Randomized phase 2 study of ACE‐083, a muscle‐promoting agent, in facioscapulohumeral muscular dystrophy

Introduction/Aims Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE‐083 could safely increase muscle volume and improve functional outcomes in adults with FSHD. Methods Participants were at least 18 years old and had FSHD1/FSHD2. Part 1 was open label, ascending dose, assessing safety and tolerability (primary objective). Part 2 was randomized, double‐blind for 6 months, evaluating ACE‐083240 mg/muscle vs placebo injected bilaterally every 3 weeks in the biceps brachii (BB) or tibialis anterior (TA) muscles, followed by 6 months of open label. Magnetic resonance imaging measures included total muscle volume (TMV; primary objective), fat fraction (FF), and contractile muscle volume (CMV). Functional measures included 6‐minute walk test, 10‐meter walk/run, and 4‐stair climb (TA group), and performance of upper limb midlevel/elbow score (BB group). Strength, patient‐reported outcomes (PROs), and safety were also evaluated. Results Parts 1 and 2 enrolled 37 and 58 participants, respectively. Among 55 participants evaluable in Part 2, the least‐squares mean (90% confidence interval, analysis of covariance) treatment difference for TMV was 16.4% (9.8%‐23.0%) in the BB group (P