Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy

• DOI: 10.1016/j.nmd.2020.05.002
• Publication Date: 2020-05-19T06:36:44Z
• Authors: Kathryn R. Wagner; Hoda Z. Abdel-Hamid; Jean K. Mah; Craig Campbell; Michela Guglieri; Francesco Muntoni; Yasuhiro Takeshima; Craig M. McDonald; Anna Kostera-Prus...; Peter Karachunski; Russell J. Butter...; Eugenio Mercuri; Chiara Fiorillo; Enrico S. Bertini; Cuixia Tian; Jeffery Statland; Alesia B. Sadosky; Vivek S. Purohit; Sarah P. Sherlock; Jeffrey P. Palmer; Michael Binks; Lawrence Charnas; Shannon Marraffino; Brenda L. Wong
• Keywords: Duchenne muscular dystrophy; Male; 0301 basic medicine; Adolescent; 610; Myostatin; Antibodies, Monoclonal, Humanized; Pediatrics; 3. Good health; Muscular Dystrophy, Duchenne; 03 medical and health sciences; myostatin inhibitor; 4-stair climb; Outcome Assessment, Health Care; Exercise Test; Humans; Treatment Failure; domagrozumab; Child

We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to <16 years) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49. Secondary endpoints included other functional tests, pharmacokinetics, and pharmacodynamics. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in domagrozumab- and placebo-treated patients, respectively. Difference in mean (95% CI) change from baseline in 4SC at week 49 for domagrozumab vs placebo was 0.27 (-7.4 to 7.9) seconds (p = 0.94). There were no significant between-group differences in any secondary clinical endpoints. Most patients had ≥1 adverse event in the first 48 weeks; most were mild and not treatment-related. Median serum concentrations of domagrozumab increased with administered dose within each dose level. Non-significant increases in muscle volume were observed in domagrozumab- vs placebo-treated patients. Domagrozumab was generally safe and well tolerated in patients with DMD. Efficacy measures did not support a significant treatment effect. Clinicaltrials.gov identifiers: NCT02310763 and NCT02907619.