portability and accountability Act in the US, European Union (EU) data privacy regulations in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
Life expectancy ≥6 months.
HCC, diagnosed by radiographic imaging or histology.
Patient not a candidate for liver resection, thermal ablation, or transplantation at the time of study entry.
Treatment naïve.
Measurable disease by mRECIST criteria (e.g. ≥10mm of enhancement).
Tumor volume ≤25% of whole liver volume (determined by imaging).
Unilobar tumor
Future liver remnant volume (FLRV) ≥30% of whole liver volume. FRLV is the volume of liver not planned to be treated with TheraSphere and free of HCC.
Patients with HBV or HCV infection are to have documented virology status of hepatitis as confirmed by HBV and HCV serology test:
Patients with HBV infection: HBV DNA load should be ≤2000 IU/mL obtained within 28 days prior to initiation of study treatment, and Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study
Patients with chronic HCV infection are allowed in the study: for untreated patients, AST/ALT should be ≤3xULN and for treated patients, antiviral treatment (per local standard of care) should be stopped for a minimum of 14 days prior to study entry and AST/ALT should be ≤3xULN
Patient with Human Immunodeficiency Virus (HIV) infection is eligible with well controlled HIV infection, no current or previous AIDS-related complications and CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
Negative serum pregnancy test in females of child-bearing potential; patients who are breast-feeding cannot participate in this trial.
Adequate contraception for the patient and his/her sexual partner.
Adequate renal and marrow function as defined below:
Hemoglobin ≥9.0 g/dL
Absolute neutrophil count ≥1.5 x 109/L
Platelet count ≥75 x 109/L
Measured or calculated creatinine clearance ≥45 mL/min as determined by Cockcroft-Gault (using actual body weight)
Absolute lymphocyte count ≥1.0 X 109/L
Adequate liver function, as defined by
Child-Pugh A
Serum albumin ≥30 g/L
Serum bilirubin <1.1 x the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be permitted to enroll in the study in consultation with their physician.
AST and ALT <3 x ULN.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 at randomization.
Body weight >30 kg and BMI ≥18 kg/m2.
Exclusion Criteria:
Any contraindication to angiography or selective visceral catheterization.
Cone Beam CT (CBCT) or Technetium-99m macroaggregated Albumin (99mTc-MAA) hepatic arterial perfusion scintigraphy shows any deposition to the gastrointestinal tract that may not be corrected by angiographic techniques.
CBCT or 99mTc-MAA hepatic arterial perfusion scintigraphy shows poor tumor targeting that would lead to a dose that does not meet the protocol specified liver dosing criteria, if lobar administration with multi-compartment dosimetry is planned.
Shunting of blood to the lungs that could result in delivery of >30 Gy to the lungs in a single treatment or >50 Gy cumulative dose to the lungs in case of multiple TheraSphere treatments, as seen on 99mTc-MAA hepatic arterial perfusion scintigraphy.
Extrahepatic metastases, including patients with hilar /mesenteric /celiac lymph nodes >1.5 cm in shorter axis, or with lung nodules (single lesion, > 1 cm, or multiple smaller lesions with a total diameter >2 cm)
Brain metastases, leptomeningeal carcinomatosis or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry.
Evidence of any tumor vascular invasion.
Any prior treatment for HCC including surgery, TACE/TAE, ablation, systemic, and/or radiation treatment (including radiation treatment to the liver for any diagnosis).
Prior exposure to any immune mediated therapy, including but not limited to other anti PD-1, anti-PDL-1, anti-PDL2, anti-CTLA-4, antibodies, IFN.
Concurrent treatment for HCC or treatment in the last 4 weeks in another clinical study, unless it is an observational study (non-interventional) or during a non-interventional follow-up stage of an interventional study, or prior randomization to this study
Hepatic encephalopathy present at study entry and/or episodes of encephalopathy (≥Grade 2) within 6 months prior to randomization.
Presence of ascites, clinical or radiological, "trace" of ascites is acceptable.
HCC with infiltrative disease presentation that is not possible to evaluate by mRECIST.
History of active primary/acquired immunodeficiency.
Evidence of pulmonary insufficiency (defined by an arterial oxygen pressure (Pa,O2) of <60 mmHg, or oxygen saturation (Sa,O2) of <90% (Roussos & Koutsoukou, 2003) or clinically evident chronic obstructive pulmonary disease (COPD).
Medical history of radiation pneumonitis or recent pneumonitis, regardless of causality
History of any organ allograft, including bone marrow allo and autograft.
Active or prior documented autoimmune or inflammatory disorders (including but not limited to, inflammatory bowel disease [e.g. ulcerative colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
Patients with vitiligo or alopecia
Patients with hypothyroidism (e.g. following Hashimoto's syndrome) stable on hormone replacement therapy
Any chronic skin condition that does not require systemic therapy.
