Search Results
Study of HST5040 in Subjects With Propionic or Methylmalonic Acidemia (HERO)
• 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.
• 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.
A Study of Gene Therapy for Classic Congenital Adrenal Hyperplasia (CAH)
This is a Phase 1/2, first-in-human, open-label, dose-escalation study designed to evaluate the safety, tolerability, and efficacy of BBP-631 administered to up to 25 adult participants diagnosed with classic congenital adrenal hyperplasia (CAH) (simple virilizing or salt-wasting, Group 1) or with classic salt-wasting CAH (Group 2) due to 21-hydroxylase deficiency (21-OHD) and who are monitored for 24 weeks posttreatment.
• Adult male and non-pregnant females with classic CAH (simple virilizing or salt-wasting) due to 21-OHD
• Screening/baseline 17-OHP levels > 5-10 × ULN and < 40 × ULN (upper limit of normal)
• Stable oral hydrocortisone (HC) regimen as the only glucocorticoid (GC) maintenance therapy
• Naïve to prior gene therapy or AAV-mediated therapy Key Exclusion Criteria
• Positive for anti-AAV5 (Adeno-Associated Virus Type 5) antibodies
• History of adrenalectomy and has no significant liver disease
Expansion Cohort Study of Disulfiram and Chemotherapy in Pancreas Cancer Patients
Disulfiram is a potential inhibitor of muscle degradation and may reduce tumor induced muscle wasting. Emerging research also suggests it might have anti-cancer effects. This study examines whether targeting muscle loss with Disulfiram will reverse disability and eventually improve survival in patients with incurable pancreatic cancer. It tests the safety, tolerability and potential benefit of disulfiram (Antabuse®) in combination with chemotherapy
Precision Anesthesia: A Genomics Study of Post Cesarean Section Narcotic Requirements
This is planned as a multicenter project that will enroll 25 elective Cesarean section patients and gather demographic data, perioperative opioid requirements and perform genetic testing to seek preliminary evidence linking the extremes of opioid requirements (high and low) to genetics. This is intended as a pilot project to demonstrate proof of concept and the feasibility of a much larger multicenter study, with the eventual goal of defining the genomics of postoperative opioid requirements needed for pain control.
• 1
• 2
RPC01-3202: INDUCTION STUDY #2 - A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ORAL OZANIMOD AS INDUCTION THERAPY FOR MODERATELY TO SEVERELY ACTIVE CROHN S DISEASE
This is a Phase 3, randomized, double-blind, placebo-controlled study to determine the effect of oral ozanimod as an induction treatment for subjects with moderately to severely active CD, defined as a CDAI score ≥ 220 to ≤ 450. Approximately 600 subjects with active clinical symptoms and mucosal inflammation will be randomized in a 2:1 ratio to receive either ozanimod or placebo. Subjects will be stratified by prior biologic use and corticosteroid use at baseline. Approximately 50% of subjects with a history of treatment with marketed biologic agents (eg, TNF antagonists, anti-IL-12/23 and anti-integrin therapy) will be recruited. This limit will ensure the enrollment of subjects who have failed or been intolerant to corticosteroids or immunomodulators but never failed a TNF antagonist.
• Crohn's disease for ≥ 3 months on endoscopy and on histological exam
• Inadequate response or loss of response to corticosteroids, immunomodulators, and/or biologic therapy
• Crohn's Disease Activity Index (CDAI) score ≥ 220 and ≤ 450
• Average daily stool frequency ≥ 4 points and/or an abdominal pain of ≥ 2 points
• Simple Endoscopic Score for Crohn's Disease (SES-CD) score of ≥ 6 (or SES-CD ≥ 4 in participants with isolated ileal disease)
• Diagnosis of ulcerative colitis, indeterminate colitis, radiation colitis, or ischemic colitis, or has strictures with prestenotic dilatation requiring procedural intervention
• Extensive small bowel resection (>100cm) or known diagnosis of short bowel syndrome, or requires total parenteral nutrition
• Current stoma, ileal-anal pouch anastomosis, or fistula Other protocol-defined inclusion/exclusion criteria apply
The TrialNet Natural History Study of the Development of Type 1 Diabetes
• Individuals 2.5 to 45 years old who have an immediate family member with type 1 diabetes (such as a child, parent, or sibling)
• Individuals 2.5-20 years old who have an extended family member with type 1 diabetes (such as a cousin, niece, nephew, aunt, uncle, grandparent, or half-sibling)
• Individuals 2.5-45 years old without a type 1 diabetes proband, who are known to have 1 or more islet antibody are eligible for screening if needed to determine eligibility for a clinical trial to delay or prevent disease progression.
• Have diabetes already
• Have a previous history of being treated with insulin or oral diabetes medications.
• Currently be using systemic immunosuppressive agents (topical and inhaled agents are acceptable)
• Have any known serious diseases
Adaptive Phase II Study to Evaluate the Safety & Efficacy of NaBen®
• Male or female subjects who are between 12 and 17 years of age inclusive
• Physician confirmed DSM-IV or -V diagnosis of schizophrenia based on MINI International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders Studies for Children and Adolescents, version 6.0 (MINI-KID, Version 6.0)
• Are clinically stable with residual symptoms, defined as a total score of ≥ 60 of PANSS and a score of ≥ 40 for SANS
• An unchanged antipsychotic medication regimen for at least eight (8) weeks prior to randomization into the study and expected to remain unchanged during the study (longer for depot or long-acting antipsychotics: ten (10) months for Aripiprazole (Maintena®) and Paliperidone (Xeplion®); six (6) months for Olanzapine pamoate monohydrate (Zypadhera®); and at least 6 times duration of the reported half life or minimum four (4) months for other depot or long-acting antipsychotics)
• In good general physical health and all physical exam, neurological exam and laboratory assessments (urine/blood routine, biochemical tests and ECG) are clinically unremarkable per the investigator
• Subject has a negative urine illicit drug screening test
• Subject understands and is willing to sign the Informed Assent Form (IAF) prior to study entry and agrees to be available for all the study visits
• The subject's guardian understands and is willing to sign the Informed Consent Form (ICF) prior to study entry and agrees to be available for all the study visits
• Must not be a danger to self or others and must have family support available to be maintained as outpatients
• Meets the DSM-IV or -V criteria at screening for mental retardation, dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, or primary substance induced psychotic disorder. Other comorbid disorders; e.g., attention-deficit hyperactivity disorder (ADHD), are allowed as long as schizophrenia is the primary diagnosis and the comorbid disorder(s) do not require medication.
