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Muscle Nerve. 2017 Apr;55(4):458-464. doi: 10.1002/mus.25268. Epub 2016 Dec 23.

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

Author information

1
Pediatrics, Epidemiology and Clinical Neurological Sciences, Western University, London, Ontario, Canada.
2
Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
3
Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada.
4
McMaster University Medical Centre, Hamilton, Ontario, Canada.
5
British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
6
Acceleron Pharma, Cambridge, Massachusetts, USA.
7
Kennedy Krieger Institute, Johns Hopkins Medical School, Baltimore, Maryland, USA.

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.

KEYWORDS:

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

PMID:
27462804
DOI:
10.1002/mus.25268
[Indexed for MEDLINE]

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