Patients without active disease in the last 5 years may be included but only after consultation with the Sponsor Study physician.
Patients with celiac disease controlled by diet alone.
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra-articular injection)
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication).
History of gastrointestinal bleeding within 28 days prior to randomization, active GI bleeding and any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device). Patients with known varices that have not bled can enter the study. No endoscopic exploration is required before randomization.
Presence of biliary stent at any time or sphincterotomy within one year prior to randomization.
History of malignancy, other than HCC, within three years, with the exception if adequately treated carcinoma in situ of the cervix, early squamous cell carcinoma or basal cell carcinoma of the skin, localized prostate cancer, ductal carcinoma in situ, or low grade endometrial carcinoma with no myometrial invasion (negligible risk of metastases or death 5-year OS rate >90%).
Major surgical procedure (as defined by the Investigator) within 28 days prior to randomization.
A history of severe allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically.
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), HBV and HVC co-infection, HBV and Hep D co-infection, or human immunodeficiency virus (HIV 1/2 antibodies) plus HCV or HBV co-infection.
Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab and/or tremelimumab. Note: patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and/or tremelimumab and up to 30 days after the last dose of durvalumab and/or tremelimumab.
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab and tremelimumab monotherapy.
Unstable chronic disease or evidence of any disease or condition that would place the patient at undue risk and preclude safe use of TheraSphere, durvalumab and tremelimumab treatment, including but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
Patient not able to follow the TheraSphere, durvalumab or tremelimumab treatment requirements. TheraSphere Y-90 glass microsphere therapy, Durvalumab (Imfinzi) immunotherapy, Tremelimumab immunotherapy, TheraSphere Y-90 glass microsphere therapy, Durvalumab (Imfinzi) immunotherapy, Tremelimumab immunotherapy
Hepatocellular Carcinoma
Carcinoma, Carcinoma, Hepatocellular, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Adenocarcinoma, Liver Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Digestive System Diseases, Liver Diseases
COG AHEP1531 - Pediatric Hepatic Malignancy International Therapeutic Trial (PHITT)
This partially randomized phase II/III trial studies how well cisplatin and combination chemotherapy works in treating children and young adults (≤ 30 years of age) with hepatoblastoma or liver cancer after surgery. Drugs used in chemotherapy, such as cisplatin, doxorubicin, fluorouracil, vincristine sulfate, carboplatin, etoposide, irinotecan, sorafenib, gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving combination chemotherapy after surgery may kill more tumor cells.
Emily Greengard
All
to 30 Years old
Phase 2/Phase 3
STUDY00003718
STUDY00003718
Inclusion Criteria:
Patients in Group F must have a body surface area (BSA) >= 0.6 m^2
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Patients must be newly diagnosed with histologically-proven primary pediatric hepatic malignancies including hepatoblastoma or hepatocellular carcinoma, except as noted below; patients with a diagnosis of hepatocellular neoplasm, not otherwise specified, should be classified and treated per hepatoblastoma treatment arms; note that rapid central pathology review is required in some cases; please note: all patients with histology as assessed by the institutional pathologist consistent with pure small cell undifferentiated (SCU) HB will be required to have testing for INI1/SMARCB1 by immunohistochemistry (IHC) according to the practices at the institution
Patients with histology consistent with pure SCU must have positive INI1/SMARCB1 staining
For all Group A patients, WDF status as determined by rapid review will be used to further stratify patients to Group A1 or A2
For Groups B, C and D, rapid review is required if patients are either >= 8 years of age or have an alphafetoprotein (AFP) =< 100 at diagnosis
For all Groups E and F patients, rapid central pathology review is required
In emergency situations when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy
Clinical situations in which emergent treatment may be indicated include, but are not limited to, the following circumstances:
Anatomic or mechanical compromise of critical organ function by tumor (e.g., respiratory distress/failure, abdominal compartment syndrome, urinary obstruction, etc.)
