A phase 2, randomized, placebo-controlled, multiple ascending-dose study of ACE-031 (ActRIIB-IgG1) in Duchenne muscular dystrophy (DMD): Preliminary results

To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) effects of ACE-031 in boys with DMD. DMD is caused by dystrophin deficiency resulting in progressive muscle weakness. ACE-031 is a fusion protein comprised of the extracellular domain of activin receptor type IIB (ActRIIB) and IgG1 Fc domain, which inhibits myostatin and related proteins that negatively regulate muscle mass. In phase 1 studies in healthy adults, ACE-031 treatment resulted in increased mean muscle mass and decreased mean fat mass. Ambulatory, steroid-treated DMD boys, age P 4 years, were randomized to escalating doses of ACE-031 or placebo (3:1) for 12 weeks, with 12 weeks follow-up. The primary objective of the study was to assess safety and tolerability. PD endpoints included lean, fat, and bone mass (DXA), thigh muscle and fat volume (MRI), strength, motor function, pulmonary function, and bone biomarkers. Preliminary, blinded data for patients enrolled in Cohort 1 (0.5 mg/kg SC q4wk, n = 12) and Cohort 2 (1 mg/kg SC q2wk, n = 12) are presented herein. The mean (±SD) age was 10.3 ± 3.1 years (range 6-17). Most common adverse events (AEs) were injection site erythema (12/24), epistaxis (6/24), vomiting (5/24) and telangiectasias (5/24). There were no serious AEs. Increased lean mass was observed in subjects treated in either cohort. Fat mass and sCTX (a bone resorption marker) tended to increase in subjects in Cohort 1 and decrease in subjects in Cohort 2. Unblinded data, including strength and function, will be presented at meeting. In this phase 2 study in steroid-treated boys with DMD, ACE- 031 was generally well-tolerated; AEs included epistaxis and telangiectasia at the higher dose. Increased lean mass and decreased fat mass were observed at this dose level. These data support further development of ACE-031 as a potential treatment for DMD.