EMBARK, a Phase 3 Trial Evaluating Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Duchenne Muscular Dystrophy (DMD): Study Design and Baseline Characteristics
Francesco Muntoni1, Eugenio Mercuri2, Ulrike Schara Schmidt3, Hirofumi Komaki4, James Richardson5, Tejdip Singh5, Maitea Guridi6, Stefanie Mason5, Alex Murphy6, Lixi Yu5, Carol Reid7, Eddie Darton5, Christoph Wandel6, Jerry Mendell8
1The Dubowitz Neuromuscular Centre, NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health University College London, & Great Ormond Street Hospital Trust, 2Pediatric Neurology Institute, Catholic University and Nemo Pediatrico, Fondazione Policlinico Gemelli IRCCS, 3Department of Pediatric Neurology, Center for Neuromuscular Disorders in Children and Adolescents, University Clinic Essen, University of Duisburg-Essen, 4Translational Medical Center, National Center of Neurology and Psychiatry, 5Sarepta Therapeutics, Inc., 6F. Hoffmann-La Roche Ltd, 7Roche Products Ltd, 8Center for Gene Therapy, Nationwide Children’s Hospital
Objective:
To describe the EMBARK (Study 301; NCT05096221) study design, a Phase 3, global, randomized, double-blind, two-part, placebo-controlled study assessing the safety and efficacy of intended commercial process delandistrogene moxeparvovec (SRP-9001) material in ambulatory individuals with a confirmed Duchenne muscular dystrophy (DMD) mutation within exons 18─79 (excluding individuals with a mutation fully contained within exon 45), aged ≥4 to <8 years (N=125).
Background:
Delandistrogene moxeparvovec is an investigational gene transfer therapy developed to address the root cause of DMD through targeted skeletal and cardiac muscle expression of SRP-9001 dystrophin protein, which contains key functional domains of dystrophin.
Design/Methods:
In Part 1, participants will be stratified by age at randomization (≥4 to <6 years or ≥6 to <8 years) and North Star Ambulatory Assessment total score (NSAA ≤22 points or >22 points) at screening and randomized (1:1) to receive a single intravenous dose of intended commercial process delandistrogene moxeparvovec material (1.33x1014 vg/kg by linear standard qPCR) or placebo. Participants will be evaluated at Week 52. In Part 2 (52-week follow-up period), participants randomized to placebo in Part 1 will receive delandistrogene moxeparvovec and participants randomized to delandistrogene moxeparvovec in Part 1 will receive placebo.
The primary endpoint is change from baseline to Week 52 in NSAA total score (Part 1). Secondary endpoints include safety; SRP-9001 dystrophin protein production at Week 12 by western blot and change from baseline to Week 52 in: key timed function tests, stride velocity 95th centile measured by a wearable device, and Patient-Reported Outcomes Measurement Information Score®.
Results:
For the first time, we present baseline characteristics of participants enrolled in EMBARK, a Phase 3 study of delandistrogene moxeparvovec.
Conclusions:
EMBARK will provide placebo-controlled information about efficacy and safety of delandistrogene moxeparvovec in a large population of ambulatory patients with DMD aged ≥4 to <8 years.