Uncorrectable coagulopathy
For a patient to maintain eligibility for AHEP1531 when emergent treatment is given, the following must occur:
The patient must have a clinical diagnosis of hepatoblastoma, including an elevated alphafetoprotein (AFP), and must meet all AHEP1531 eligibility criteria at the time of emergent treatment
Patient must be enrolled on AHEP1531 prior to initiating protocol therapy; a patient will be ineligible if any chemotherapy is administered prior to AHEP1531 enrollment
Note: If the patient receives AHEP1531 chemotherapy emergently PRIOR to undergoing a diagnostic biopsy, pathologic review of material obtained in the future during either biopsy or surgical resection must either confirm the diagnosis of hepatoblastoma or not reveal another pathological diagnosis to be included in the analysis of the study aims
Patients may have had surgical resection of the hepatic malignancy prior to enrollment; all other anti-cancer therapy for the current liver lesion is prohibited
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 or
A serum creatinine based on age/gender as follows:
Age: maximum serum creatinine (mg/dL)
1 month to < 6 months: 0.4 (male and female)
6 months to < 1 year: 0.5 (male and female)
1 to < 2 years: 06 (male and female)
2 to < 6 years: 0.8 (male and female)
6 to < 10 years: 1 (male and female)
10 to < 13 years: 1.2 (male and female)
13 to < 16 years: 1.5 (male), 1.4 (female)
>= 16 years: 1.7 (male), 1.4 (female)
Total bilirubin =< 5 x upper limit of normal (ULN) for age
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 10 x upper limit of normal (ULN) for age
Shortening fraction of >= 28% by echocardiogram (for patients on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior to study enrollment) or
Ejection fraction of >= 47% by echocardiogram or radionuclide angiogram (for patients on doxorubicin-containing regimens [Groups C, D, E2, and F] assessed within 8 weeks prior to study enrollment)
Group F patients only: QT/corrected QT (QTc) interval =< 450 milliseconds for males and =< 470 milliseconds for females (assessed within 8 weeks prior to study enrollment)
Normal pulmonary function tests (including diffusion capacity of the lung for carbon monoxide [DLCO]) if there is clinical indication for determination (e.g. dyspnea at rest, known requirement for supplemental oxygen) (for patients receiving chemotherapy [Groups A, B, C, D, E2, F]); for patients who do not have respiratory symptoms or requirement for supplemental oxygen, pulmonary function tests (PFTs) are NOT required
All patients and/or their parents or legal guardians must sign a written informed consent
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
Prior chemotherapy or tumor directed therapy (i.e. radiation therapy, biologic agents, local therapy (embolization, radiofrequency ablation, and laser); therefore, patients with a pre-disposition syndrome who have a prior malignancy are not eligible
Patients who are currently receiving another investigational drug
Patients who are currently receiving other anticancer agents
Patients with uncontrolled infection
Patients who previously received a solid organ transplant, other than those who previously received an orthotopic liver transplantation (OLT) as primary treatment of their hepatocellular carcinoma
Patients with hypersensitivity to any drugs on their expected treatment arm
Group C: Patients who have known deficiency of dihydropyrimidine dehydrogenase (DPD)
Group D:
Patients with chronic inflammatory bowel disease and/or bowel obstruction
Patients with concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment
Group F:
Patients with peripheral sensitive neuropathy with functional impairment
Patients with a personal or family history of congenital long QT syndrome
These criteria apply ONLY to patients who may receive chemotherapy (all groups other than Group E1):
Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
Lactating females who plan to breastfeed their infants
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
Note for Group F: patients of childbearing potential should use effective birth control during treatment with sorafenib and for at least 2 weeks after stopping treatment Carboplatin, Cisplatin, Doxorubicin, Etoposide, Fluorouracil, Gemcitabine, Irinotecan, Laboratory Biomarker Analysis, Oxaliplatin, Patient Observation, Resection, Sorafenib, Vincristine Sulfate, Carboplatin, Cisplatin, Doxorubicin, Etoposide, Fluorouracil, Gemcitabine, Irinotecan, Laboratory Biomarker Analysis, Oxaliplatin, Patient Observation, Resection, Sorafenib, Vincristine Sulfate
Childhood Hepatocellular Carcinoma, Childhood Malignant Liver Neoplasm, Fibrolamellar Carcinoma, Hepatoblastoma, Hepatocellular Malignant Neoplasm, Not Otherwise Specified
Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP)
A multicenter, randomized, adaptive allocation clinical trial to determine if increasing durations of induced hypothermia are associated with an increasing rate of good neurological outcomes and to identify the optimal duration of induced hypothermia for neuroprotection in comatose survivors of cardiac arrest.
Benjamin Miller
All
18 Years to old
Phase II/III
STUDY00011864
STUDY00011864
Inclusion Criteria:
Coma after resuscitation from out of hospital cardiac arrest
Cooled to <34 deg C with 240 minutes of cardiac arrest
Definitive temperature control applied
Age ≥ 18 years
Informed consent from legal authorized representative (LAR) including intent to maintain life support for 96 hours
Enrollment within 6 hours of initiation of cooling
Exclusion Criteria:
Hemodynamic instability
Pre-existing neurological disability or condition that confounds outcome determination
Pre-existing terminal illness, unlikely to survive to outcome determination
Planned early withdrawal of life support
Presumed sepsis as etiology of arrest
Prisoner Therapeutic Hypothermia, Therapeutic Hypothermia
Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced, Hypoxia-Ischemia, Brain
Bayesian Adaptive Clinical Trial, Coma, Hypothermia, therapeutic
A Phase 2/3, Two-Part, Open-Label, Dose Escalation, Age De-escalation and Randomized, Observer-Blind, Placebo-Controlled Expansion Study to Evaluate the Safety, Tolerability, Reactogenicity, and Effectiveness of mRNA-1273 SARS-CoV-2 Vaccine in Healthy Children 6 months to < 12 Years of Age (mRNA-1273-P204) - COVID-19
The Sponsor of this study, ModernaTX, is studying the mRNA-1273 vaccine for the prevention of COVID-19 in children. This study is being conducted to learn about the safety, any side effects, and how your child’s body responds to the study vaccine (the “immune response”).