• Subjects whose illness was resistant to antipsychotics according to prior trials of two different antipsychotics of adequate dose
• History of epilepsy, head trauma, or neurological illness other than Tourette's syndrome
• History of allergic reaction to sodium benzoate
• Serious medical illnesses such as acute or chronic renal disease, liver failure or heart disease that, in the opinion of the investigator, may interfere with the conduct of the study.
• Current substance abuse or positive urine illicit drug screening or history of substance dependence (including alcohol, but excluding nicotine and caffeine) in the past three (3) months.
• Use of depot antipsychotics in the past six (6) months
• Inability to follow protocol
• Body Mass Index (BMI) > 35
• Female subjects who are pregnant (as confirmed by urine pregnancy test performed at screening Visit) or are nursing, or who do not agree to abstinence or birth control during the study
• Cancer within the last three (3) years except for basal cell carcinoma and squamous cell carcinoma
• Previous participation in an intervention trial within 30 days of randomization
• Subjects whose PANSS score has decreased more than 10 percent during the Screening Phase
Choline Supplementation as a Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorders Study
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.
• Ages 2 years to 5 years of age
• Available parent or legal guardian capable of giving informed consent for participation.
• Documented prenatal alcohol exposure (self-report, social service records, or adoption records).
• Modified Institute of Medicine (IOM) criteria for Fetal Alcohol Syndrome (FAS), Partial Fetal Alcohol Syndrome (PFAS), or Alcohol-Related Neurodevelopmental Disorder (ARND) (Hoyme, May, et al., 2005).
• Known history of a neurological condition (ex. epilepsy, traumatic brain injury)
• Known history of a medical condition known to affect brain function.
• Known history of other neurodevelopmental disorder (ex. autism, Down syndrome)
• Known history of very low birthweight (<1500 grams)
Maximizing the Impact of Neuroplasticity Using Transcranial Electrical Stimulation Study 1 (MINUTES)
• Ability to provide consent and comply with study procedures.
• Age 18 - 60 years old.
• Estimated IQ range within the range: 70 ≤ IQ ≤ 115.
• No Serious and Persistent Mental Illness (SPMI) or addictive disorder diagnosis as measured by the MINI (Mini International Neuropsychiatric Interview), or sleep disorder;
• Ability to participate in three weekly 45' training sessions over 12 weeks and participate in four assessments.
• Any medical condition or treatment with neurological sequelae (e.g. stroke, tumor, loss of consciousness > 30 min, HIV).
• Contraindications for tDCS or MRI scanning (tDCS contraindication: history of seizures; MRI contraindications: The research team will utilize the CMRR Center's screening tools and adhere to the screening SOP during enrollment of all research participants in this protocol. The CMRR Center's screening tools and SOP are IRB approved under the CMRR Center Grant (HSC# 1406M51205) and information regarding screening procedures is publicly available on the CMRR website (CMRR Policies / Procedures).
Study in Parkinson Disease of Exercise Phase 3 Clinical Trial: SPARX3 (SPARX3)
This study is a Phase 3 multi-site, randomized, evaluator-masked, study of endurance treadmill exercise on changes in the motor severity of Parkinson's disease after 12 months of exercise.
• A diagnosis of idiopathic Parkinson Disease based on the modified * United Kingdom (UK) PD brain bank criteria and which are consistent with recent criteria proposed for clinically established early established Parkinson's disease that no longer exclude individuals with a family history of Parkinson's disease.
• Hoehn and Yahr stages less than 3
• Disease duration: less than 3 years since disease diagnosis
• Age 40-80 years
• Positive DaTscan™ SPECT by quantitative readout for idiopathic Parkinson disease.
• Currently being treated with PD medications such as levodopa or dopamine receptor agonists, monoamine oxidase-B (MAO-B) inhibitors, amantadine, or anticholinergics.
• Expected to require treatment with medication for PD in the first 6 months of the study.
• Use of any PD medication 60 days prior to the baseline visit including but not limited to levodopa, direct dopamine agonists, amantadine, Rasagiline (Azilect), Selegiline (Eldepryl), Artane (trihexyphenidyl).
• Duration of previous use of medications for PD exceeds 60 days.
• Use of neuroleptics/dopamine receptor blockers for more than 30 days in the year prior to baseline visit, or any use within 30 days of baseline visit
• Presence of known cardiovascular, metabolic, or renal disease or individuals with major signs or symptoms suggestive of cardiovascular, metabolic, or renal disease without medical clearance to participate in the exercise program.
• Uncontrolled hypertension (resting blood pressure >150/90 mmHg)
• Individuals with orthostatic hypotension and standing systolic BP below 100 will be excluded. Orthostatic hypotension (OH) is a reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 3 minutes of standing.
• Hypo- or hyperthyroidism (TSH <0.5 or >5.0 mU/L), abnormal liver function (AST or ALT more than 2 times the upper limit of normal), abnormal renal function (creatinine clearance calculated by the Cockcroft-Gault equation <50mL/min, or estimated glomerular filtration rate using the MDRD4 equation or the CKD-EPI equation <45mL/min/1.73m2 ).
• Complete Blood Count (CBC) out of range and physician's judgment that abnormal value is clinically significant.
• Recent use of psychotropic medications (e.g., anxiolytics, hypnotics, benzodiazepines, antidepressants) where dosage has not been stable for 28 days prior to screening.
• Serious illness (requiring systemic treatment and/or hospitalization) within the last 4 weeks.
• Any other clinically significant medical condition, psychiatric condition, drug or alcohol abuse, assessment or laboratory abnormality that would, in the judgment of the investigator, interfere with the subject's ability to participate in the study.
• Montreal Cognitive Assessment (MoCA) score of <24.
• Beck Depression Inventory II (BDI) score > 28, indicating severe depression that precludes ability to exercise. Any subject with such a score will be referred to a PCP or physician for further evaluation and management of depression. Individuals with a BDI-II score of 17-28 will be excluded if any of the following conditions are met: (1) individual is suicidal, (2) is in need of depression treatment modification currently or (3) depressive symptoms likely to interfere with adherence to study protocol. Any subject with such a score will be referred to a PCP or physician for further evaluation and management of depression.
