Search Results
Telehealth study assessing the removal of filter ventilation on smoking behavior and biomarkers
This single-blind, between-subject, randomized, multi-center study will assess the effect of cigarettes with unventilated vs. ventilated filters on smoking behavior and biomarkers of tobacco toxicant exposure. The study uses telehealth and brief in-clinic or curbside visits and will also examine the feasibility of remote collection of multiple biological samples. Subjective measures, alveolar carbon monoxide, blood pressure and cigarettes per day will be collected remotely. Biological samples collected at home will be dropped off at the clinic at a brief clinic or curbside visit where the study cigarettes will be dispensed. Smokers using conventional cigarette brands with filter ventilation of about 16-36% will enter a three phase study. Phase 1 is a 1-week baseline period of smoking usual brand cigarettes; Phase 2 consists of 2 weeks of smoking ventilated cigarettes; and Phase 3 where subjects are randomly assigned to one of two conditions: 1) ventilated cigarettes; or 2) unventilated cigarettes smoked for a 6 week period. Weekly telehealth visits are conducted to collect study measures and subjects attend a brief clinic or curbside visits to pick up study cigarettes and drop off biomarker samples. A follow-up telehealth visit will occur at one-month post intervention.
MT2019-47 Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered NY-ESO-1-Specific (c259) T Cells, alone or in combination with other agents, in HLA-A2+ Participants with NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (IGNYTE-ESO) Protocol Number: 208467
This is a master protocol to investigate the safety and antitumor activity of T-cell receptor (TCR) engineered NY-ESO-1 Specific (c259) T Cells alone or in combination with other agents in HLA-A*02+ participants with NY-ESO-1 and/or LAGE-1a positive solid tumors. The protocol will initially include a substudy to investigate letestregene autoleucel (lete-cel, GSK3377794) treatment in previously untreated (1L) HLA-A*02+ participants with NYESO-1+ advanced (metastatic or unresectable synovial sarcoma or myxoid/round cell liposarcoma (Substudy 1). A separate substudy will investigate letestregene autoleucel (lete-cel, GSK3377794) infusion as second line or higher (2L+) treatment in HLA-A*02+ participants with NY-ESO-1+ advanced metastatic or unresectable synovial sarcoma or myxoid/round cell liposarcoma, who have progressed following treatment with anthracycline based chemotherapy for the purpose of registration (Substudy 2). The protocol may be amended at a later time to add additional substudies to investigate other NY-ESO-1 or LAGE-1a positive tumor types and other NY-ESO-1-Specific (c259) T Cells (potentially in combination with other agents).
Alport Syndrome Treatments and Outcomes Registry (ASTOR)
The Alport Syndrome Treatments and Outcomes Registry (ASTOR) was founded in 2007 with the goal of facilitating clinical trials of new treatments for the disease. Because Alport syndrome is a rare disorder, rapid recruitment of sufficient participants for meaningful therapeutic trials will be greatly enhanced by pre-existing patient registries.
HYDROXYCHLOROQUINE (HCQ) FOR PREVENTION OF ABNORMAL GLUCOSE TOLERANCE AND DIABETES IN RELATIVES AT-RISK FOR TYPE 1 DIABETES MELLITUS (Protocol TN-22) (TN-22)
The study is a 2-arm, double blinded, multicenter, 2:1 randomized, placebo-controlled clinical trial. All participants will receive close monitoring for progression of T1D. Participants will receive hydroxychloroquine or placebo and close monitoring for progression to Stage 2 (abnormal glucose tolerance) or Stage 3 (clinically overt) T1D. To assess the efficacy, safety and mode of action of hydroxychloroquine to prevent progression from Stage 1 to Stage 2 or Stage 3 of T1D.
• Participant in TrialNet Pathway to Prevention Study (TN01)
• Age 3 years or greater at the time of randomization
• Willing to provide informed consent
• Normal glucose tolerance by OGTT within 7 weeks (no more than 52 days) of baseline
• Two or more diabetes-related autoantibodies present on two separate samples
• Weight of 12 kg or greater at screening
• If a female participant with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing prior to randomization and at each study visit
• Anticipated ability to swallow study medication.