Shane McAllister
All
6 Months to 11 Years old
Phase 2/Phase 3
STUDY00012613
STUDY00012613
Key
Inclusion Criteria:
For participants with chronic diseases (such as, asthma, diabetes mellitus, cystic fibrosis, human immunodeficiency virus [HIV] infection), the disease should be stable, per investigator assessment.
Investigator assessment that the parent(s)/legally acceptable representatives understand and are willing and physically able to comply with protocol mandated follow-up, including all procedures, written informed consent is provided, and participants provide assent.
For children 2 years of age or older has a body mass index at or above the third percentile according to World Health Organization (WHO) Child Growth Standards at the Screening Visit.
For children 6 months to <12 months of age: born at full-term with a minimum birth weight of 2.5 kilograms (kg).
For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection, agreement to continue adequate contraception or abstinence through 3 months following the second injection (Day 29) and the third dose in Part 3 (Day 149/booster dose Day 1), and not currently breastfeeding.
Key Exclusion Criteria:
Known history of SARS-CoV-2 infection within 2 weeks prior to administration of vaccine or known close contact with anyone with laboratory-confirmed SARS-CoV-2 infection or COVID-19 within 2 weeks prior to administration of vaccine.
Prior administration of an investigational or approved CoV (such as, SARS-CoV-2, SARS CoV, Middle East Respiratory Syndrome CoV) vaccine.
Treatment with investigational or approved agents for prophylaxis against COVID 19 (such as, receipt of SARS-CoV-2 monoclonal antibodies) within 6 months prior to enrollment.
Known hypersensitivity to a component of the vaccine or its excipients.
A medical or psychiatric condition that, according to the investigator's judgment, may pose additional risk as a result of participation, interfere with safety assessments, or interfere with interpretation of results.
History of a diagnosis or condition that, in the judgment of the investigator, may affect study endpoint assessment or compromise participant safety.
Received any non-study vaccine within 14 days before or after any dose of vaccine (except for seasonal influenza vaccine, which is not permitted within 14 days before or after any dose of vaccine)
Received intravenous or subcutaneous blood products (red blood cells, platelets, immunoglobulins) within 3 months prior to Day 1
Participated in an interventional clinical study within 28 days prior to Day 0 or plans to donate blood products while participating in this study. mRNA-1273, Placebo, mRNA-1273.214, mRNA-1273, Placebo, mRNA-1273.214
SARS-CoV-2
mRNA-1273, mRNA-1273 vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, COVID-19, COVID-19 Vaccine, Moderna
HEALEY ALS Platform Trial
The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. The trial is designed as a perpetual platform trial. This means that there is a single Master Protocol dictating the conduct of the trial. The Master Protocol describes the overall framework of the platform trial, including the target population, inclusion and exclusion criteria, randomization scheme, study endpoints, schedule of assessments, trial design, the mechanism for adding and removing interventions, and the statistical methodology and recommended statistical methods for evaluating interventions. Interventions (i.e., investigational products) are tested in trial regimens. Each trial regimen is described in its own Regimen-Specific Appendix (RSA) to the Master Protocol. The RSA will describe the nature of the intervention and its mechanism of action (MoA) including the mode and frequency of administration, dosage, the specific target population (to be selected within the pre-defined subsets of the Master Protocol), additional enrollment criteria (if any), sample size, and other specific intervention-related information and assessments (safety or other assessments that may be in addition to those outlined in the Master Protocol).
David Walk
All
18 Years to old
Phase 2/Phase 3
STUDY00010021
STUDY00010021
Inclusion Criteria:
Sporadic or familial ALS diagnosed as clinically possible, probable, lab-supported probable, or definite ALS defined by revised El Escorial criteria.
Age 18 years or older.
Capable of providing informed consent and complying with study procedures, in the SI's opinion.
Time since onset of weakness due to ALS ≤ 36 months at the time of the Master Protocol Screening Visit.
Vital Capacity ≥ 50% of predicted capacity for age, height, and sex at the time of the Master Protocol Screening Visit measured by Slow Vital Capacity (SVC), or, if required due to pandemic-related restrictions, Forced Vital Capacity (FVC).
Participants must either not take riluzole or be on a stable dose of riluzole for ≥ 30 days prior to the Master Protocol Screening Visit. Riluzole-naïve participants are permitted in the study.
Participants must either not take edaravone or have completed at least one cycle of edaravone prior to the Master Protocol Screening Visit. Edaravone-naïve participants are permitted in the study.