• Individuals who have been exercising at greater than moderate intensity for 120 minutes or more per week consistently over the last 6 months will be excluded. Greater than moderate intensity is defined as a range greater than 60-65% HRmax. These individuals are excluded since their exercise activities are greater than the activities they would experience if they were assigned to the 60-65% treatment group. As such, they would be expected to lose fitness.
• Use of the following within 90 days prior to the dopamine transporter (DAT) neuroimaging screening evaluation: bupropion, modafinil, armodafinil, metoclopramide, alpha-methyldopa, methylphenidate, reserpine, any amphetamine or amphetamine derivative. These can compromise DaTscan™ SPECT.
• Known allergy to iodinated products.
• Known hypersensitivity to DaTscan™ SPECT (either to the active substance of 123I-ioflupane or any of the excipients.
• (For women only) Actively breast-feeding an infant, and/or pregnant, or plan to become pregnant in the next 12 months.
• Other disorders, injuries, diseases, or conditions that might interfere with ability to perform endurance exercises (e.g. history of stroke, respiratory problems, traumatic brain injury, orthopedic injury, or neuromuscular disease).
A Study of JNJ-75229414 for Metastatic Castration-resistant Prostate Cancer Participants
The purpose of this study is to see if a new, investigational drug called JNJ-75229414 is safe and useful for treating patients with metastatic castration-resistant prostate cancer. JNJ-75229414 is a Chimeric Antigen Receptor T Cell (CAR-T) cell therapy.
• Histology: Metastatic CRPC (mCRPC) with histologic confirmation of adenocarcinoma. Metastatic CRPC with neuroendocrine features or mixed histology is excluded
• Prior Therapy: Prior treatment with at least 1 prior novel androgen receptor AR-targeted therapy (that is, abiraterone acetate, apalutamide, enzalutamide, darolutamide), or at least 1 prior chemotherapy (example, docetaxel)
• Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or detectable prostate-specific antigen (PSA) levels based on local laboratory results
• Fertile participants must use a condom with spermicide during any sexual contact with a woman of childbearing potential, including pregnant women, from the time of signing the ICF until 1 year after receiving a JNJ-75229414 infusion. Vasectomized participants must agree to use a condom to protect any sexual partner from exposure to semen for 1 year after receiving the last dose of study drug. Contraceptive (birth control) use should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies
• Prior Grade 4 Cytokine release syndrome (CRS) or Grade 3 or Grade 4 neurotoxicity related to any T cell redirection (Bispecific cluster of differentiation [CD 3])
• Prior Kallikrein 2 (KLK2)-targeted therapy
• Prior chimeric antigen receptor T cell (CAR-T) therapy
• Receiving systemic treatment less than or equal to (<=) 6 months prior to signing informed consent) for any invasive malignancy other than prostate cancer unless approved by the sponsor. Bisphosphonates initiated greater than or equal to (>=) 6 weeks prior signing informed consent are allowed
• Less than 2 weeks between last administration anti-androgen agents (example, abiraterone or enzalutamide) or radiotherapy, and less than 3 weeks between last administration of cytotoxic chemotherapy (example, docetaxel) or an investigational agent, and apheresis
Study Of Drinks With Artificial Sweeteners in People With Type 2 Diabetes (SODAS)
• Physician diagnosed type 2 diabetes ≥ 6 months prior to screening
• HbA1c 6.5-8.5% at participant screening
• Current treatment with lifestyle changes or stable diabetes-related medication levels for the past 3 months
• Willingness to provide consent to contact treating physician and physician agreement to refrain from changing diabetes-related medications during the trial (change defined as > 2 fold change in dose of any 1 hyperglycemic agent or addition or subtraction of an agent)
• No physician-directed medication change for 3 months if prescribed medication for lipids or blood pressure
• Usual consumers of diet beverages (≥ 3 servings/ week (24 oz.) and the willingness to maintain fidelity of the intervention, and participate in all aspects of the intervention
• Not actively looking to make major lifestyle alterations during the study period with stable weight for 2 months (within 3%).
• Type 1 diabetes or suspected type 1 diabetes (lean with polyuria, polydipsia, and weight loss with little response to metformin)
• "Secondary" diabetes due to specific causes (e.g. monogenic syndromes, pancreatic surgery, and pancreatitis)
• Diabetic Ketoacidosis hospitalization within last 6 months
• Severe/major hypoglycemia in the last 3 months-severe/major hypoglycemia is defined as a hypoglycemic event in which patient requires assistance of another person to manage the episode
• Glucocorticoid use (prednisone 2.5 mg/d or more or its equivalent)
• History of intolerance or allergy to diet beverages or AS or phenylketonuria
• Any condition that is known to affect the validity of the glycemic measures (Hba1c)
• Major cardiovascular disease event or surgery within past 6 months
• Gastrointestinal disease
• Renal or liver disease
• Current treatment for cancer
• Those with major surgery planned or history of bariatric surgery
• Antibiotic treatment (> 6 days) within past 6 months
• Currently pregnant (via self-report) or planning to become pregnant during study period; <1 year postpartum and breast feeding
• Current participation in another interventional clinical trial
• Previous randomization in this study,
• Heavy alcohol consumption (on average >2 drinks/day for women and >3 drinks/day for men)
• Habitual consumer of SSB ≥ 1 serving / day (8 oz.)
• Does not drink diet beverages
• BMI < 20.0 kg/m2
MT2020-33: Study of FT538 in Combination with Daratumumab in Acute Myeloid Leukemia
This study is designed to find the maximum tolerated dose (MTD) of FT538 when given in combination with daratumumab for the treatment of acute myeloid leukemia (AML).
• CD38 expression is defined by ≥20% of malignant cells with CD38 expression by flow cytometry on the most recent marrow biopsy (within 30 days of enrollment - archived or fresh).
• Relapsed/refractory is defined as failure to achieve at least a Morphological Leukemia Free State (MLFS) or reverting from MLFS.
• Lines of therapy are defined as (must have had 2 prior therapies):
• One cycle of Intensive induction chemotherapy such as 7+3, 5+2, MEC, FLAG, FLAG-Ida, CLAG ± small molecule inhibitor
• Four weeks of HMA-based induction ± small molecule inhibitor
• Hematopoietic stem cell transplantation (HSCT) if relapse that occurs > 90 days after HSCT
• Gemtuzumab Ozogamicin
• LDAC + glasdegib
• Biomarker-specific targeted agents (FLT3 inhibitors, IDH1/2 inhibitors, others if available)
• Other treatments could be considered after discussion with the PI
• Age 12 years or older at the time of consent - Please note, enrollment of minors will be begin until permission to proceed is received from the FDA. At that time, the protocol will be updated to open enrollment to minors.