• Abnormal Glucose Tolerance or Diabetes
• History of treatment with insulin or other diabetes therapies
• Ongoing use of medications known to influence glucose tolerance
• Ongoing or anticipated future use of medications known to have untoward interactions with hydroxychloroquine
• Known hypersensitivity to 4-aminoquinoline compounds
• G6PD deficiency
• History of retinopathy
• Have an active infection at time of randomization
• Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B core antibody or surface antigen), or Hepatitis C infection
• Deemed unlikely or unable to comply with the protocol or have any complicating medical issues, including prolonged QT interval, a disease previously or likely in the future to require immunosuppression, or abnormal clinical laboratory results that interfere with study conduct or cause increased risk.
• Deemed unlikely or unable to comply with the protocol or have any complicating medical issues, including prolonged QT interval, a disease previously or likely in the future to require immunosuppression, or abnormal clinical laboratory results that interfere with study conduct or cause increased risk.
• Be pregnant or breastfeeding.
A LONG-TERM, OPEN-LABEL STUDY TO EVALUATE THE SAFETY, PHARMACODYNAMICS, AND EFFICACY OF MIGALASTAT IN SUBJECTS > 12 YEARS OF AGE WITH FABRY DISEASE AND AMENABLE GLA VARIANTS
This an extension study assessing the use of migalastat (AT1001) in pediatric populations. AT1001, under the trade name Galafold, is approved for use in the US in adults, but not children. The parent study is approved by the IRB under STUDY00006216.
• Male or female subjects diagnosed with Fabry disease > 12 years of age who completed Study AT1001-020
• Subject's parent or legally-authorized representative is willing and able to provide written informed consent and authorization for use and disclosure of personal health information or research-related health information, and subject provides assent, if applicable
• Subject's parent or legally-authorized representative is willing and able to provide written informed consent and authorization for use and disclosure of personal health information or research-related health information, and subject provides assent, if applicable
• Has moderate or severe renal impairment (eGFR <60 ml/min/1.73 m2 at screening)
• Has advanced kidney disease requiring dialysis or kidney transplantation
• History of allergy or sensitivity to study medication (including excipients) or other iminosugars (eg, miglustat, miglitol)
• Has received any gene therapy at any time or anticipates starting gene therapy during the study period
• Requires treatment with Glyset (miglitol), Zavesca (miglustat) within 6 months before screening or throughout the study
• Requires treatment with Replagal (agalsidase alfa), or Fabrazyme (agalsidase beta) within 14 days before screening or throughout the study
• Subject is treated or has been treated with any investigational/experimental drug, biologic or device within 30 days before screening
• Any intercurrent illness or condition or concomitant medication use considered to be a contraindication at screening or baseline or that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the potential subject may have an unacceptable risk by participating in this study
• Pregnant or breast-feeding
• Otherwise unsuitable for the study in the opinion of the investigator
Assessment of the impact of transcatheter stenting of aortic coarctation on the left ventricular afterload and work using left ventricular pressure volume loops
The purpose of this study is to understand the effects of stent therapy of coarctation of the aorta on the left ventricular afterload and mechanics by obtaining intracardiac pressures and volume using a special P-V loop catheter system.
• Children 6 years of age and older and adults of all races and both sexes referred for elective cardiac catheterization and stent therapy for coarctation
• Those who provide informed consent for study participant.
• Children who undergo other interventions in addition to the coarctation
• Children with single ventricle physiology.
• Renal impairment
• Participant unwilling to sign a consent form.
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)
Phase II Multicenter, Randomized, Double-Blind, 12-Week Treatment, 3-Arm, Parallel-Group, Placebo-Controlled Study
• 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) genetically defined ASD per genetic results available prior to screening or known "syndromic" forms of ASD (e.g., fragile X syndrome, Prader Willi syndrome, Rett's syndrome, or tuberous sclerosis).
• 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
Combined Cortical and Striatal Stimulation for Re-Regulating Circuits of Obsessive-Compulsive Disorder
The purpose of this investigation is to obtain a preliminary indication of the feasibility, safety and efficacy of combined cortical and subcortical stimulation and recording for treatment-resistant OCD.