Participants must have the ability to swallow pills and liquids at the time of the Master Protocol Screening Visit and, in the SI's opinion, have the ability to swallow for the duration of the study.
Geographically accessible to the site.
Exclusion Criteria:
Clinically significant unstable medical condition (other than ALS) that would pose a risk to the participant, according to SI's judgment (e.g., cardiovascular instability, systemic infection, untreated thyroid dysfunction, or clinically significant laboratory abnormality or EKG changes).
Lab abnormalities include, but are not limited to: Hemoglobin < 10 g/dL, White Blood Cells < 3.0 x 103/mm3, Neutrophils, Absolute ≤ 1000/mm3, Eosinophilia (absolute eosinophil count of ≥ 500 eosinophils per microliter), low platelet counts (< 150 x 109 per liter), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of normal (ULN), eGFR < 30 mL/min/1.73m2, thyroid-stimulating hormone (TSH) levels >10 mIU/L or <0.01 mIU/L.
Presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the participant to provide informed consent, in the SI's opinion.
Active cancer or history of cancer, except for the following: basal cell carcinoma or successfully treated squamous cell carcinoma of the skin, cervical carcinoma in situ, prostatic carcinoma in situ, or other malignancies curatively treated and with no evidence of disease recurrence for at least 3 years.
Use of investigational treatments for ALS (off-label use or active participation in a clinical trial) within 5 half-lives (if known) or 30 days (whichever is longer) prior to the Master Protocol Screening Visit.
Exposure at any time to any gene therapies under investigation for the treatment of ALS (off-label use or investigational).
If female, breastfeeding, known to be pregnant, planning to become pregnant during the study, or of child-bearing potential and unwilling to use effective contraception for the duration of the trial and for 3 months, or longer as specified in each RSA, after discontinuing study treatment.
If male of reproductive capacity, unwilling to use effective contraception for the duration of the trial and for 3 months, or longer as specified in each RSA, after discontinuing study treatment.
Anything that would place the participant at increased risk or preclude the participant's full compliance with or completion of the study, in the SI's opinion.
If a participant is being re-screened, the disqualifying condition has not been resolved, or the mandatory wash-out duration has not occurred.
For those participating in the optional CSF collection, contraindication to undergoing a lumbar puncture (LP) in the SI's opinion. Participants undergoing the LP must not be currently taking anticoagulation medications such as warfarin that would be a contraindication to LP; aspirin and non-steroidal anti-inflammatories are allowed. Zilucoplan, Verdiperstat, CNM-Au8, Pridopidine, SLS-005 Trehalose, Zilucoplan, Verdiperstat, CNM-Au8, Pridopidine, SLS-005 Trehalose
Rare Diseases
Clinics and Surgery Center (CSC)
A two-cohort, open-label, single arm, multicenter study to evaluate efficacy, safety and tolerability, pharmacokinetics and pharmacodynamics, of emapalumab in children and adults with macrophage activation syndrome (MAS) in Still s disease (including systemic juvenile idiopathic arthritis and Adult onset Still s disease) or with MAS in Systemic lupus erythematous (EMERALD)
The aim of this study is to investigate how safe, effective, and well-tolerated multiple infusions of the experimental study treatment, Emapalumab, are in controlling macrophage activation syndrome (MAS), as well as to check the concentrations of Emapalumab in the blood and the speed at which it leaves the body. Participants will have been treated with previous treatment for MAS and are presenting an unsatisfactory response to that treatment. The previous drugs should include at least the corticosteroids. Your study doctor will taper corticosteroid progressively when emapalumab treatment would be started.
Bryce Binstadt
All
6 Months to 80 Years old
Phase 3
STUDY00013755
STUDY00013755
Inclusion criteria Run-in phase in all cohorts
Informed consent provided by the subject or by the subject s' legally authorized representative(s) with the assent of subjects who are legally capable of providing it, as required by local law.
Male and female subjects aged between 6 months and 80 years of age at the time of diagnosis of MAS.
MAS defined as per the criteria defined below for each cohort and requiring treatment with GCs.
Interventional phase in all cohorts
Informed consent provided by the subject or by the subject's legally authorized representative(s) with the assent of subjects who are legally capable of providing it, as as required by local law.
Male and female subjects aged between 6 months and 80 years of age at the time of diagnosis of active MAS.
Subjects who have shown an inadequate response to high dose intravenous (i.v.) GCs administered for at least 3 days according to local standard clinical practice, including but not limited to pulses of 30 mg/kg PDN on 3 consecutive days. High i.v. GCs dose is recommended not to be lower than 2 mg/kg/ day PDN equivalent (or at least 60 mg/day in pediatric subjects of 30 kg or more, and at least 1g/day in adult MAS subjects). In case of rapid worsening of the subject's condition and/or laboratory parameters, as per Investigator judgment, inclusion may occur within less than 3 days from starting high dose GCs.