• Weight ≥ 50 kg due to FT538 fixed cell dosing and FT538 product pre-dose packaging
• Karnofsky performance status of 80-100% for 16 years and older or Lansky Play Score of 80-100 for ≥12 and < 16 years of age
• Evidence of adequate organ function within 14 days of starting study treatment defined as:
• Estimated Glomerular Filtration Rate (estimated creatinine clearance) ≥50 mL/min/1.73m^2
• Total bilirubin ≤ 5 × upper limit normal (ULN), not applicable for patients with Gilbert's syndrome
• AST ≤3 × ULN and ALT ≤ 3 × ULN, not applicable if determined to be directly due to underlying malignancy
• LVEF ≥ 40% by echocardiogram or MUGA
• Contraceptive use by men or women
• Female subjects: Women of childbearing potential (WOCBP) must use a highly effective form of contraception from the screening visit until at least 12 months after the final dose of cyclophosphamide (CY), at least 4 months after the final dose of FT538, and at least 3 months after the final dose of daratumumab, whichever is latest.
• Male subjects: Males with a female partner of childbearing potential or a pregnant female partner must be sterile (biologically or surgically) or use a highly effective method of contraception from the screening visit until at least 4 months after the final dose of CY and at least 4 months after the final dose of FT538, and at least 3 months after the final dose of daratumumab, whichever is latest.
• Must agree to and sign the consent for the companion Long-Term Follow-Up study (UMN CPRC #2020LS166) to fulfill the FDA required 15 years of follow-up for a genetically modified cell product.
• Must agree to and sign the consent for the companion Long-Term Follow-Up study (UMN CPRC #2020LS166) to fulfill the FDA required 15 years of follow-up for a genetically modified cell product.
• Diagnosis of acute promyelocytic leukemia (APL)
• Pregnant or breastfeeding, Menstruating females of child-bearing potential must have a negative pregnancy test within 14 days of study treatment start
• Known allergy to any of study drugs or their components
• Clinically significant cardiovascular disease including any of the following: myocardial infarction within 6 months prior to first study treatment; unstable angina or congestive heart failure of New York Heart Association Grade 2 or higher or cardiac ejection fraction <40%
• Any known condition that requires systemic immunosuppressive therapy (> 5mg prednisone daily or equivalent) during the FT538 dosing period (3 days before the 1st dose through 14 days after the last dose) excluding pre-medications - inhaled and topical steroids are permitted
• Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to Day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to the to the first dose of daratumumab. Maintenance hydroxyurea for blast control up to the initiation of lympho-conditioning is permitted
• Known active central nervous system (CNS) involvement or treated CNS disease that has not cleared. If prior disease related CNS involvement must have completed effective treatment of their CNS disease at least 2 months prior to Day 1 with no evidence of disease clinically and at least stable findings on relevant CNS imaging
• Non-malignant CNS disease such as epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
• Clinically significant untreated/uncontrolled infection
• Live vaccine <6 weeks prior to start of lympho-conditioning
• Known seropositive for HIV or known active Hepatitis B or C infection with detectable viral load by PCR
• Prior solid organ transplant
• Allogeneic HSCT relapse occurring <90 days after HSCT
• Active graft-versus-host-disease (GvHD) requiring systemic immunosuppression within 14 days prior to enrollment
• Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to the participant.
Clinical Trial of Two Study Drinks in Detoxification of Environmental Toxicants and Carcinogens
The goal of this proposal is to test the hypothesis that consumption of watercress, a rich source of the cancer chemopreventive agent 2-phenethyl isothiocyanate (PEITC), will enhance the detoxification of multiple environmental toxicants and carcinogens, particularly in subjects who are null for glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), or both. If our hypothesis is supported by the results of the trial, watercress could emerge as an inexpensive and plentiful dietary constituent which could promote good health by decreasing the effects of environmental stressors.
• Adult Male or female. Participants can be smokers or non-smokers
• In good physical health
• In stable and good mental health
• Not using any medications that may affect the Nrf2 pathway
• Women who are not pregnant or nursing or planning to become pregnant
• Participants have provided written informed consent to participate in the study
• Significant immune system disorders, respiratory diseases, kidney or liver diseases or any other medical disorders that may affect biomarker data as determined by the licensed medical professional
• Vital signs outside of the allotted range
• Not willing to abstain from eating cruciferous vegetables during the course of the study
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.
Clinical Study of Cannabidiol in Children and Adolescents With Fragile X Syndrome (RECONNECT)
This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the efficacy and safety of CBD administered as ZYN002, a transdermal gel, for the treatment of children and adolescent patients with FXS. Qualified male and female patients with FXS will enter a two-week single-blind placebo lead-in period. Following the placebo lead-in, patients meeting randomization criteria will receive double-blind treatment for 16 weeks. The study will be comprised of a Screening visit and a combination of seven onsite (face-to-face) and virtual study visits. Approximately 204 male and female patients, ages 3 to < 18 years, will be randomized 1:1 to either trial drug or placebo. Randomization will be stratified by gender (male, female), methylation status (complete, partial), and by weight (≤50 kg, >50 kg).
• Male or female children and adolescents aged 3 to < 18 years, at the time of Screening.
• Judged by the Investigator to be in generally good health at Screening based upon the results of medical history, physical exam, 12-lead ECG and clinical laboratory test results. -Laboratory results outside the reference range must be documented as not clinically significant by both the Investigator and Sponsor.
• Participants must have a diagnosis of FXS through molecular documentation of full mutation of the FMR1 gene documented through genetic testing at Screening.
• Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of no more than two anti-seizure medications (ASMs) for the four weeks preceding study Screening; or must be seizure-free for one year if not currently receiving ASMs.
• Patients taking psychoactive medication(s) should be on a stable regimen of not more than three such medications for at least fours weeks preceding Screening and must maintain that regimen throughout the study. Psychoactive medications include (but are not limited to) antipsychotics, antidepressants, anxiolytics, attention-deficit / hyperactivity disorder (ADHD) medications, and medications for sleep.
