EMBARK, a Phase 3 trial evaluating safety and efficacy of delandistrogene moxeparvovec in DMD: Study design and baseline characteristics

Topic:

Clinical Trials

Poster Number: 100

Author(s):

Francesco Muntoni, MD, UCL Institute of Child Health and Great Ormond Street Hospital for Children, Eugenio Mercuri, MD, PhD, Department of Paediatric Neurology and Nemo Clinical Centre, Catholic University, Ulrike Schara-Schmidt, University Clinic Essen, University of Duisburg-Essen, Hirofumi Komaki, MD, PhD, Translational Medical Center, National Center of Neurology and Psychiatry, James Richardson, Sarepta Therapeutics, Inc., Teji Singh, MD, Sarepta Therapeutics, Inc., Maitea Guridi, F. Hoffman-La Roche Ltd, Stefanie Mason, Sarepta Therapeutics, Inc., Alex Murphy, F. Hoffman-La Roche Ltd, Lixi Yu, Sarepta Therapeutics, Inc., Carol Reid, Roche Products Ltd, Eddie Darton, Sarepta Therapeutics, Inc., Christoph Wandel, F. Hoffman-La Roche Ltd, Jerry Mendell, MD, Nationwide Children's Hospital

Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy developed to address the root cause of Duchenne muscular dystrophy (DMD) through targeted skeletal and cardiac muscle expression of SRP-9001 dystrophin protein, which contains key functional domains of dystrophin. Objective: To describe the design of EMBARK (Study 301; NCT05096221), a Phase 3, global, randomized, double-blind, two-part, placebo-controlled study assessing the safety and efficacy of intended commercial process delandistrogene moxeparvovec material in ambulatory individuals with a confirmed DMD mutation within exons 18─79 (excluding individuals with a mutation fully contained within exon 45), aged ≥4 to <8 years (N=125). Methods: In Part 1, participants will be stratified by age (≥4 to <6 years or ≥6 to <8 years) and North Star Ambulatory Assessment (NSAA) total score (≤22 points or >22 points) at screening and randomized (1:1) to receive a single intravenous dose of intended commercial process delandistrogene moxeparvovec material (1.33×1014 vg/kg by linear standard quantitative polymerase chain reaction) 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 (Part 1); and change from baseline to Week 52 (Part 1) in: key timed function tests, stride velocity 95th centile measured by a wearable device, and Patient-Reported Outcomes Measurement Information Score® (mobility and upper extremity function). Results: We present baseline characteristics of participants enrolled in EMBARK, a Phase 3 study of delandistrogene moxeparvovec. Conclusions: EMBARK will provide placebo-controlled information on the efficacy and safety of delandistrogene moxeparvovec in a large population of ambulatory patients with DMD aged ≥4 to <8 years. This study was sponsored by Sarepta Therapeutics and funded by Sarepta Therapeutics and F. Hoffmann-La Roche Ltd.