Diagnosis of active MAS confirmed by the treating rheumatologist, having ascertained the followings:
a. Febrile subjects presenting with ferritin > 684 ng/mL. b. and any 2 of: i. Platelet count ≤ 181 x109/L ii. AST-level > 48 U/L iii. Triglycerides > 156 mg/dL iv. Fibrinogen level ≤ 360 mg/dL
Female subjects of child-bearing potential willing to use highly effective methods of contraception from study drug initiation to 6 months after the last dose of study drug.
Specific inclusion criteria to Cohort 1 and Cohort 2
Cohort 1:
Confirmed sJIA diagnosis. For subjects presenting with MAS in the context of the onset of sJIA, high presumption of sJIA will suffice for eligibility.
Confirmed diagnosis of AOSD as per Yamaguchi criteria.
Cohort 2:
Confirmed diagnosis of SLE as per SLICC'12 criteria.
Exclusion criteria
Primary HLH documented by either the presence of a known causative genetic mutation or abnormal perforin expression and CD107a degranulation assay as described with primary hemophagocytic lymphohistiocytosis or by the presence of family history.
Confirmed malignancy. Note: subjects with a suspected malignancy should have mononuclear cells typed by flow cytometry and/or tissue biopsy, as applicable, to rule out malignancy.
Treatment with canakinumab, JAK inhibitors, TNF inhibitors and tocilizumab at the time of emapalumab initiation.
Ongoing treatment with anakinra at a dose above 4 mg/kg at time of emapalumab initiation.
Subjects treated with etoposide for MAS in the last 1 month.
Clinically active mycobacteria (typical and atypical), Histoplasma Capsulatum, or Salmonella infections.
Evidence of leishmania infections.
Evidence of latent tuberculosis.
History of hypersensitivity or allergy to any component of the study drug.
Receipt of a Bacillus Calmette-Guerin (BCG) vaccine within 12 weeks prior to screening.
Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to screening.
Pregnancy or lactating female subjects.
Emapalumab, Emapalumab
Macrophage Activation Syndrome, Secondary Hemophagocytic Lymphohistiocytosis, Still Disease, Systemic Lupus Erythematosus, SJIA, AOSD, MAS
A Parallel-group, Two-staged, Phase 2/3, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of REC-2282 in Participants with Progressive NF2 Mutated Meningiomas (POPLAR-NF2)
This study will investigate the efficacy and safety of REC-2282 in patients with progressive NF2 mutated meningiomas who have either NF2 disease-related meningioma or recurrent sporadic meningiomas that have NF2 mutations. This study is a parallel-group, two-staged, Phase 2/3, randomized, multi-center study with two cohorts: Cohort A followed by Cohort B. The purpose of Cohort A is to provide early data on efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas, and provide guidance for the correct dose, population, sample size, and endpoint for the confirmatory part of the study (Cohort B). Additional goals for Cohort A are to assess effects of food on drug absorption. The purpose of Cohort B of the study is to assess the efficacy and safety of REC-2282 compared with placebo in participants with progressive NF2 mutated meningiomas.
Christopher Moertel, MD
All
12 Years to old
Phase 2/Phase 3
STUDY00015488
STUDY00015488
Inclusion Criteria:
≥12 years of age and weighing at least 40 kg
Progressive meningioma that is amenable to volumetric analysis
Has either 1) sporadic meningioma with confirmed NF2 mutation; or, 2) confirmed diagnosis of NF2 disease (revised Manchester criteria); or, 3) at least one NF2-related tumor (with pathogenic germline or proven mosaic NF2 variant)
Adequate bone marrow function
Has provided written informed consent/assent to participate in the study
Exclusion Criteria:
Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months.
Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 6 months prior to screening.
Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening.
History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence.
Received another investigational drug within 30 days prior to screening
Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dose of IMP. REC-2282, Placebo, REC-2282, Placebo
Neurofibromatosis Type 2
Neurofibromatosis Type 2, Neurofibromatosis Type II
A Phase 2/3, prospective, open-label trial evaluating the efficacy, safety, and pharmacokinetics of remimazolam for intravenous sedation in paediatric patients undergoing diagnostic and/or therapeutic procedures
To assess the efficacy of intravenous (IV) remimazolam in inducing and maintaining suitable sedation levels for paediatric patients undergoing diagnostic and/or therapeutic procedures
Kumar Belani
All
0 Years to 17 Years old
Phase 2/Phase 3
STUDY00012859
STUDY00012859
Inclusion Criteria:
Signed informed consent form and/or assent and willingness of patient and parent(s) to participate in the trial.
In US sites: Paediatric male or female patients, aged ≥3 and <18 years scheduled to undergo a diagnostic or therapeutic procedure, which is medically indicated and independent from the trial.