• If patients are receiving non-pharmacological, behavioral and/or dietary interventions, they must be stable and have been doing so for three months prior to screening.
• Patients have a body mass index between 12-30 kg/m2 (inclusive).
• Females of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative serum or urine pregnancy test at all designated visits.
• Patients and parents/caregivers must be adequately informed of the nature and risks of the study and given written informed consent prior to Screening.
• Patients and parents/caregivers agree to abide by all study restrictions and comply with all study procedures, and in the Investigator's opinion, are reliable and willing and able to comply with all protocol requirements and procedures.
• Females who are pregnant, nursing or planning a pregnancy; females of childbearing potential and male patients with a partner of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined below for the duration of therapy and for three months after the last dose of study medication. Standard acceptable methods of contraception include abstinence (defined as refraining from heterosexual intercourse from screening to three months after the last dose of study medication) or the use of a highly effective method of contraception, including hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide, vasectomy, or intrauterine device. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception.
• History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients.
• Exposure to any investigational drug or device less than or equal to 30 days prior to Screening or at any time during the study.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin levels greater than or equal to 2 times the upper limit of normal or alkaline phosphatase levels greater than or equal to 3 times the upper limit of normal.
• Use of cannabis or any THC or CBD-containing product within 3 months of Screening Visit or during the study (aside from ZYN002).
• Patient has a positive drug screen, including ethanol, cocaine, THC, barbiturates, amphetamines (unless prescribed), benzodiazepines (except midazolam or comparable administered for blood draws and ECG collection), and opiates.
• Patient is using the following AEDs (medications for the treatment of seizures and/ or epilepsy): clobazam, phenobarbital, ethosuximide, felbamate, carbamazepine, phenytoin, or vigabatrin.
• Patient is using a strong inhibitor/inducer of CYP3A4 or sensitive substrate of CYP3A4 including but not limited to the following medications: midazolam (except single doses administered for the purposes of obtaining blood samples and ECG's), oral ketoconazole, fluconazole, nefazadone, rifampin, alfentanil, alfuzosin, amiodarone, cyclosporine, dasatinib, docetaxol, eplerenone, ergotamine, everolimus, fentanyl, halofantrine, irinotecan, lapatinib, levomethadyl, lumefantrine, nilotinib, pimozide, quinidine, ranolazine, sirolimus, tacrolimus, temsirolimus, toremifene, tretinioin, vincristine, vinorelbine, St. John's Wort, and grapefruit Juice/products.
• Patients may not be taking any benzodiazepines (except single doses administered for the purposes of obtaining blood samples and ECGs) at screening or throughout the study.
• Patient is expected to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
• Patient has an advanced, severe, or unstable disease that may interfere with the study outcome evaluations.
• Patient has acute or progressive neurological disease, psychosis, schizophrenia or any other psychiatric disorder or severe mental abnormalities (other than FXS) that are likely to require changes in drug therapy or interfere with the study objectives or ability to adhere to protocol requirements.
• Patient has a positive result for the presence of HBsAg, HCV, or HIV antibodies.
• Patient has known history of cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, exercise-related cardiac events including syncope and pre-syncope, risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or other serious cardiac problems.
• Any clinically significant condition or abnormal findings at the Screening Visit that would, in the opinion of the Investigator, preclude study participation or interfere with the evaluation of the study medication.
• Any skin disease or condition including eczema, psoriasis, melanoma, acne, contact dermatitis, scarring, imperfections, lesions, tattoos, or discoloration that may affect treatment application, application site assessments or absorption of the trial drug.
• History of treatment for, or evidence of, drug abuse within the past year.
• Previous participation in a ZYN002 study (with the exception of patients who were screen failures in Study ZYN2-CL-016 and did not enter Study ZYN2-CL-017).
• Patient responds "yes" to Question 4 or 5 on the C-SSRS (Children) during Screening or at any time on 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.
Intravenous Subanesthetic Repeated Dose of Ketamine in Treatment Resistant Depression: A Pilot Study
The overall objective of this proposal is to determine the efficacy of a single vs. multiple sub-anesthetic IV ketamine infusions for patients with TRD. We plan to conduct a randomized controlled trial (RCT) comparing a single ketamine infusion preceded by 5 midazolam infusions vs. six ketamine infusions.
Choline Supplementation as a Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorders Study (CHOLINE4)
• 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.
• 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)
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.
Early Intervention for Very Low Birth Weight Infants: Equity and Neurodevelopment (EVEN Study)
This study uses parental surveys and standard neurodevelopment testing to better understand the experience of families of very low birth weight infants with early intervention services in Minnesota. We are particularly interested in understanding how inequity, bias, and discrimination contribute to disparities in neurodevelopment outcomes for this population.
Study of Ociperlimab (BGB-A1217) in Combination With Tislelizumab in Advanced Solid Tumors
This is an open-label, multicenter, Phase 1 and Phase 1b study to evaluate the safety and preliminary antitumor activity of BGB-A1217 in combination with tislelizumab in patients with unresectable locally advanced or metastatic solid tumors. The primary endpoint of the Phase 1b portion includes: •Overall response rate (ORR), as determined by investigator derived tumor assessments per RECIST v1.1 for each tumor expansion cohort.
• Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
• ≥ 1 measurable lesion per RECIST v1.1.
• Has adequate organ function.
• phase 1- Patients with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors who have previously received standard systemic therapy or for which treatment is not available, not tolerated or refused. Phase 1b Key Inclusion Criteria
• Signed informed consent form (ICF) and able to comply with study requirements.
• Age ≥ 18 years (or the legal age of consent) at the time the ICF is signed.
• Histologically or cytologically confirmed tumor types in the following disease cohorts: Cohort 1: stage IV squamous NSCLC Cohort 2: stage IV non-squamous NSCLC Cohort 3: stage IV squamous or non-squamous NSCLC with PD-L1 positive. Cohort 4: extensive-stage SCLC Cohort 5: stage IIIB, IIIC or IV NSCLC Cohort 6: stage IV ESCC Cohort 7: stage IV EAC Cohort 8: recurrent or metastatic HNSCC incurable by local therapies Cohort 9: stage IV G/GEJ adenocarcinoma. Cohort 10: stage IV squamous or non-squamous NSCLC with PD-L1 positive.
• ECOG Performance Status ≤ 1
• Adequate organ function
• Willing to use highly effective method of birth control Phase 1 Key
• Active brain or leptomeningeal metastasis.
