Clinical Trials

SMA treatments will be reviewed to see what effect they have on your child as follows:–To assess the effectiveness of treatments for SMA

–To assess long-term safety
–To assess overall survival of all subjects with SMA
–To assess healthcare utilization
–To assess caregiver burden
–To assess participant functional independence

Information about your child’s SMA treatment will be collected for the registry for a period of up to 15 years.

• Male or female, at least 18 years of age (inclusive).
• Diagnosis of ALS made by a physician experienced with the management of ALS.
• >36 months from symptom onset defined as first weakness.
• Capable of providing informed consent.
• Capable of and willing to follow program procedures.
• Participants who have established care with a physician experienced in treating patients with ALS involved in the program and will maintain this clinical care throughout the duration of their time in the program.
• Women of childbearing potential (e.g., not post-menopausal for at least one year or surgically sterile) must agree to use adequate birth control for the duration of the program and 3 months after last dose of AMX0035; women must not be planning to become pregnant for the duration of the program and 3 months after last dose of study drug
• Men must agree to practice contraception for the duration of the program and for at least 3 months after last dose of program drug; men must not plan to father a child or provide sperm for donation for the duration of the program and 3 months after last dose of study drug.

Participating sites enroll neonates or children who have had an ischemic stroke or are at high risk of having a stroke into the registry. Participants have their medical and research records reviewed for information about their stroke and abstracted into a secure electronic database called REDCap. The IPSS also provides an attractive imaging platform (through the Stroke Imaging Lab for Children, SILC, housed at SickKids) for sites to share clinically acquired brain images that will complement the clinical dataset. The clinical and imaging datasets will improve our understanding of the processes underlying plasticity and recovery in childhood stroke.

All information captured in the study is de-identified.

This study does not require any interventions or additional visits for research. Two outcome measures are typically administered during a follow-up clinic visit: the Paediatric Stroke Outcome Measure (PSOM) and the Recovery and Recurrence Questionnaire (RRQ). The PSOM is used during clinic visits by the study PI or co-investigator; the RRQ is a parental questionnaire that can be completed during clinic visits or by telephone interview for those parents who cannot attend the follow up appointment. Both measures assess neurological function in the following 5 domains: sensory, motor, language, cognition and behavior.

Participating investigators will retain ownership of their own (single-site) data. However, by entering data into the IPSS, co-investigators give implicit permission for the IPSS to analyze the collective dataset. These contributing investigators are recognized through authorship.

Subjects will visit the clinic for a screening visit, regular assessments and to receive the study drug for 44 weeks.

Subjects will provide blood to measure standard safety labs and K0706 levels. If subjects consent, additional blood will be collected, processed, and frozen for future analyses of emerging tests related to PD progression and K0706 target engagement (e.g., proteins, genetic markers). Subjects may also be provided with a smartphone with software they will use to record performance of a series of motor tasks at, and / or between visits.

Subjects in the Biomarker substudy will have 3mm skin punch biopsies, DaT SPECT, and CSF collected as exploratory measures of PD progression; CSF will be used to measure K0706 level, and frozen for later analysis of emerging biomarkers (e.g., proteins) associated with PD progression and K0706 target engagement.

• The subject has given written informed consent and is willing to participate in the study;
• Subject is able to understand and comply with all study procedures (requires literacy in available language of all patient-reported outcome measures)
• Males or females aged ≥ 50 years
• Body mass index (BMI) greater than 18.5 kg/m2 and less than 45 kg/m2;
• Diagnosed with “Clinically Probable PD” according to the MDS clinical diagnostic criteria, with documented diagnosis of PD per treating physician’s records within three years of the Screening visit. Disease severity according to modified Hoehn & Yahr stage ≤ 2.
• Projected to not require to start dopaminergic therapy within 9 months from Baseline
• Female subjects must be not of childbearing potential, e.g., documented evidence that they are surgically sterile (e.g., hysterectomy, partial hysterectomy, bilateral oophorectomy, bilateral tubal ligation), or post-menopausal (at least 12 months since last menses) prior to Screening with serum Follicular Stimulating Hormone (FSH) ≥40 mIU/mL).
• Male subjects enrolled in the study should not father a child and are advised to prevent passage of semen to their sexual partner during intercourse using an effective method as judged by the Investigator for the duration of the study and for 3 months after the last dose of study drug
• Willingness to undergo lumbar puncture and skin biopsy for future testing of substances related to PD or K0706 target engagement.

Patients with PD will be recruited throughout the US by participating neurologists and health networks as well as the Parkinson’s Foundation. Patients may also self-refer to the study. Interested patients can access study information on a study website (topaz.eurekaplatform.org) as well as through the Parkinson’s Foundation Helpline. Patients who wish to enroll will be directed to an interactive electronic consent (eConsent). Following eConsent, participants complete a screening questionnaire (to confirm eligibility), followed by a baseline questionnaire. If a participant is determined to be eligible following these steps, they may be scheduled for a Telemedicine assessment to further confirm the PD or parkinsonism diagnosis, unless they have been referred directly from a participating neurologist. If confirmed, the participant will be mailed a supply of vitamin D3 800-1000 IU and instructed to take one vitamin D tablet every day for 2 months. Lastly, a Nurse Home Visit will be scheduled and conducted to confirm final eligibility, randomization, and administration of the study drug, if appropriate. Participants who are randomized will be contacted every 4 months for at least 2 years to determine if they have had any fractures.