A STUDY EVALUATING THE PREGNANCY OUTCOMES AND SAFETY OF INTERRUPTING ENDOCRINE THERAPY FOR YOUNG WOMEN WITH ENDOCRINE RESPONSIVE BREAST CANCER WHO DESIRE PREGNANCY (POSITIVE)
Electronic Platform for Assessment of Adherence, Quality of Life, Clinical Response and Safety of Daily and Long‐Acting Growth Hormone Therapy (LAuGH TRACK UMN) (LAuGH TRACK)
The purpose of the study is to compare quality of life (QOL), adherence, insulin resistance, body composition and efficacy of LAGH to DGH in children with GHD.
• Girls must be between the ages of 2 and 11 years, and boys must be between the ages of 2 and 13 years
• Have established diagnosis of pediatric growth hormone deficiency (GHD). For the purposes of the study, GHD is defined as peak growth hormone response to clonidine/arginine stimulation testing of <10 ng/mL
• Either treatment-naive or currently treated with a daily growth hormone as approved by health insurance
• Any medical condition which, in the opinion of the Investigator, can be an independent cause of short stature and/or limit the response to exogenous growth factor treatment
• Current treatment with long-acting growth hormone
• Currently pregnant or breastfeeding
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Adult Subjects with Classic Congenital Adrenal Hyperplasia
Study SPR001-203 will be a larger, randomized, double-blind, placebo-controlled, dose-ranging study that will investigate the efficacy and safety of up to 52 weeks of treatment with tildacerfont in subjects with classic CAH who have elevated biomarkers at baseline (A4 >1.5x upper limit of normal [ULN] and ACTH >2x ULN) on their current Glucocorticoid regimen.
Understanding the long term impact of COVID-19 on the brain by advanced MR imaging and spectroscopy
In this study, we want to learn more about what kinds of structural and chemical changes are happening in the nervous systems of people recovering from COVID-19 compared to people who have not been exposed to COVID-19.
• Participants must be 18 years or older
• Participants must fall into one of the following groups: a) no known COVID-19 exposure (for controls), or b) laboratory confirmed COVID-19 who present with neurological symptoms in the months after infection and were either 1) non-hospitalized, or 2) hospitalized, but never underwent invasive (tube in throat) ventilation
• Participants must be English or Spanish speaking
• Participants must be able to provide written informed consent
• Participants must be clear of any contraindications for MRI (see exclusions) *Study not registered on Clinicaltrials.gov
• Medical conditions likely to interfere with the study, including chronic neurologic conditions (such as Alzheimer disease, Parkinson's disease, ALS, HIV-Associated Neurocognitive Disorder, brain infections, or brain tumors), traumatic brain injury with loss of consciousness, end-stage kidney disease, end-stage liver disease, restless leg syndrome, chronic lung disease unrelated to COVID-19 needing oxygen, history of stroke unrelated to COVID-19, history of bipolar disorder or psychotic illness (such as schizophrenia or schizoaffective disorder)
• Individuals who had COVID-19 and required mechanical invasive ventilation
• Pregnant women
• Inability to undergo MRI scanning, including but not limited to claustrophobia, unable to remain still in an MRI scanner for more than 30 minutes, presence of metallic foreign bodies or pacemakers in body, weight over 350 lbs. *Study not registered on Clinicaltrials.gov
VX20-121-102: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-121 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for F508del and a Minimal Function Mutation (F/MF)
This is a Phase 3, randomized, double-blind, ELX/TEZ/IVA-controlled, parallel-group, multicenter study to evaluate the efficacy of VX-21/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in cystic fibrosis (CF) subjects who are heterozygous for F508del and a minimal function mutation (F/MF subjects).
• Heterozygous for F508del and a minimal function mutation (F/MF genotype)
• Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean for age, sex, and height for participants currently receiving ELX/TEZ/IVA therapy; FEV1 >=40% and <=80% for participants not currently receiving ELX/TEZ/IVA Key
• History of solid organ or hematological transplantation
• Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
• Lung infection with organisms associated with a more rapid decline in pulmonary status
• Pregnant or breast-feeding females Other protocol defined Inclusion/Exclusion criteria may apply
A Randomized, Double-Blind, Multicenter, Placebo-Controlled Phase 3 Study with Open-Label Period to Evaluate the Efficacy and Safety of Inebilizumab in Adults with Myasthenia Gravis
This is a randomized, double-blind, placebo-controlled, parallel-group study with an optional open-label extension testing the safety and efficacy of inebilizumab in participants with Myasthenia Gravis.