• Active autoimmune diseases or history of autoimmune diseases that may relapse.
• With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for patients with hepatocellular carcinoma).
• Concurrent participation in another therapeutic clinical trial.
• Received prior therapies targeting TIGIT. Phase 1b Key
• Patients with any prior therapy for recurrent/metastatic disease.
• Non-squamous NSCLC patients with sensitizing epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion, and c-ros oncogene 1 (ROS1) fusion.
• Gastric cancer patients with squamous or with positive HER2 expression.
• Prior therapy with any drug specifically targeting T-cell co-stimulation or checkpoint pathways. (anti-PD(L)1 exception for Cohort 5).
• Active leptomeningeal disease or uncontrolled brain metastasis.
• Active autoimmune diseases or history of autoimmune diseases that may relapse.
• With severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection, etc. (antiviral therapy is permitted for patients with hepatocellular carcinoma).
• Concurrent participation in another therapeutic clinical study. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
The MOMENTUM Study (Monitoring Maternal Emergency Navigation and Triage on Mfangano): A 12-month community-based cohort study to evaluate delays in access to maternal and newborn emergency care in Western Kenya (MOMENTUM)
This study is a 12-month socio-behavioral observational cohort study assessing delays, barriers, and current standard of care among women and newborns seeking access to emergency pregnancy, obstetrical and neonatal care among at health facilities on Mfangano Island, Lake Victoria Kenya.
• Must be ≥18 years of age as of the date of study eligibility, or qualify as an emancipated minor (ie: person aged less than 18 years who was married, pregnant, or a parent, consistent with Government of Kenya guidelines and previous research such as Kenya AIDS Indicator Survey-KAIS)
• Must be conversant with one of the commonly spoken languages within the study area (i.e. DhoLuo, Swahili or English; prior experience indicates that this represents >99% of the adult population)
• Must be willing to share confidential information about prenatal history, pregnancy course, obstetrical complications, clinical course, and experiences navigating health care system.
• Must have the ability to provide informed consent. Emergency Cohort-Specific Criteria:
• Participants will be either patients who have experienced a critical pregnancy-related, obstetric, or neonatal health emergency, or appropriate family member in the case that patient is not able to participate in interview due to death or illness or other circumstance. Birth Planning Cohort-Specific Criteria:
• All pregnant women who register a birth plan through the Health Navigation Birth Planning service will be eligible to enroll in the Birth Planning Cohort Focus Group Cohort-Specific Criteria:
• All participants from the emergency cohort and the birth planning cohort will be eligible, as well as CHW volunteers, and OHR-EKC and MoH health facility staff
• Individuals under the age of 18 and who do not qualify as emancipated minors
• Individuals who do not speak either English, Dholuo or Swahili
• Individuals who are not comfortable sharing confidential information about prenatal history, pregnancy course, obstetrical complications, clinical course, and experiences navigating health care system.
Clinical Study of the ARTISAN Aphakia Lens for the Correction of Aphakia in Children
In this study, subjects who had a cataract removed but due to their eye structure, are not able to have a traditional intraocular lens (IOL) implanted, receive a special type of lens called the ARTISAN IOL. The objective of this study is to determine the effectiveness of the ARTISAN IOL and to precisely define the associated risks and, if possible, identify particular groups of patients who may be at high risk of developing complications resulting from the surgical procedure of implanting the lens.
• 2 to 21 years of age
• Have a visually significant cataract or need IOL replacement surgery
• Compromised capsular bag prohibiting implantation of standard posterior IOL
• Subject or parent/guardian must be able to comply with visit schedule and study requirements
• Subject's legal representative must be able to sign the Informed Consent
• Under 2 years of age
• Unable to meet Postoperative evaluation requirements
• No useful vision or vision potential in fellow eye
• Mentally retarded patients
• History of corneal disease
• Abnormality of the iris or ocular structure
• ACD less than 3.2 mm
• Uncontrolled glaucoma
• IOP > 25 mmHg
• Chronic or recurrent uveitis
• Preexisting macular pathology that may complicate the ability to assess the benefit of this lens
• Retinal detachment or family history
• Retinal disease that may limit visual potential
• Optic nerve disease that may limit visual potential
• Diabetes mellitus
• Pregnant, lactating or plan to become pregnant
Clinical Study of the BioVentrix Revivent TC System for Treatment of Left Ventricular Aneurysms
The purpose of the study is to demonstrate the safety and effectiveness of the BioVentrix Revivent TC System for the treatment of LV antero-septal aneurysms/scars in patients with symptomatic heart failure. This study is prospective, multi-center, dual-arm with 2:1 study vs. control pool allocation ratio, pivotal study designed to evaluate the safety and effectiveness of the BioVentrix Revivent TC System for treatment of Left Ventricular (LV) Antero-Septal Aneurysms/Scars in Patients with Symptomatic Heart Failure. Patients will be selected for enrollment by a Heart Team at each clinical site that will be minimally composed of a heart failure specialist, an Interventional cardiologist, and a cardiac surgeon, one of whom is the site PI. The Heart Team will guide patient selection by pre-procedural agreement of the entire heart team regarding anatomic suitability and eligibility prior to selection of the patient by the Study PI. The Heart Team will optimize procedural performance (joint Interventionalist and cardiac surgical participation), and provide optimal and equivalent Guideline Directed Medical Therapy for residual or ongoing heart failure symptoms in test (post-procedural) and control group patients as determined by the heart failure specialist and referring physician
• 18 years old or older
• LV Aneurysm or Scar Presence: Defined by presence of a contiguous acontractile (akinetic and/or dyskinetic) scar;
• LV Aneurysm/Scar Location: Defined as a scar involving septum and/or anterior, apical or anterolateral regions of the left ventricle as evidenced by cardiac imaging and referred for surgical management;
• Viability of myocardium in regions remote from area of intended scar exclusion as evidenced by cardiac imaging;
• Left Ventricular Ejection Fraction < 45%;
• Left ventricular end-systolic volume index ≥50 mL/m2;
• Suffering from heart failure symptoms as defined by NYHA Classification > 2 not responsive to medical therapy;
• Patient completed 6 Minute Walk Test and MLHF Quality of Life Questionnaire (can be performed at baseline visit);
• Patient is on adequate Guideline Directed Medical Therapy (GDMT);
• Subject or a legally authorized representative must provide written informed consent;
