A Phase 2, Randomized, Placebo-Controlled, Multiple Ascending-Dose Study of ACE-031, a Soluble Activin Receptor Type IIB, in Boys with Duchenne Muscular Dystrophy (DMD) (P04.088)

Objective: To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic (PD) effects of ACE-031 in DMD. Background ACE-031 is a soluble activin type IIB receptor (ActRIIB-IgG1) that binds negative regulators of muscle, including myostatin and activin. In phase 1 studies in healthy adults, ACE-031 treatment resulted in dose-dependent increases in lean mass. Design/Methods: Ambulatory (30ft walk/run Results: Two cohorts completed treatment (C1: 0.5mg/kg SC q4weeks, C2: 1mg/kg SC q2weeks). Mean age was 10.3 years (range 6-17). There were no AEs that were serious, severe, or resulted in discontinuation. Reversible telangiectasias and mild epistaxis were reported in C2. Mean total body lean mass by DXA increased 5.2% in C2 (p=0.015 vs baseline) vs 2.6% in placebo (p=0.20) after 12 weeks. Thigh MRI (C2) showed a trend for decreased muscle volume in placebo group which was attenuated in ACE-031 group. The least-squares mean Δ6MWD was +12meters in combined ACE-031 groups vs -30meters in placebo group after 24 weeks (p=0.06, ANCOVA). The %change in 6MWD correlated with that for 2MWD (r=0.67, p Conclusions: In this phase 2 study of ACE-031 in steroid-treated DMD boys, reversible telangiectasias and mild epistaxis were reported at higher dose. Significant dose-dependent increases in lean mass were observed. There were trends for maintained 6MWD, decreased gain in fat mass, and increased lumbar spine BMD with ACE-031 treatment. Supported by: MDA, PPMD. Disclosure: Dr. Campbell has received research support from Acceleron Pharma and PTC Therapeutics. Dr. Escolar has received personal compensation for activities with Acceleron Pharma as a consultant. Dr. Mah has received research support from Acceleron Pharma Inc. and PTC Therapeutics. Dr. Tarnopolsky has received personal compensation for activities with Genzyme Corporation as a speaker. Dr. Tarnopolsky has received research support from Genzyme Corporation. Dr. Selby has received research support from Acceleron Pharma. Dr. McMillan has nothing to disclose. Dr. Yang has received personal compensation for activities with Acceleron Pharma as an employee. Ms. Wilson has received personal compensation for activities with Acceleron Pharmaceuticals as an employee. Ms. Barger has received personal compensation for activities with Acceleron Pharma as an employee. Dr. Sherman has received personal compensation for activities with Acceleron Pharma as an employee. Dr. Sherman holds stock and/or stock options in Acceleron Pharma. Dr. Attie has received personal compensation for activities with Acceleron Pharma as an employee.