Randomized Phase 2 Study of ACE-083, a Muscle-Promoting Agent, in Facioscapulohumeral Muscular Dystrophy

Jeffrey M Statland; Craig Campbell; Urvi Desai; Chafic Karam; Jordi Díaz-Manera; Jeffrey T Guptill; Lawrence Korngut; Angela Genge; Rabi N Tawil; Lauren Elman; Nanette C Joyce; Kathryn R Wagner; Georgios Manousakis; Anthony A Amato; Russell J Butterfield; Perry B Shieh; Matthew Wicklund; Josep Gamez; Cynthia Bodkin; Alan Pestronk; Conrad C Weihl; Juan J Vilchez-Padilla; Nicholas E Johnson; Katherine D Mathews; Barry Miller; Ashley Leneus; Marcie Fowler; Marc van de Rijn; Kenneth M Attie

doi:10.1002/mus.27558

Back

Randomized Phase 2 Study of ACE-083, a Muscle-Promoting Agent, in Facioscapulohumeral Muscular Dystrophy

Journal article

Open access

Peer reviewed

Randomized Phase 2 Study of ACE-083, a Muscle-Promoting Agent, in Facioscapulohumeral Muscular Dystrophy

Jeffrey M Statland, Craig Campbell, Urvi Desai, Chafic Karam, Jordi Díaz-Manera, Jeffrey T Guptill, Lawrence Korngut, Angela Genge, Rabi N Tawil, Lauren Elman, …

Muscle & nerve, Vol.66(1), pp.50-62

04/15/2022

DOI: 10.1002/mus.27558

PMCID: PMC9321022

PMID: 35428982

Files and links (1)

url

https://doi.org/10.1002/mus.27558View

Published (Version of record) Open Access

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. This study evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD. Participants were ≥ 18 years old and had FSHD1/FSHD2. Part 1 was open-label, ascending dose, assessing safety and tolerability (primary objective). Part 2 was randomized, double-blind for 6 months, evaluating ACE-083240 mg/muscle versus placebo injected bilaterally every 3 weeks in the biceps brachii (BB) or tibialis anterior (TA) muscles, followed by 6 months' open-label. MRI measures included total muscle volume (TMV; primary objective), fat fraction (FF), and contractile muscle volume (CMV). Functional measures included 6-minute walk test, 10-m walk/run, and 4-stair climb (TA group), and performance of upper limb mid-level/elbow score (BB group). Strength, patient-reported outcomes (PROs), safety were also evaluated. Parts 1 and 2 enrolled 37 and 58 participants, respectively. Among 55 participants evaluable in Part 2, the least squares mean (90% CI, ANCOVA) treatment difference for TMV was 16.4% (9.8%, 23.0%) in the BB group (P < 0.0001) and 9.5% (3.2%, 15.9%) in the TA group (P = 0.01). CMV increased significantly in the BB and TA groups and FF decreased in the TA group. There were no consistent improvements in functional or PRO measures in either group. The most common adverse events were mild or moderate injection-site reactions. Significant increases in TMV with ACE-083 versus placebo did not result in consistent functional or PRO improvements with up to 12 months' treatment. This article is protected by copyright. All rights reserved.

facioscapulohumeral muscular dystrophy

FSHD

Randomized controlled trial

Details

Title: Subtitle: Randomized Phase 2 Study of ACE-083, a Muscle-Promoting Agent, in Facioscapulohumeral Muscular Dystrophy
Creators: Jeffrey M Statland - University of Kansas Medical Center
Craig Campbell - Western University
Urvi Desai - Carolinas MDA Care Center Atrium Health, Charlotte, North Carolina, USA
Chafic Karam - Oregon Health & Science University
Jordi Díaz-Manera - Newcastle University
Jeffrey T Guptill - Duke University School of Medicine
Lawrence Korngut - University of Calgary
Angela Genge - Montreal Neurological Institute, Montreal, QC, Canada
Rabi N Tawil - University of Rochester
Lauren Elman - University of Pennsylvania
Nanette C Joyce - University of California Davis Medical Center
Kathryn R Wagner - Kennedy Krieger Institute
Georgios Manousakis - University of Minnesota
Anthony A Amato - Brigham and Women's Hospital
Russell J Butterfield - University of Utah
Perry B Shieh - University of California Los Angeles, Los Angeles, CA, US
Matthew Wicklund - University of Colorado, Aurora, CO, US
Josep Gamez - Department of Medicine, GMA Clinic, European Reference Network on Rare Neuromuscular Diseases (ERN EURO-NMD) and Universitat Autònoma de Barcelona, Barcelona, Spain
Cynthia Bodkin - Indiana University
Alan Pestronk - Washington University School of Medicine, St. Louis, MO, US
Conrad C Weihl - Washington University School of Medicine, St. Louis, MO, US
Juan J Vilchez-Padilla - Instituto de Salud Carlos III
Nicholas E Johnson - Virginia Commonwealth University
Katherine D Mathews - University of Iowa
Barry Miller - Acceleron Pharma (United States)
Ashley Leneus - Acceleron Pharma (United States)
Marcie Fowler - Acceleron Pharma (United States)
Marc van de Rijn - Acceleron Pharma (United States)
Kenneth M Attie - Acceleron Pharma (United States)
Resource Type: Journal article
Publication Details: Muscle & nerve, Vol.66(1), pp.50-62
DOI: 10.1002/mus.27558
PMID: 35428982
PMCID: PMC9321022
NLM abbreviation: Muscle Nerve
eISSN: 1097-4598
Grant note: DOI: 10.13039/100014926, name: Acceleron
Language: English
Electronic publication date: 04/15/2022
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984242656802771

Metrics

27 Record Views

21 Times Cited - Web of Science