• Agree to required follow-up visits; and
• Female subject of childbearing potential does not plan pregnancy for at least one year following the index procedure. For a female of childbearing potential, a pregnancy test must be performed with negative results known within seven days prior to index procedure Candidates for the study group must meet ALL of the inclusion criteria. Candidates allocated to active concurrent control pool of patients must meet all inclusion criteria (including LV Aneurysm/Scar Presence), WITH THE EXCEPTION OF ONE OF THE FOLLOWING:
• They have undergone previous pericardiotomy, left thoracotomy, or open heart surgery, or
• The LV Aneurysm/Scar location does not permit treatment with the study device, or
• The patient elects to be enrolled in the control group
• Cardiac Resynchronization Therapy (CRT) or ICD pacing lead placement ≤ 60 days prior to enrollment;
• Valvular heart disease, which in the opinion of the investigator, will require surgery;
• Functional Mitral Regurgitation greater than moderate (i.e. EROA>20mm sq.) and degenerative MR (including MR due to papillary muscle rupture);
• Need for coronary revascularization, in the opinion of the site investigator;
• Peak Systolic Pulmonary Arterial Pressure > 60 mm Hg via echo or right heart catheterization and/or evidence of cor pulmonale;
• Myocardial Infarction within 90 days prior to enrollment;
• Within the last six months, a prior CVA or TIA, or any intracranial hemorrhage, or any permanent neurologic deficit, or any known intracranial pathology;
• Co-morbid disease process with life expectancy of less than one year or active malignancy not in remission;
• Any solid organ transplant or is on waiting list for any solid organ transplant other than cardiac;
• Chronic renal failure with a serum creatinine >2.5 mg/dL and/or GFR<30ml/min;
• Subject is currently participating in another clinical trial that has not yet completed its primary endpoint;
• Presence of significant ventricular arrhythmias The following exclusion criteria apply only to the treatment group and do not apply to the concurrent control cohort:
• Contraindication or inability to adhere to systemic anticoagulation;
• Known hypersensitivity or contraindication to device materials;
• Previous pericardiotomy or left thoracotomy;
• Pathology/previous surgery/radiation therapy of the right neck that would interfere with placement of a 14F delivery catheter;
• Prior open heart surgery or significant pericarditis;
• Calcified ventricular wall in the area of intended anchor implants as verified by cardiac imaging;
• Thrombus or intra-ventricular mass in the left atrium or ventricle as verified by cardiac imaging that has not been adequately treated with anticoagulant.
• Functioning pacemaker leads in antero-apical RV, which, in the opinion of the investigator, would interfere with anchor placement;
An Open Label Study to Evaluate DPCP Ointment for the Treatment of Alopecia Areata
This is an open labeled study to determine the response and characteristics, safety and efficacy, of the proprietary DPCP ointment composition as a topical immunotherapeutic agent for the treatment of extensive alopecia areata.
• Subject has clinical diagnosis of extensive alopecia areata (76%-99% involvement as determined by SALT score, Appendix B, Part I).
• Written informed consent and HIPAA authorization have been obtained.
• Subject is > 18 to years of age.
• Female subjects of childbearing potential have a negative pregnancy test and agree to use an acceptable, highly effective method of birth control (i.e., failure rate of less than 1% per year) to prevent pregnancy.
• Subject agrees to comply with protocol requirements and attend all required study visits and is considered to be a good study subject.
• Subject meets concomitant medication washout requirements -
• Subject has <76 or greater than 99% hair loss.
• Subject is pregnant or lactating.
• Subject has current controlled or uncontrolled bacterial, viral (with the exception of herpes simplex), fungal, atypical, or opportunistic infection(s).
• Subject has a history of substance abuse within the past five years.
• Immunosuppression (history of transplantation, chemotherapy, splenectomy, HIV).
• Administration of systemic treatment (e.g., Imuran, biologics) that have an immunomodulatory mechanism of action in the preceding 3 months.
• Previous treatment with DPCP.
• Application of topical immunomodulating agent in the preceding 6 weeks.
• Application of topical or intralesional corticosteroids within the past 6 weeks.
• Systemic (oral, inhaled, or intravenous) administration of corticosteroid or other systemic treatment (i.e., prednisone) with an immunosuppressive mechanism of action within the past 3 months.
• Use of light treatments (e.g., PUVA, narrow band UVB) in the preceding 6 weeks.
• Use of Anthralin in preceding 6 weeks.
• Use of minoxidil, topical or oral, in the preceding 4 weeks.
• Subject is currently or has undergone systemic therapy for malignancy within the past five years except for adequately treated Squamous Cell Carcinoma (SCC) or Basal Cell Carcinoma (BCC) of the skin.
• Clinical evidence of secondary skin infection (i.e., folliculitis).
• Participation in other therapeutic investigational clinical trials within 4 weeks of enrollment.
• Evidence of anemia, thyroid disease, sarcoidosis or other medical condition that could be adversely affected by participating in the study.
• Subject has any medical condition that, in the judgment of the Investigator, would jeopardize the subject's safety following exposure to the administered medications. -
A Phase 3 Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer
The current proposal, a randomized phase 3 study, will be the first to investigate the potential of combined potent androgen signaling blockade to lead to durable relapse-free survival in the castration-sensitive setting. Positive results from the current study would justify the implementation of potent androgen signaling inhibition in high-risk biochemically recurrent prostate cancer. Comparisons between three randomized arms, in a 1:1:1 fashion, is proposed as the design to test the efficacy of portent androgen signaling blockade. The arms of the study are (1) Control arm consisting of degarelix monotherapy, (2) Experimental arm consisting of apalutamide in combination with degarelix, and (3) Experimental arm consisting of apalutamide, abiraterone acetate + prednisone, and degarelix.
• Histologically confirmed prostate adenocarcinoma
• Prior radical prostatectomy
• Biochemically recurrent prostate cancer with PSA doubling time ≤ 9 months at the time of study entry. Calculation of PSA doubling time should include the use of all available PSA values obtained within past 6-12 months prior to randomization, with a minimum of 3 values separated by at least 2 weeks apart. PSA values obtained prior to therapeutic interventions (e.g. salvage radiation) will be excluded. PSA doubling time to be estimated using Memorial Sloan Kettering Cancer Center online calculator (https://www.mskcc.org/nomograms/prostate/psa-doubling-time)
• Prior adjuvant or salvage radiation or not a candidate for radiation based upon clinical assessment of disease characteristics and patient co-morbidities.
