EMBARK study design: Phase 3 trial evaluating the safety and efficacy of delandistrogene moxeparvovec (SRP-9001) in Duchenne muscular dystrophy


Clinical Trials

Poster Number: 28


Francesco Muntoni, MD, Great Ormond Street Institute of Child Health, London, UK, Eugenio Mercuri, Paediatric Neurology and Centro Clinico Nemo, Catholic University and Policlinico Gemelli, Fondazion, Ulrike Schara-Schmidt, University Clinic Essen, University of Duisburg-Essen, Hirofumi Komaki, MD, PhD, National Center of Neurology and Psychiatry, Tokyo, Japan, James Richardson, Sarepta Therapeutics, Inc, Teji Singh, MD, Sarepta Therapeutics, Maitea Guridi, F. Hoffmann-La Roche Ltd, Stefanie Mason, Sarepta Therapeutics, Alex Murphy, F. Hoffmann-La Roche Ltd, Larry Hu, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Carol Reid, Roche Products Ltd, Eddie Darton, Sarepta Therapeutics, Inc., Christoph Wandel, F. Hoffmann-La Roche Ltd, Jerry Mendell, MD, Nationwide Children’s Hospital

Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy developed for targeted skeletal and cardiac muscle expression of micro-dystrophin, a shortened, functional dystrophin protein. Patients with Duchenne muscular dystrophy (DMD) in Cohort 1 of the Phase 1b study (ENDEAVOR, Study 103; NCT04626674) who were treated with commercially representative delandistrogene moxeparvovec material demonstrated micro-dystrophin protein expression, with an acceptable safety profile. These results are in line with findings from previous studies that used clinical process delandistrogene moxeparvovec material (Study 101; NCT03375164 and Study 102; NCT03769116). Objectives: EMBARK (Study 301; NCT05096221) is a Phase 3, global, randomized, double-blind, two-part, placebo-controlled study assessing the safety and efficacy of commercially representative delandistrogene moxeparvovec material in ambulatory boys with a confirmed DMD mutation within exons 18?44 or 46?79, aged ?4 to <8 years old (target enrollment: N=120). Results: Participants in Part 1 (52-week follow-up period) will be randomized (1:1) to delandistrogene moxeparvovec or placebo arms, according to age at randomization (>4 to <6 years vs. >6 to <8 years) and baseline North Star Ambulatory Assessment total score (NSAA <22 points vs. >22 points). Participants will receive a single, intravenous 1.33×1014 vg/kg (linear standard qPCR) dose of commercially representative delandistrogene moxeparvovec material or placebo. In Part 2 (52-week follow-up period), patients randomized to placebo in Part 1 will receive delandistrogene moxeparvovec. The primary endpoint will assess the change in NSAA total score from baseline to Week 52 (Part 1). Secondary endpoints include micro-dystrophin protein expression at Week 12 measured by western blot; the number of skills gained or improved at Week 52 measured by NSAA; change from baseline to Week 52 in: timed function tests (Time to Rise, 100-Meter and 10-Meter Walk/Run, 4-Stair Climb), stride velocity 95th centile measured by a wearable device, and Patient-Reported Outcomes Measurement Information Score®; and safety outcome measures. Conclusions: EMBARK will provide pivotal information about efficacy and safety of investigational delandistrogene moxeparvovec therapy in a large population of ambulatory patients with DMD. This study is sponsored by Sarepta Therapeutics & funded by Sarepta Therapeutics & F. Hoffmann-La Roche.