hope-duchenne (halt cardiomyopathy progression in duchenne)

Conditions: Duchenne Muscular Dystrophy; Cardiomyopathy

Summary: male participants with cardiomyopathy secondary to duchenne muscular dystrophy (dmd) meeting all inclusion and no exclusion criteria will be randomized. all participants will be at least 12 years of age. they will be randomized in a 1:1 manner to either intracoronary infusion of cap-1002 in three coronary arteries supplying the three major cardiac territories of the left ventricle of the heart (anterior, lateral, inferior/posterior) or usual care. in the active treatment arm, all three major cardiac territories will be treated (infused) during a single procedure in an open-label fashion.

approximately 24, and not more than 30, participants will be randomized into the study, in two sequential enrollment groups. safety data from group 1 will undergo a data safety monitoring board (dsmb) review prior to initiation of enrollment for group 2. the first 6-8 randomized participants will comprise group 1, and will include a minimum of 3 participants completing intracoronary infusion with cap-1002. the dsmb will conduct a review of interim safety data through 72 hours post-day 0 for at least 3 infused participants and for at least 6 participants overall. enrollment of group 2 will begin per dsmb recommendations following their review of the 72 hour safety data from group 1. group 2 will include approximately 18 participants. screening and randomization will continue until at total of 12 participants are infused with cap 1002 or 30 participants are randomized into the study, whichever comes first. all participants assigned to the active treatment arm will receive an intended total dose of up to 75 million (m) cap-1002 cells infused as 25m cells into each of the three left ventricle cardiac territories (anterior, lateral, inferior/posterior). participants randomized to receive usual care will continue to be cared for and treated in whatever manner the investigator deems most appropriate for the participant on an ongoing basis, and will receive no infusion. randomization will take place within 30 days of the first screening procedure. after completion of the screening procedures, eligible participants randomized to active treatment arm will receive cap-1002 administered via intracoronary infusion on day 0. day 0 for eligible participants randomized to the usual care arm will occur 7 days after the date of randomization. all randomized participants will have a follow-up telephone call on study day 3, and study visits at weeks 2 and 6, and at months 3, 6 and 12 post day 0.

Eligibility criteria:
inclusion criteria: 1. male participants 18 years of age or older must be able to provide informed consent and follow up with protocol procedures. male participants at least 12 years of age but younger than 18 years of age must be able to provide assent with parent or guardian providing permission for study participation. only male participants will be randomized into this study. 2. documented diagnosis of duchenne muscular dystrophy by genetic mutation analysis. 3. cardiomyopathy with left ventricular scar by late gadolinium enhancement (lge) in at least 4 segments as assessed by contrast-enhanced mri and ef \>35% at the time of screening. 4. use of evidence based medical-therapy in accordance with the "dmd care considerations working group" guidelines for the management of dmd, for at least three months prior to signing the consent form (or, providing assent) or documented contraindication or intolerance or patient preference. 5. participants must be taking systemic glucocorticoids for at least six months prior to screening. 6. participants must be 12 years of age or older at time of screening 7. participants must be appropriate candidates for cardiac catheterization and intracoronary infusion of cap-1002, in the judgement of the site's interventional cardiologist. exclusion criteria: 1. therapy with intravenous inotropic or vasoactive medications at the time of screening. 2. inability to undergo cardiac catheterization and/or mri without general anesthesia. 3. immunologic incompatibility with all available master cell banks (mcbs) by single-antigen bead (sab) serum antibody profiling. 4. planned or likely major surgery in the next 12 months after planned randomization. 5. left ventricular assist devices (lvad) or those subjects actively in the process of acquiring a lvad. 6. contraindication to cardiac mri. 7. known hypersensitivity to contrast agents. 8. estimated glomerular filtration rate (gfr) \<60 ml/min, as calculated by the ckd-epi cystatin c equation (inker, schmid et al. 2012). 9. active infection not responsive to treatment. 10. active systemic allergic reaction(s), connective tissue disease or autoimmune disorder(s). 11. history of cardiac tumor or cardiac tumor demonstrated on screening mri. 12. history of previous stem cell therapy. 13. history of use of medications listed in appendix 3 within 3 months prior to signing the inform consent form / assent through completion of the study infusion. 14. known moderate-to-severe aortic stenosis/insufficiency or severe mitral stenosis/regurgitation. 15. current active alcohol or drug abuse. 16. known history of human immunodeficiency virus (hiv) infection. 17. known history of chronic viral hepatitis. 18. abnormal liver function (alanine aminotransferase (alt)/aspartate aminotransferase (ast) \>10 times the upper reference range) and/or abnormal hematology (hematocrit \<25%, white blood cells \<3000 μl, platelets \<100,000 μl) studies without a reversible, identifiable cause. 19. known hypersensitivity to bovine products. 20. known hypersensitivity to dimethyl sulfoxide (dmso). 21. uncontrolled diabetes (hba1c \>9.0). 22. inability to comply with protocol-related procedures, including required study visits. 23. any condition or other reason that, in the opinion of the investigator or medical monitor, would render the subject unsuitable for the study. 24. currently receiving investigational treatment on another clinical study or expanded access protocol, including any of the following: * received investigational intervention within 30 days prior to randomization * treatment and/or an incomplete follow-up to treatment with any investigational cell based therapy within 6 months prior to randomization * active participation in other research therapy for cardiovascular repair/regeneration

Keywords: duchenne muscular dystrophy cardiomyopathy