Abstract Details

Adeno-associated virus (AAV)-mediated gene transfer therapy has shown early signs of potential to treat DMD. The intent of SRP-9001 is to safely express a functional micro-dystrophin protein in skeletal and cardiac muscle. Preclinical studies and Phase 1b/2 clinical trial findings warrant further investigation of gene transfer therapy in DMD.

The purpose of this study is to evaluate the safety and efficacy of intravenous rAAVrh74.MHCK7.micro-dystrophin (SRP-9001) in patients with Duchenne muscular dystrophy (DMD) by measuring biological and clinical endpoints in a Phase 2 randomized, double-blind, placebo-controlled trial (NCT03769116).

We designed an adeno-associated virus vector (rAAVrh74) containing a codon-optimized human micro-dystrophin transgene driven by a muscle-specific promoter with a cardiac enhancer, MHCK7, to be tested in a 3-part Phase 2 clinical trial: two 48-week randomized, double-blind, placebo-controlled periods (Part 1 and 2) and an up to 212-week open-label follow-up period (Part 3). Key eligibility criteria: ambulatory boys age ≥4 to <8 years with confirmed DMD gene mutation (exons 18-58); established clinical diagnosis; and stable steroid dosing (≥12 weeks). A single-dose SRP-9001 IV infusion treatment arm will be compared with a placebo IV infusion arm. Safety endpoints include: incidence of serious AEs and treatment-emergent AEs (up to Week 260). Primary efficacy endpoints: change in micro-dystrophin expression (baseline to Week 12); and change in functional outcomes by North Star Ambulatory Assessment (baseline to Week 48). Secondary endpoints include: Time to Rise, 4-Stair Climb, and 10m and 100m timed tests (baseline to Week 48).

Results from the 41 patients that have been randomized and dosed (SRP-9001 or placebo) in Part 1 will be presented.

Initial safety and efficacy findings from this study suggest the potential of SRP-9001 therapy for clinically meaningful functional improvements in patients with DMD.