• Men and women age 60 or older
• Current Parkinson’s Disease or neurodegenerative parkinsonism diagnosis (including progressive supranuclear palsy, multiple system atrophy, cortical basal degeneration, vascular parkinsonism, dementia with Lewy bodies or another form of neurodegenerative parkinsonism)
• Willing and able to continue in follow-up for at least 2 years
• Willing and able to provide informed consent

Participants will undergo screening to evaluate their eligibility to participate in the study to include evaluation of Parkinson’s diagnosis, vital signs, blood chemistry, hematology and urinalysis and complete listing of concomitant medications. Those selected will be enrolled and randomized to one of three active IkT-148009 arms (50/100/200 mg) or a placebo arm (3:1). All clinical staff, study investigators, and participants will be blinded to study assignments throughout the trial.

C3FIT’s overall goal is to assess if patient outcomes are improved when the CSC/PSC system is supplemented with an Integrated Stroke Practice Unit (ISPU) system of care, a patient-centric model of care involving the patient and caregiver/family that coordinates care from the acute management through the rehabilitation and recovery of the patient.

• ​Age 18+.
• Clinical diagnosis of acute stroke with brain imaging compatible with intracerebral hemorrhage or ischemic stroke (including normal brain scan)
• English or Spanish speaking subjects.
• Patient admitted within 7 days of their index stroke event.
• Patient is discharged alive and not to hospice care.
• Patient living at discharge within the geography of recruitment for that C3FIT site.
• Pre-morbid mRS Rankin score of 0-1.
• Patient and/or surrogate give consent to participate after an informed consent process.
• Patients who go to rehabilitation inpatient therapy or other care facilities are eligible, as long as they reside in the geographic are of recruitment and do not go to hospice care.

Visits will include a Screening Visit, Randomization and Baseline Visit, in-person visits at 6, 12, 24 and 36 months and telephone visits at 3, 9, 15, 18, 21, 27, 30, 33 months.

• ​Men and women aged 18 to 60 years.
• Established diagnosis of MS, as defined by the 2017 revision of McDonald Diagnostic Criteria (99).
• Relapsing-remitting multiple sclerosis disease course as defined by the 2013 revisions of the MS clinical course definition (4).
• Participants must have evidence of active disease based on:
  – one or more MS relapses within the last 18 months prior to screening visit or
  – radiological evidence of MS activity (≥2 new T2 lesions within the last 12 months from screening or ≥1 GdE demonstrated on brain or spinal cord MRI performed within the last 12 months of screening).
• Participants must be ambulatory with disease onset ≤ 5 years and treatment-naïve (i.e., no MS disease modifying therapy at any time in the past).
• Participants must be eligible to receive at least one form of disease modifying therapy within each treatment arm
• Kurtzke Expanded Disability Status Scale at Baseline visit ≤ 6.5

All subjects will receive orally administered ozanimod HCl 1 mg. The primary efficacy endpoint is the proportion of subjects with a clinically meaningful increase in raw score of ≥ 4 points or 10% from baseline (improved). The treatment period is 36 months. For all subjects who finish the subject and for those who discontinue, there will be a 30-day (± 15 days) and a 90-day (± 10 days) Safety Follow-up Visit. There is no planned protocol extension following the end of the study. Approximately 250 subjects with RMS will be recruited for this study.

Subjects with RMS will be enrolled in this study if they have received ≤ 1 DMT, have an EDSS ≤ 3.5, and have been diagnosed with RMS within 5 years of study entry.

• Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subject is male or female 18 to 65 years of age (inclusive) at the time of signing of the ICF.
• Subject has a diagnosis of MS according to the 2010 or 2017 Revised McDonald criteria.
• Subject has ≤ 5 years since time of relapsing multiple sclerosis diagnosis.
• Subject has ≤ 1 approved relapsing multiple sclerosis disease modifying therapy at time of study entry.
• Subjects has a disability status at screening with an EDSS (Expanded Disability Status Scale) score  ≤3.5 (inclusive).
• Subject has no history of relapse with onset from 30 days prior to Screening. During this period, subjects must have been clinically stable, without systemic corticosteroid treatment or adrenocorticotrophic hormone (ACTH).
• Subjects must have documentation of positive varicella zoster virus (VZV) immunoglobulin G (IgG) antibody status or complete VZV vaccination at least 30 days prior to enrollment.
• Females of childbearing potential (FCBP) must agree to practice a highly effective method of contraception throughout the study and until completion of the 90-day Safety Follow-up Visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly.

The Core Part is a randomized, double-blind, double-dummy, active comparator-controlled, fixed-dose, parallel-group, multi-center study in approximately 800 participants with relapsing multiple sclerosis (RMS).

The Extension Part is an open-label, single-arm, fixed-dose design in which eligible participants are treated with remibrutinib for up to 5 years.