Background: Adeno-associated virus (AAV)-mediated gene transfer therapy has shown early signs of potential to treat Duchenne Muscular Dystrophy (DMD). The intent of rAAVrh74.MHCK7.micro-dystrophin (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.
We designed an AAV 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 that included 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 included ambulatory boys aged ≥4 to <8 years with a confirmed DMD gene mutation (exons 18–58), an established clinical diagnosis and stable steroid dosing (≥12 weeks). A single-dose (2×1014 vg/kg) SRP-9001 intravenous (IV) infusion treatment arm was compared with a placebo IV infusion arm. Safety endpoints included incidence of serious adverse events and treatment-emergent adverse events (up to Week 260). Primary efficacy endpoints included 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 included Time to Rise, 4-Stair Climb, and 10-Meter and 100-Meter Timed Tests (baseline to Week 48).
Objectives: The purpose of this study is to evaluate the safety and efficacy of IV SRP-9001 in people with DMD by measuring biological and clinical endpoints in a Phase 2 multicenter, randomized, double-blind, placebo-controlled trial (NCT03769116).
Results: Results from the 41 patients that have been randomized and dosed (SRP-9001 or placebo) in Part 1 will be presented.
Conclusions: Initial safety and efficacy findings from this study suggest the potential of SRP-9001 therapy for clinically meaningful functional improvements in people with DMD.
This study was funded by Sarepta Therapeutics, Inc.