S1418/BR006, A Randomized, Phase III Trial to Evaluate the Efficacy and Safety of MK-3475 as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer with > 1 cm Residual Invasive Cancer or Positive Lymph Nodes (>pN1mic) After Neoadjuvant Chemotherapy
MT2010-09 Primary Immune Deficiency Treatment Consortium (PIDTC). PROJECT 1: A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children with SCID Disorders (RDCRN PIDTC #6901)
• Absence or very low number of T cells (CD3 T cells <300/microliter) AND
• No or very low T cell function (<10% of lower limit of normal) as measured by response to phytohemagglutinin (PHA) OR
• T cells of maternal origin present. Stratum B: Leaky SCID, Omenn Syndrome, Reticular Dysgenesis- -Subjects who meet the following criteria and the intention is to treat with HCT are eligible for enrollment into Stratum B: Leaky SCID:
• Maternal lymphocytes tested for and not detected AND
• Either one or both of the following (a,b) :
• a.) <50% of lower limit of normal T cell function as measured by response to PHA, OR response to anti-CD3/CD28 antibody
• b.) Absent or <30% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens
• AND at least two of the following (a through e):
• a.) Reduced number of CD3 T cells
• age ≤2 years: <1500/microliter
• age >2 years and ≤4 years: <800/microliter
• age >4 years: <600/microliter
• b.) ≥80% of CD3+ or CD4+ T cells that are CD45RO+
• AND/OR >80% of CD3+ or CD4+ T cells are CD62L negative
• AND/OR >50% of CD3+ or CD4+T cells express HLA-DR (at <4 years of age)
• AND/OR are oligoclonal T cells
• c.) Hypomorphic mutation in IL2RG in a male, or homozygous hypomorphic mutation or compound heterozygosity with ≥1 hypomorphic mutation in an autosomal SCID-causing gene
• d.) Low T Cell Receptor Excision Circles (TRECs) and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal.
• e.) Functional testing in vitro supporting impaired, but not absent, activity of the mutant protein, AND
• Does not meet criteria for Omenn Syndrome. Omenn Syndrome:
• Generalized skin rash
• Maternal lymphocytes tested for and not detected; --Note: If maternal engraftment was not assessed and ruled out, the subject is not eligible as Omenn Syndrome.
• ≥80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR
• 80% of CD3+ or CD4+T cells are CD62L negative AND/OR
• 50% of CD3+ or CD4+ T cells express HLA-DR (at <2 years of age);
• Absent or low (< 30% lower limit of normal) T cell proliferation response to antigens (Candida, tetanus) to which the subject has been exposed NOTE: If proliferation to antigen was not performed, but at least 4 of the following 9 supportive criteria, at least one of which must be among those marked with an asterisk (*) below are present, the subject is eligible as Omenn Syndrome:
• Hepatomegaly
• Splenomegaly
• Lymphadenopathy
• Elevated IgE
• Elevated absolute eosinophil count
• *Oligoclonal T cells measured by CDR3 length or flow cytometry
• *Proliferation to PHA is reduced <50% of lower limit of normal or SI <30
• *Hypomorphic mutation in a SCID causing gene
• Low TRECS and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal. Reticular Dysgenesis:
• Absence or very low number of T cells (CD3 <300/µL
• No or very low (<10% lower limit of normal) T cell response to PHA
• Severe neutropenia (absolute neutrophil count < 200 /µL) AND
• ≥2 of the following (a,b,c):
• a.) Sensori-neural deafness
• b.) Deficiency of marrow granulopoiesis on bone marrow examination
• c.) A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified. Stratum C: Subjects who meet the following criteria and the intention is to treat with therapy other than allogeneic HCT, primarily PEG-ADA ERT or gene therapy with autologous modified (gene transduced) cells, are eligible for enrollment into Stratum C:
• ADA Deficient SCID with intention to treat with PEG-ADA ERT
• ADA Deficient SCID with intention to treat with gene therapy
• X-linked SCID with intention to treat with gene therapy
• Any SCID patient previously treated with a thymus transplant (includes intention to treat with HCT, as well as PEG-ADA ERT or gene therapy)
• Any SCID patient who received therapy for SCID deemed "non-standard" or "investigational", including in utero procedures.
