2. Academic Validation
  3. Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy

Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy

  • Muscle Nerve. 2022 Jul;66(1):50-62. doi: 10.1002/mus.27558.
Jeffrey M Statland 1,  Craig Campbell 2,  Urvi Desai 3,  Chafic Karam 4,  Jordi Díaz-Manera 5 6 7,  Jeffrey T Guptill 8,  Lawrence Korngut 9,  Angela Genge 10,  Rabi N Tawil 11,  Lauren Elman 12,  Nanette C Joyce 13,  Kathryn R Wagner 14,  Georgios Manousakis 15,  Anthony A Amato 16,  Russell J Butterfield 17,  Perry B Shieh 18,  Matthew Wicklund 19,  Josep Gamez 20,  Cynthia Bodkin 21,  Alan Pestronk 22,  Conrad C Weihl 22,  Juan J Vilchez-Padilla 23 6,  Nicholas E Johnson 24,  Katherine D Mathews 25,  Barry Miller 26,  Ashley Leneus 26,  Marcie Fowler 26,  Marc van de Rijn 26,  Kenneth M Attie 26
Affiliations

Affiliations

  • 1 Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA.
  • 2 Department of Pediatrics and Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada.
  • 3 Carolinas MDA Care Center, Atrium Health, Charlotte, North Carolina, USA.
  • 4 Neuromuscular Division, Oregon Health & Science University, Portland, Oregon, USA.
  • 5 Neuromuscular Diseases Unit, Neurology Department, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
  • 6 Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
  • 7 John Walton Muscular Dystrophy Research Centre, Newcastle University Translational and Clinical Research Institute, Newcastle, UK.
  • 8 Department of Neurology, Duke University School of Medicine, Durham, North Carolina, USA.
  • 9 University of Calgary, Calgary, Alberta, Canada.
  • 10 Montreal Neurological Institute, Montreal, Quebec, Canada.
  • 11 University of Rochester School of Medicine, Rochester, New York, USA.
  • 12 University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • 13 University of California Davis Medical Center, Davis, California, USA.
  • 14 Johns Hopkins School of Medicine, Kennedy Krieger Institute, Baltimore, Maryland, USA.
  • 15 Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA.
  • 16 Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • 17 Departments of Neurology and Pediatrics, University of Utah, Salt Lake City, Utah, USA.
  • 18 University of California Los Angeles, Los Angeles, California, USA.
  • 19 University of Colorado, Aurora, Colorado, USA.
  • 20 Department of Medicine, GMA Clinic, European Reference Network on Rare Neuromuscular Diseases (ERN EURO-NMD) and Universitat Autònoma de Barcelona, Barcelona, Spain.
  • 21 Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • 22 Washington University School of Medicine, St. Louis, Missouri, USA.
  • 23 Hospital UIP La Fe, Neuromuscular Reference Centre, Valencia, Spain.
  • 24 Virginia Commonwealth University, Richmond, Virginia, USA.
  • 25 Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
  • 26 Acceleron Pharma, Cambridge, Massachusetts, USA.
PMID: 35428982 DOI: 10.1002/mus.27558
Abstract

Introduction/aims: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD.

Methods: Participants were at least 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 vs placebo injected bilaterally every 3 weeks in the biceps brachii (BB) or tibialis anterior (TA) muscles, followed by 6 months of open label. Magnetic resonance imaging measures included total muscle volume (TMV; primary objective), fat fraction (FF), and contractile muscle volume (CMV). Functional measures included 6-minute walk test, 10-meter walk/run, and 4-stair climb (TA group), and performance of upper limb midlevel/elbow score (BB group). Strength, patient-reported outcomes (PROs), and safety were also evaluated.

Results: Parts 1 and 2 enrolled 37 and 58 participants, respectively. Among 55 participants evaluable in Part 2, the least-squares mean (90% confidence interval, analysis of covariance) treatment difference for TMV was 16.4% (9.8%-23.0%) in the BB group (P < .0001) and 9.5% (3.2%-15.9%) in the TA group (P = .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.

Discussion: Significant increases in TMV with ACE-083 vs placebo did not result in consistent functional or PRO improvements with up to 12 months of treatment.

Keywords

FSHD; controlled trial; facioscapulohumeral muscular dystrophy; randomized.

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