Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial

Craig Campbell, Hugh J. McMillan, Jean K. Mah, Mark Tarnopolsky, Kathryn Selby, Ty McClure, Dawn M. Wilson, Matthew L. Sherman, Diana Escolar, Kenneth M. Attie

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: ACE-031 is a fusion protein of activin receptor type IIB and IgG1-Fc, which binds myostatin and related ligands. It aims to disrupt the inhibitory effect on muscle development and provide potential therapy for myopathies like Duchenne muscular dystrophy (DMD). Methods: ACE-031 was administered subcutaneously every 2–4 weeks to DMD boys in a randomized, double-blind, placebo-controlled, ascending-dose trial. The primary objective was safety evaluation. Secondary objectives included characterization of pharmacokinetics and pharmacodynamics. Results: ACE-031 was not associated with serious or severe adverse events. The study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias. A trend for maintenance of the 6-minute walk test (6MWT) distance in the ACE-031 groups compared with a decline in the placebo group (not statistically significant) was noted, as was a trend for increased lean body mass and bone mineral density (BMD) and reduced fat mass. Conclusion: ACE-031 use demonstrated trends for pharmacodynamic effects on lean mass, fat mass, BMD, and 6MWT. Non–muscle-related adverse events contributed to the decision to discontinue the study. Myostatin inhibition is a promising therapeutic approach for DMD. Muscle Nerve 55: 458–464, 2017.

Original languageEnglish (US)
Pages (from-to)458-464
Number of pages7
JournalMuscle and Nerve
Volume55
Issue number4
DOIs
StatePublished - Apr 1 2017

Keywords

  • 6-minute walk test
  • Duchenne muscular dystrophy
  • TGF-β superfamily
  • lean body mass
  • myostatin inhibitor
  • placebo-controlled clinical trial

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

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