• Screening PSA > 0.5 ng/mL
• No definitive evidence of metastases on screening CT or MRI of abdomen/pelvis and radionuclide whole body bone scan per the judgment of the investigator. Abdominal and/or pelvic lymph nodes measuring 2 cm or less in short axis diameter are allowed. Lesions identified on other imaging modalities (e.g. PSMA or choline PET) that are not visualized on CT and/or MRI or radionuclide bone scan are allowed. Equivocal lesions on bone scan should be followed up with additional imaging as clinically indicated.
• Screening serum testosterone > 150 ng/dL
• Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0 or 1
• Age ≥ 18 years
• Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to cycle 1 day 1
• Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.
• Adequate organ function as defined by the following laboratory values at screening:
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) < 2.5 x upper limit of normal (ULN)
• Total serum bilirubin ≤1.5 x ULN. In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
• Serum potassium ≥ 3.5 mmol/L. Supplementation and re-screening is allowed.
• Estimated creatinine clearance > 45 ml/min using Cockroft-Gault equation
• Platelets ≥ 100,000/microliter independent of transfusion and/or growth factors within 3 months prior to randomization
• Hemoglobin ≥ 9.0 g/dL independent of transfusion and/or growth factors within 3 months prior to randomization
• Serum albumin ≥ 3.0 g/dL
• Prior androgen deprivation therapy and/or first generation anti-androgen (e.g. bicalutamide, nilutamide, flutamide) for biochemically recurrent prostate cancer. Prior ADT and/or first generation anti-androgen in the (neo)adjuvant and/or salvage setting before, during, and/or following radiation or surgery is allowed provided last effective dose of ADT and/or first-generation anti-androgen is > 9 months prior to date of randomization and total duration of prior therapy is ≤ 36 months.
• Prior treatment with CYP17 inhibitor (e.g. ketoconazole, abiraterone acetate, galeterone) or second generation androgen receptor antagonist including apalutamide or enzalutamide
• Prior chemotherapy for prostate cancer except if administered in neoadjuvant or adjuvant setting
• Use of 5-alpha reductase inhibitor within 42 days prior to cycle 1 day 1
• Use of investigational agent within 28 days prior to randomization
• Use of other prohibited medications within 7 days prior to cycle 1 day 1 on study (Arms B and C only)
• Prior bilateral orchiectomy
• Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
• Uncontrolled hypertension
• Gastrointestinal disorder affecting absorption or the ability to swallow tablets
• Baseline severe hepatic impairment (Child-Pugh Class B & C)
• Intercurrent illness that is not controlled such as active infection, psychiatric illness/social situations that would limit compliance with study requirements
• Any chronic medical condition requiring a higher dose of corticosteroid than equivalent of 5 mg prednisone/prednisolone once daily
Longitudinal study of bone and endocrine disease in children with MPS I, II, and VI
This multi-centered, longitudinal study of male and female participants with MPS I, II, and VI has an overall objective to document the progression of skeletal disease and identify biomarkers through the use of bone imaging, range of motion tests, and biomarker analysis that either predict disease severity or could be used as therapeutic targets.
• Diagnosis of MPS I, II, or VI
• Ability to travel to study center for evaluations.
• Age ≥ 5 years and < 35 years: age at entry into study must be ≥5 years and ≤33 years to ensure a minimum of 2 study visits.
• Pregnancy (will be determined at each study visit)
• Participation in any other study within the past 12 months which would result in increasing the child's radiation exposure above 500 mrem for the calendar year.
• Participants who cannot comply with study procedures or have other factors that would inhibit their participation as determined by the PI's discretion.
An Open-Label, Safety Study for Previously Treated Ataluren (PTC124) Patients with Nonsense Mutation Dystrophinopathy
a Phase 3, open-label, safety study of ataluren in patients who previously received ataluren at an investigational site in a prior PTC-sponsored clinical study or treatment plan.
• Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible Institutional Review Board/Independent Ethic Committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the participant should be followed.
• History of exposure to ataluren in a prior PTC study or treatment plan and effected nmDBMD siblings of those participants (provided those participants have completed the placebo-controlled portion of the trial).
• Fertile men, who are sexually active with women of childbearing potential and who have not had a vasectomy, must agree to use a barrier method of birth control during the study and for up to 50 days after the last dose of study drug.
• Willingness and ability to comply with scheduled visits, drug administration and return plan, study procedures, laboratory tests, and study restrictions Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation should be considered.
• Exposure to another investigational drug within 1 month prior to start of study treatment.
• Eligibility for another ataluren clinical trial that is actively enrolling study participants.
• Positive for Hepatitis B core antibody or Hepatitis C antibody at screening for ataluren naïve participants (siblings) or participants who have a temporary treatment gap of 1 year before entering study.
• Known hypersensitivity to any of the ingredients or excipients of ataluren (refined polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, colloidal silica, magnesium stearate).
• Ongoing intravenous (IV) aminoglycoside or IV vancomycin therapy.
• Ongoing uncontrolled medical/surgical condition, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant or make it unlikely that follow-up would be completed.
Determinants of Renal Structural Responses to Enzyme Replacement Therapy (ERT) in Fabry Disease Study (LDN6702)
The effect of enzyme replacement therapy on how well your kidneys are responding to enzyme replacement therapy (ERT) is not clear from blood and urine tests alone, but may be more clear in comparisons of kidney biopsies performed before and some time after ERT has been initiated, and this is what we are focusing our study efforts on. The purpose of this study is to obtain your permission to allow us to study the kidney biopsy tissues (collected for medical reasons) after the regular routine studies have been completed. Through our special research measurements and additional study, we hope to be able to see and measure very specific changes in the kidney tissues from Fabry patients taking ERT. We also hope that through these studies of what happens within the kidney before and after starting ERT, we are able to reveal valuable information about the importance of factors like your age that you started ERT, the amount or dosage of ERT, and any differences seen between males and females.
• Patients diagnosed with Fabry disease who have/have not received enzyme replacement therapy where a clinical decision has been made to obtain a kidney biopsy, a GFR, and urinary albumin studies or where patients have previously completed clinical trials which included measures of renal function and renal biopsies.
• Patients with serum creatinine more than 2.5 mg/dL or known to have a renal disease other than Fabry.