In European sites: Paediatric male or female patients, aged full term birth to <18 years scheduled to undergo a diagnostic or therapeutic procedure, which is medically indicated and independent from the trial.
Maximum planned duration of procedure: 2 hours
ASA Physical Status I-III
Planned spontaneous breathing during sedation
A female who is of child bearing potential (i.e. after menarche) and sexually active must use a highly effective method of birth control during the trial period (from the time of consent until all specified observations are completed)
Negative pregnancy test at screening and on treatment day -
Exclusion Criteria:
Emergency procedures
Condition/procedure that requires planned airway control via endotracheal tube or LMA/IGEL insertion
Cranio-facial malformation, which would severely limit the possibilities for emergency airway rescue
Other abnormalities relating to the airway (including large tonsils and anatomical abnormalities of upper airway or lower airway) which may compromise emergency airway rescue
Known hypersensitivity to benzodiazepines, flumazenil, dextran or any of the ingredients of the drug product
Known paradoxical reactions to benzodiazepines
History of sleep apnoea
Active respiratory failure
Active neuromuscular disease
Active cardiac failure
Active hepatic failure
Breast feeding females
Prohibited medication
Any patient judged by the Principal Investigator (PI) or Sub-Investigator to be inappropriate for the trial for any other reason Remimazolam, Remimazolam
Pediatric ALL
Choline Supplementation as a Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorders Study (CHOLINE4)
This is a double-blind randomized placebo-controlled clinical trial examining choline supplementation in 2-5 year old children with Fetal Alcohol Spectrum Disorders. Outcome measures are neurocognitive tests of memory, attention, and behavior.
Jeffrey Wozniak
All
30 Months to 72 Months old
Phase 2
1506M74642
1506M74642
Inclusion Criteria:
Ages 2.5 years to 5 years old (<6 years of age) at enrollment
Prenatal alcohol exposure
Available parent or legal guardian capable of giving informed consent for participation.
Exclusion Criteria:
History of a neurological condition (ex. epilepsy, traumatic brain injury)
History of a medical condition known to affect brain function
Other neurodevelopmental disorder (ex. autism, Down syndrome)
History of very low birthweight (<1500 grams) Choline Bitartrate, Choline Bitartrate
Fetal Alcohol Spectrum Disorders
SPR001-205 A Phase 2 Study to Evaluate the Safety, Pharmacokinetics, and Exploratory Pharmacodynamics of SPR001 (Tildacerfont) in Children Aged 6 to 17 Years with Congenital Adrenal Hyperplasia
This is a Phase 2, open-label, multiple-dose study designed to provide safety, PK, and exploratory PD data for tildacerfont in male and female children aged 6 to 17 years with CAH. The study will last approximately 10 weeks including Screening. After the 14-day Treatment Period, there will be a Safety Follow-up Visit 30 days after the last dose.
Kyriakie Sarafoglou
All
2 Years to 17 Years old
Phase II
STUDY00014680
STUDY00014680
Inclusion Criteria:
Male and female subjects aged 2 to 17 years
Diagnosis of CAH due to 21-hydroxylase deficiency (OHD) and/or elevated 17- hydroxyprogesterone (OHP) requiring ongoing GC replacement since diagnosis
Stable dose of GC replacement for at least 1 month prior to screening
Exclusion Criteria:
CAH not due to 21-OHD
History of bilateral adrenalectomy or hypopituitarism
Clinically significant unstable medical conditions, illness, or chronic diseases
History of active bleeding disorders
Females who are pregnant or nursing Tildacerfont, Tildacerfont
Rare Diseases
Adrenal Disorder, CAH, Congenital Adrenal Hyperplasia, Pediatric
Identifying body awareness-related brain network changes during cognitive multisensory rehabilitation for reduced neuropathic pain in people with spinal cord injury
This mechanistic Phase II clinical trial will utilize a design with a standard parallel-arm RCT. Participants will be randomized into two groups. The Immediate Therapy Group will receive 6 weeks of CMR, 1-on-1, in-person, 3x/week, 45 min/sessions immediately, followed by 6 weeks of standard of care (no therapy) at home as a monitoring/observation period. And the Delayed Therapy Group will first complete the monitoring/observation period with 6 weeks of standard of care (no therapy) at home, followed by 6 weeks of CMR. The healthy group will not receive therapy. The baseline data obtained in the healthy control group will be compared with the baseline data and post-CMR data in both SCI groups.
