Modulation of SERCA2a of Intra-Myocytic Calcium Trafficking in Cardiomyopathy Secondary to Duchenne Muscular Dystrophy

Phase 1

Not yet recruiting

Brief Summary: This research study is testing whether an experimental drug, called SRD-001, is safe and helps the weakened heart of patients with Duchenne muscular dystrophy (DMD) regain its ability to effectively pump blood to the rest of the body. SRD-001 is a form of gene therapy. The goal of SRD-001 gene therapy is to provide the heart muscle cells with extra copies of the SERCA2a gene so that they can produce more SERCA2a protein to help the heart muscle cells squeeze/contract better. Researchers will compare SRD-001 treated participants with no-treatment participants; all participants will continue to take their current heart medications. All participants will be followed very closely for 2 years and undergo cardiac magnetic resonance imaging of their heart at baseline, year 1 and year 2 along with assessment of upper limb function and lung function. After the 2 years of close follow-up, all participants will roll over into long-term follow-up where they will be called biannually for information on their current medical status.

Detailed Description: This phase 1b, multi-center, non-randomized, open-label, ascending dose escalation, no-intervention-control trial will assess the safety and explore the efficacy of SRD-001 administered as a one-time antegrade epicardial coronary artery infusion for the treatment of participants with cardiomyopathy secondary to DMD. SRD-001 is an AAV1 vector expressing the transgene for SERCA2a. Twelve participants will be assigned to either active treatment with SRD-001 or no-intervention based upon their neutralizing antibody status. The objectives of the trial are (1) to evaluate the safety of a one-time intracoronary administration of SRD-001 in participants with cardiomyopathy due to DMD; and (2) to explore the impact of SRD-001 on heart and skeletal muscle function and quality of life. After screening to determine eligibility, participants will be sequentially assigned to low dose SRD-001, high dose SRD-001 or no-intervention. Participants assigned to active treatment with SRD-001 will under cardiac catheterization and angiography just prior to the intracoronary infusion of SRD-001 and spend overnight int he hospital for observation.

Recruitment & Eligibility

Inclusion Criteria

Diagnosis of DMD with confirmatory genetic testing
Cardiomyopathy with left ventricular scar in at least 3 of 16 segments
Left ventricular ejection fraction < 40%
Individualized, optimized cardiac medical therapy and glucocorticoid treatment for at least 12 months prior to enrollment
Willing and able to provide informed consent

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Low Dose	SRD-001	SRD-001
High Dose	SRD-001	SRD-001

Primary Outcome Measures

Name	Time	Method
Rate of all-cause mortality	From Day 1 to Week 52 and Week 104	Death
Rate and severity of related treatment-emergent adverse events	From Day 1 to Week 52 and Week 104	Adverse events related to the investigational product or the administration procedure
Rate and severity of all treatment-emergent adverse events	From Day 1 to Week 52 and Week 104	Adverse events
Rate of cell-mediated immune reaction	From Day 1 to Week 52	Cell-mediated immune reaction as assessed by enzyme-linked immunosorbent spot (ELISpot)

Secondary Outcome Measures

Name	Time	Method
Change, including normal/abnormal shifts, in 12-lead electrocardiogram (ECG)	From Day 1 to Week 52 and Week 104	Change in the heart's electrical activity
Change, including normal/abnormal shifts, in laboratory evaluations	From Day 1 to Week 52 and Week 104	Hematology, serum chemistries, urinalysis, cardiac enzymes and anti-AAV1 antibodies

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