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

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

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.

• Approximately 20 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 by Performance of the Upper Limb, cardiac MRI, pulmonary function testing, North Star Ambulatory Assessment (ambulatory subjects only), strength testing, 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.

Inclusion Criteria:

1. Male participants at least 10 years of age at time of consent
2. Participants willing and able to provide informed consent to participate in the trial if >= 18 years of age, and assent with parental or guardian informed consent if < 18 years of age
3. Participants with diagnosis of DMD based on clinical and phenotypic manifestations consistent with DMD (e.g., family history of DMD, elevated creatine kinase, dystrophin muscle biopsy, calf pseudohypertrophy, Gowers' sign, and gait impairment before 7 years of age) with confirmatory genetic testing performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
4. Participants with performance of the Upper Limb entry item score 2-5
5. Participants if ambulatory, 10-meter walk/run velocity < 1 meter/second
6. Participants with loss of independent ambulation by 18th birthday (standing unassisted or ability to take, at most, several steps independently is not considered ambulation)
7. Participants who receiving standard of care therapy at an experienced, multidisciplinary, DMD center as evidenced by regular cardiac and pulmonary monitoring, systemic glucocorticoid treatment, and at-home range of motion exercises
8. Participants who received treatment with a systemic glucocorticoid is required for at least 12 months prior to randomization. The dose must remain stable for at least 6 months prior to randomization with the exception of either weight-based dose adjustment or a decrease in steroid dose of ≤ 10% for toxicity. For patients on chronic deflazacort, treatment with an equivalent dose of prednisone or prednisolone for a period of ≤ 30 days to bridge lack of availability of deflazacort during the 6 months prior to randomization is acceptable
9. Participants with current and up-to-date immunizations according to children and adolescent Centers for Disease Control immunization schedule, unless contraindicated, including the following: meningococcal and meningococcal B; tetanus, diphtheria & acellular pertussis (Tdap); and pneumococcal polysaccharide vaccinations
10. Participants with adequate venous access for parenteral IP infusions and routine blood collections in the judgement of the Investigator
11. Participants assessed by the Investigator as willing and able to comply with the requirements of the trial

Exclusion Criteria:

1. Participants with Left Ventricular Ejection Fraction (LVEF) < 35%
2. Participants with elbow-flexion contractures > 30° in both extremities
3. Participants with Body Mass Index (BMI) > 45
4. Participants with documentation of exon 44 skip-amenable mutation(s) in the dystrophin gene
5. Participants with documentation of dystrophin deletion mutation(s) encompassing and limited to exons 3-7
6. Participants with percent predicted FVC (FVC%p) < 35%
7. Participants with inability to perform consistent FVC measurement within ±15% during paired testing at screening
8. Participants with risk of near-term respiratory decompensation in the judgment of the investigator, or the need for initiation of non-invasive ventilator support as defined by serum bicarbonate ≥ 29 mmol/L at screening
9. Participants with history of non DMD-related chronic respiratory disease requiring ongoing or intermittent treatment, including, but not limited to, asthma, bronchitis, and tuberculosis
10. Participants with acute respiratory illness within 30 days prior to screening
11. Participants with initiation of non-invasive ventilation within 30 days prior to screening, or the anticipated need to initiate non-invasive ventilation within the 12 months following screening
12. Participants with planned or anticipated thoracic or spinal surgery within the 12 months following randomization
13. Participants with planned or anticipated lower extremity surgery within the 12 months following randomization, if ambulatory
14. Participants with known hypersensitivity to Dimethyl Sulfoxide (DMSO) or bovine products
15. Participants with initiation of treatment with metformin or insulin within 3 months prior to randomization
16. Participants with initiation of treatment with an FDA-approved exon skipping therapy for the treatment of DMD within 24 months prior to randomization or dose adjustments to the therapy within 12 months prior to randomization with the exception of weight-based dose adjustments.
17. Participants who received treatment with Human Growth Hormone (HGH) within 3 months prior to randomization, unless on a stable dose (as determined by the site PI) for at least 24 months prior to randomization
18. Participants who received Treatment with idebenone within 3 months prior to randomization
19. Participants who received treatment with a cell therapy product within 12 months prior to randomization
20. Participants who received treatment with an investigational product within 6 months prior to randomization
21. Participants with history, or current use, of drugs or alcohol that could impair their ability to comply with participation in the trial
22. Participants with inability to comply with the investigational plan and follow-up visit schedule for any reason, in the judgment of the investigator