Ann Van de Winckel
All
18 Years to 70 Years old
N/A
STUDY00008476
STUDY00008476
Inclusion Criteria:
SCI participants:
SCI of ≥ 3months
medically stable with paraplegia (ASIA grade A-C, who can self-transfer with some assistance)
neuropathic pain (>3 on the numeric pain rating scale)
Able-bodied participants:
sex and age matched
healthy, able-bodied
Exclusion Criteria:
• MRI contra-indications (stabilizing hardware is typically MRI safe) including seizures, cognitive impairment, or other major medical complications
Cognitive Multisensory Therapy, Usual Care, Clinical Assessment, Magnetic Resonance Imaging (MRI), OPTIONAL: blood draw, Cognitive Multisensory Therapy, Usual Care, Clinical Assessment, Magnetic Resonance Imaging (MRI), OPTIONAL: blood draw
Spinal Cord Injuries, Neuropathic Pain
MT2017-28 The Head Start 4 Protocol - Newly Diagnosed Children (less than 10 years old) with Medulloblastoma and Other Central Nervous System Embryonal Tumors: Clinical and Molecular Risk-Tailored Intensive and Compressed Induction Chemotherapy Followed by Consolidation with Either Single Cycle (Low Risk Patients) or Randomization (High Risk Patients) to Either Single-Cycle or to Three Tandem Cycles of Marrow-Ablative Chemotherapy with Autologous Hematopoietic Progenitor Cell Rescue Added Title: Neuroanatomical, Cognitive and Family Aspects to Recovery from a Brain Tumor
Christopher Moertel, MD
All
to 10 Years old
Phase 4
STUDY00000427
STUDY00000427
Inclusion Criteria:
Patients 10 years of age at the time of definitive confirmatory eligible histologic or cytologic diagnosis of eligible CNS tumor (brain or spinal cord)
Patients may not have received irradiation or chemotherapy (except corticosteroids)
Have histologically proven diagnosis of medulloblastoma or CNS embryonal tumors of the brain or spinal cord
Medulloblastoma
Posterior fossa classic, desmoplastic or extensive nodular or anaplastic/large cell medulloblastoma with appropriate and sufficient tumor material (FFPE or snap frozen) for proposed assays: all stages, age less than 6 years at diagnosis
Posterior fossa classic or anaplastic/large cell medulloblastoma with sufficient tumor material (FFPE or snap frozen) for proposed assays: clinically high-stage (neuraxis or extra-neural dissemination, M1-4), age greater than 6 years to less than 10 years at diagnosis
Posterior fossa medulloblastoma, those 6 years of age and above at diagnosis, will only be eligible if they have evidence of neuraxis or extraneural dissemination. Patients 6 years of age and above with low-stage (standard-risk, M0) medulloblastoma will NOT be eligible for this study, irrespective of molecular subgroup and extend of local resection
CNS Embryonal Tumors:
• Pineoblastoma, CNS neuroblastoma, CNS ganglioneuroblastoma, embryonal tumor with multi-layered rosettes (ETMR, including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI1 intact) and CNS embryonal tumor, not otherwise specified. Must commence Induction chemotherapy within 28 days of the most recent definitive surgical procedure and within 21 days of the most recent neuro-imaging studies (MRI of brain, performed with and without gadolinium contrast, and MRI of total spine, performed with gadolinium contrast) and lumbar CSF cytological examination Patients must have adequate organ functions at the time of registration: Liver: bilirubin less than 1.5 mg/dL (except for patients with Gilbert's Syndrome of indirect hyperbilirubinemia) and transaminases [SGPT or ALT, and SGOT or AST] less than 2.5 (two and a half) times the upper limits of institutional normal. Renal: Creatinine clearance and/or glomerular filtration rate (GFR) greater than or equal to 60 mL/min/1.73m² within 21 days of protocol therapy. Bone Marrow Function: Peripheral absolute phagocyte count (APC) > 1000/ µL. APC = numbers of banded neutrophils + segmented neutrophils + metamyelocytes + monocytes + eosinophils Please note, if institution reports differential as a percentage, then APC = [percentage of banded neutrophils + segmented neutrophils+ metamyelocytes+monocytes+eosinophils] x total white cell count. Platelet Count > 100,000/µL (transfusion independent) Hemoglobin > 8 gm/dL (may have received RBC transfusions).
Exclusion Criteria:
Patients older than 10 years of age at time of diagnosis
Following diagnoses are not eligible for study enrollment: CNS atypical teratoid/rhabdoid tumor (AT/RT); all ependymomas including anaplastic ependymomas of the brain or spinal cord; all choroid plexus carcinomas; all high-grade glial and glio-neuronal tumors; all primary CNS germ cell tumors; all primary CNS sarcomas; all primary or metastatic CNS lymphomas and solid leukemic lesions (i.e., chloromas, granulocytic sarcomas).
Patients with unbiopsied diffuse intrinsic pontine tumors will NOT be eligible for this study. Induction, Single Cycle Intensive Chemotherapy, Tandem 3 Cycle Intensive Chemotherapy, Induction, Single Cycle Intensive Chemotherapy, Tandem 3 Cycle Intensive Chemotherapy
Medulloblastoma, Central Nervous System Embryonal Tumors