A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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HOPE-2 is a double-blind clinical trial evaluating the safety and efficacy of a cell therapy called CAP-1002 in study participants with Duchenne muscular dystrophy (DMD). Non-ambulatory and ambulatory boys and young men who meet eligibility criteria will be randomly assigned to receive either CAP-1002 or placebo every 3 months for a total of 4 doses during a 12-month period.

Detailed Description
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Approximately 84 eligible study participants will be randomized to either CAP-1002 or placebo in a 1:1 ratio. The trial will include visits at Screening, Baseline/Day 1, Week 4, and Months 3, 6, 9, and 12 with IV infusions of CAP-1002 or placebo on Day 1 and Months 3, 6, and 9. Safety evaluations will include adverse events, concomitant medications, physical exam, vital signs, 12-lead ECG, and clinical laboratory testing. Efficacy will be evaluated in the Performance of the Upper Limb, pulmonary function testing, North Star Ambulatory Assessment (ambulatory subjects only), strength testing, cardiac MRI, and quality of life. If trial data suggests an appropriate risk/benefit profile of CAP-1002, Capricor, upon the recommendation of the Data Safety Monitoring Board (DSMB), will introduce an open-label extension study to offer CAP-1002 to study participants who were randomized to placebo and completed all trial visits during the 12-month period.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Intravenous Delivery of Allogeneic Cardiosphere-Derived Cells in Subjects With Duchenne Muscular Dystrophy

Conditions
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Muscular Dystrophies, Muscular Dystrophy, Duchenne, Muscular Disorders, Atrophic, Muscular Diseases, Neuromuscular Diseases, Nervous System Diseases, Genetic Diseases, X-Linked, Genetic Diseases, Inborn

Intervention / Treatment
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* Biological: CAP-1002
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genetically confirmed DMD Reduced upper arm strength as measured by the Performance of Upper Limb Reduced ability to walk/run (if ambulatory) Treatment with systemic glucocorticoids for at least 12 months and at a stable dose at least 6 months prior to study participation, except for weight-based or toxicity-related adjustments Current and up-to-date immunizations Exclusion Criteria: Left ventricular ejection fraction < 35% BMI > 45 Ambulant if ≥ 18 years of age Exon 44 skip-amenable mutation(s) in the DMD gene Deletion mutation(s) encompassing exons 3-7 of the DMD gene Percent-predicted forced vital capacity (FVC) < 35% Chronic respiratory disease not related to DMD (for example, asthma, bronchitis, and tuberculosis) History of diabetes requiring treatment with metformin or insulin within 3 months prior to randomization Treatment with an FDA-approved exon skipping therapy for the treatment of DMD if on a stable dose for less than 24 months prior to randomization Treatment with human growth hormone (HGH) within 3 months prior to randomization, unless on a stable dose for at least 24 months prior to randomization Treatment with idebenone within 3 months prior to randomization Treatment with a cell therapy product within 12 months prior to randomization Treatment with an investigational product within 6 months prior to randomization

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAP-1002<br>Patients will receive 150 million cardiosphere-derived cells (CDCs) via intravenous infusion every 3 months for a total of 4 doses. | Biological: CAP-1002<br>* The active pharmaceutical ingredient in CAP-1002 is Cardiosphere-Derived Cells (CDCs). CDCs are known to secrete numerous bioactive elements (growth factors, exosomes) which impact the therapeutic benefits of the cell-based therapy. The mechanism of action is the composite ability to be immunomodulatory, anti-fibrotic and regenerative.<br>* Other names: CDCs;|
| Placebo Comparator: Placebo<br>Patients will receive a placebo solution via intravenous infusion every 3 months for a total of 4 doses. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the mid-level (elbow) dimension of the Performance of the Upper Limb (PUL) | The PUL includes functional tasks that relate to activities of daily living that are very important for quality of life. The PUL has been validated for the assessment of upper limb motor function in individuals with DMD. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the mid-level (elbow) dimension of the PUL | The PUL includes functional tasks that relate to activities of daily living that are very important for quality of life. The PUL has been validated for the assessment of upper limb motor function in individuals with DMD. | Months 3, 6, and 9 | 
| Change in regional systolic left ventricular wall thickening as assessed by cardiac MRI | Systolic thickening is thought to be a principal mechanism of cardiac output generation in people with DMD. | Months 6 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duchenne Muscular Dystrophy, Cell Therapy, Performance of the Upper Limb, Pulmonary Function, Ambulatory, Non-Ambulatory, Glucocorticoids