• Presence of an Human Immunodeficiency Virus (HIV) infection (by PCR) or other cause of secondary immunodeficiency
• Presence of DiGeorge syndrome
• MHC Class I and MHC Class II antigen deficiency, and
• Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency or transcobalamin deficiency.
Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial (CLASP II TR): A prospective, multicenter, randomized, controlled pivotal trial to evaluate the safety and effectiveness of transcatheter tricuspid valve repair with the Edwards PASCAL Transcatheter Valve Repair System and optimal medical therapy (OMT) compared to OMT alone in patients with tricuspid regurgitation
This is a prospective, multicenter, randomized, controlled pivotal trial to compare the safety and effectiveness of the PASCAL System and OMT to OMT alone for patients with symptomatic severe tricuspid regurgitation.
Vibrotactile stimulation of the larynx to treat unexplained chronic cough
This is a study of adults with unexplained chronic cough between 18-80 years old. This study is trying to determine whether a noninvasive vibrotactile stimulation device can help reduce cough symptoms.
Distal Evaluation of Functional performance with Intravascular sensors to assess the Narrowing Effect: Guided Physiologic Stenting
A multi-center, prospective, randomized controlled study employing an adaptive design study for interim sample size re-estimation. Objectives: -Demonstrate that PCI guided by iFR Co-registration is associated with superior clinical outcomes compared to PCI guided by angiography alone -To evaluate the cost-effectiveness of physiology guidance with SyncVision compared to a standard of care PCI strategy -To establish the relationship between physiological guidance and improvement in associated angina and quality of life scores -To examine the outcomes in patients in whom an optimized post-PCI iFR can versus cannot be achieved
Clinical and Basic Investigations into Congenital Disorders of Glycosylation
Define natural history, validate patient reported outcome and share knowledge on congenital disorders of glycosylation. We will recruit and enroll patients with CDG in this study evaluating clinical variation and natural history when a patient is being seen as part of routine clinical care.
• Patients diagnosed with congenital disorders of glycosylation based on genetic confirmatory testing
• Patients without congenital disorders of glycosylation
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Reducing Supraphysiologic Glucocorticoid Use in Adult Subjects with Classic Congenital Adrenal Hyperplasia
SPR001-204 will be a randomized, double-blind, placebo-controlled study that will evaluate the potential of tildacerfont to reduce GC burden in adult subjects with classic CAH who have lower limit of detection (LLD) ≤ A4 ≤ 1.5x upper limit of normal (ULN) and are on supraphysiologic doses of GC therapy. SPR001-204 will be the first study of tildacerfont to evaluate GC dose reduction. In addition, Study SPR001-204 will characterize clinical outcomes after up to 52 weeks of treatment with tildacerfont.
A novel Peptamen-based enteral nutrition protocol for treatment of Crohn s disease A Pilot Trial
The purpose of this study is to evaluate the therapeutic feasibility of a Peptamen-based, oral nutrition dietary regimen for treatment of adult Crohn’s disease. Specifically we are evaluating if consuming 80-100% of caloric needs from Peptamen 1.5 for 4 weeks is feasible for the potential future use therapeutically in adult Crohn’s disease.
APOL1 Long-term Kidney Transplantation Outcomes Network
The National Institutes of Health (NIH)-sponsored collaborative APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is charged with prospectively assessing the effects of renal-risk variants (RRVs) in the apolipoprotein L1 gene (APOL1) on outcomes for kidneys from donors with recent African ancestry and the recipients of their kidneys, after deceased- and living-donor renal transplantation. For the purposes of APOLLO, recent African ancestry is defined as individuals with similar genetic make-up to those currently residing in Africa. APOLLO will also study the impact of APOL1 RRVs on the health of living kidney donors with recent African ancestry.
The REPLACE Registry
This is a prospective, observational, non-interventional patient registry designed to document product safety and clinical outcomes for 10 years in patients treated with Cholbam/Kolbam, including those who have been using Cholbam/Kolbam for at least one month (existing users) and those who start Cholbam/Kolbam treatment at enrollment (new users). Patients who have been using Cholbam/Kolbam for less than one month and those who had previously been treated and who restart treatment will also be included but will not be counted in the existing or new users groups.
