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

Abstract

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.

• Authors: Kathryn R Wagner, Hoda Z Abdel-Hamid, Jean K Mah, Craig Campbell, Michela Guglieri, Francesco Muntoni, Yasuhiro Takeshima, Craig M McDonald, Anna Kostera-Pruszczyk, Peter Karachunski, Russell J Butterfield, 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
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 30 Issue 6 Pg. 492-502 (06 2020) ISSN: 1873-2364 [Electronic] England
• PMID: 32522498 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Myostatin
• domagrozumab

Topics

• Adolescent
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects, blood, pharmacology)
• Child
• Exercise Test
• Humans
• Male
• Muscular Dystrophy, Duchenne (drug therapy)
• Myostatin (antagonists & inhibitors)
• Outcome Assessment, Health Care
• Treatment Failure