• Male and female patients, of any age.
• The patient and/or the patient's parent/legal guardian is willing and able to provide signed informed consent, and the patient, if less than 18 years of age, is willing to provide assent as appropriate and in accordance with local regulatory, IRB, and EC requirements.
• The patient has a diagnosis for which Cholbam is indicated.
• The patient is or will be treated with Cholbam at the time of signing the informed consent form (ICF) (enrollment).
• Patients who, by judgement of the Investigator, will not be able to comply with the requirements of the protocol will be excluded
An Assessment of the Biological and Clinical Effects of Palbociclib (PD 0332991) with Ovarian Suppression and Letrozole in the Neoadjuvant Treatment of Patients with Premenopausal Estrogen-Receptor Positive/ HER2-Negative Primary Breast Cancer
This cross-sectional study will use different modes of survey administration to examine how the level of harm patients sustain due to a medical error or adverse event influences Minnesota physicians' willingness to disclose them to patients and/or their families. A random sample of 8,000 currently licensed physicians will be selected from the state licensure database to participate in this study.
STUDY OF PHIL?? EMBOLIC SYSTEM IN THE TREATMENT OF INTRACRANIAL DURAL ARTERIOVENOUS FISTULAS
Arteriovenous fistulas are a type of arteriovenous malformation whereby blood is shunted directly from the arterial system to the venous system, bypassing the capillary bed. Dural arteriovenous fistulas (dAVFs) are a rare type of acquired intracranial vascular malformation consisting of a pathologic shunt located within the dura mater of the brain. 1 These lesions have been categorized by Awad et al 2, Borden et al 3, and Cognard et al 4 according to their locations and patterns of venous drainage. Dural arteriovenous fistulas (dAVFs) can be observed anywhere on the dural layer meninges of the cranium and spine. This condition accounts for 10-15% of all intracranial arteriovenous malformations diagnosed. 5 These fistulas can be congenital or acquired diseases. When observed as acquired diseases, they are most often encountered in males between the age of 50 and 60 years old. DAVFs present with a wide spectrum of symptoms or none at all, and come with varying range of risk of clinical sequalae. A thorough evaluation of the anatomy and venous drainage is crucial to determining the best treatment strategy. Acute presentation with intracranial hemorrhage occurs in up to 65% of patients, and patients with a previous intracranial hemorrhage may have up to a 35% risk of another neurologic event within 2 weeks. 6 Endovascular embolization has become the primary treatment approach for DAVFs. The goal of endovascular therapy is to achieve complete obliteration of the fistulous point between the feeding arteries and the draining veins. This can be safely accomplished by occluding the draining veins, which often results in complete closure of the lesion, unlike in cerebral arteriovenous malformations. The PHIL® device is a non-adhesive liquid embolic agent comprised of a Triiodophenol-(lactide-co-glycolide) acrylate and hydroxyethyl methacrylate (HEMA) co-polymer dissolved in DMSO (dimethyl sulfoxide). An iodine component is chemically bonded to the co-polymer to provide a radiopacifier element during fluoroscopic visualization. The PHIL® Liquid Embolic System consists of a sterile, pre-filled, 1.0 mL syringe of PHIL® liquid embolic, a sterile, prefilled 1.0 mL syringe of DMSO, and microcatheter hub adaptors. Intracranial dAVFs may produce a wide variety of symptoms. Individual risk is evaluated by a precise analysis of the venous drainage. The decision to treat is based on this analysis. Treatment strategy is decided by a multidisciplinary neurovascular team and must consider the individual risk of each dAVF. Embolization is, in most cases, proposed as the first treatment option and often succeeds to obtain a complete and definitive cure of the dAVF. Surgery may be required in some locations or in the case of embolization failure. Radiosurgery is rarely indicated because it is not always efficient and because of the time required for shunt obliteration and the risk of bleeding in this period. Liquid embolics have distinct characteristics that make them a principle treatment option in the obliteration of dAVFs. They can flow through complex vascular structures so that the surgeon does not need to target the catheter to every single vessel. 10 There is little choice available in the US market for the liquid embolic treatment of dAVF. Currently, nBCA (TRUFILL n-Butyl Cyanoacrylate, Cordis) and Onyx (Medtronic) are the only liquid embolic agents available. Both are approved by FDA for presurgical embolization of cerebral arteriovenous malformations. However, they have been used off-label for dAVFs. This use demonstrates the unmet medical need for the patients suffering with dAVFs. The aim of this study is to evaluate the use of PHIL in the management of intracranial dural AVFs.
Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (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.
• ≥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
• 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.
Pulmonary Hypertension Association Registry (PHAR) (PHAR)
The PHAR is a multicenter, prospective registry of newly evaluated patients at PHCCs in the United States who have either PAH or CTEPH. The goals of the PHAR include 1) measuring and improving quality of care (including assessing differences in adherence to evidence-based guidelines and establishing benchmarks for health outcomes), 2) determining the clinical effectiveness, comparative effectiveness, and cost effectiveness of treatment approaches, 3) understanding risk factors for outcomes and regional/center differences, and 4) facilitating funded clinical trials of new therapies and collaboration with the PAH community at large, including providers, patients, and their caregivers.
• All age groups
• Written informed consent
• Pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH), or pediatric PH due to developmental lung disease
• Within 6 months of first outpatient visit at a PH Care Center
• Diagnosis of WSPH Group 2 pulmonary hypertension
• Diagnosis of WSPH Group 3 pulmonary hypertension, except PH due to developmental lung disease
• Diagnosis of WSPH Group 5 pulmonary hypertension
A Phase 3, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Healthy Females 16-40 Years of Age (mRNA-1647-P301)
This is a Phase 3, randomized, observer-blinded, placebo-controlled study in healthy participants 16 to 40 years of age. The primary efficacy objective is to demonstrate vaccine effect of mRNA-1647 against primary cytomegalovirus (CMV) infection in female participants who are CMV-seronegative at enrollment.
Phase 3 Multicenter, Double-Blind, Placebo-Controlled Trial of Viralym-M;(ALVR105) for the Treatment of Patients With Virus-Associated Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplant
The study hypothesis is that the administration of Viralym-M to patients with virus-associated HC will demonstrate superiority for the time to resolution of HC (as measured by resolution of macroscopic hematuria) compared to patients treated with placebo. The primary hypothesis will be tested in patients with BKV viruria to demonstrate superiority over placebo in this population (BK Intent-to-Treat [ITT] Population). A supplementary analysis will be conducted in all patients with any viral-associated HC (BKV, JCV, AdV, EBV, CMV, and/or HHV-6) in order to evaluate efficacy in this broader population (ITT Population). Further detail is provided in the statistical section below and will be described in the Statistical Analysis Plan (SAP).
• Male or female ≥1 year of age.
• Had an allogeneic hematopoietic cell transplant (HCT) performed ≥21 days and ≤1 year prior to randomization.
• Myeloid engraftment confirmed, defined as an absolute neutrophil count ≥500/mm³ for 3 consecutive laboratory values obtained on different days, and platelet count >10,000/mm³ at the time of randomization.
• Diagnosed with HC based on the following criteria (all 3 criteria must be met):
• Clinical signs and/or symptoms of cystitis.
• Grade ≥3 hematuria, defined as macroscopic hematuria with visible clots.
• Viruria with ≥1 target virus (ie, BKV, JCV, AdV, CMV, EBV, and/or HHV-6).
• At least 1 identified, suitably matched posoleucel (ALVR105) cell line for infusion is available. Key Exclusion Criteria Participants who meet any of the following criteria will be excluded from participation in the study:
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent).
• Therapy with antithymocyte globulin, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted monoclonal antibodies ≤28 days before randomization.
• Evidence of active Grade >2 acute graft versus host disease (GVHD).
• Uncontrolled or progressive bacterial or fungal infections.
• Uncontrolled or progressive viral infections not targeted by posoleucel (ALVR105).
• Uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder.
• Known or presumed pneumonia secondary to any organism that is not considered to be well-controlled by antimicrobial therapy.
• Pregnant or lactating or planning to become pregnant. Note: Other protocol defined Inclusion/Exclusion criteria may apply.