Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
Statland, J.M. (University of Kansas Medical Center)
Campbell, C. (University of Western Ontario)
Desai, Urvi (Carolinas MDA Care Center)
Karam, C. (Oregon Health & Science University)
Diaz-Manera, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Guptill, J.T. (Duke University School of Medicine)
Korngut, L. (University of Calgary)
Genge, A. (Montreal Neurological Institute)
Tawil, R.N. (University of Rochester School of Medicine)
Elman, Lauren B (University of Pennsylvania)
Joyce, N.C. (University of California Davis Medical Center)
Wagner, K.R. (Kennedy Krieger Institute)
Manousakis, G. (University of Minnesota)
Amato, A.A. (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Butterfield, R.J. (University of Utah)
Shieh, P.B. (University of California Los Angeles)
Wicklund, M. (University of Colorado)
Gamez, Josep (Universitat Autònoma de Barcelona. Departament de Medicina)
Bodkin, C. (Indiana University School of Medicine)
Pestronk, A. (Washington University School of Medicine)
Weihl, C.C. (Washington University School of Medicine)
Vilchez-Padilla, J.J. (Hospital UIP La Fe. Neuromuscular Reference Centre)
Johnson, N.E. (Virginia Commonwealth University)
Mathews, K.D. (University of Iowa)
Miller, B. (Acceleron Pharma)
Leneus, A. (Acceleron Pharma)
Fowler, M. (Acceleron Pharma)
van de Rijn, M. (Acceleron Pharma)
Attie, K.M. (Acceleron Pharma)

Data:	2022
Resum:	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. 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. 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. 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.
Ajuts:	Ministerio de Economía y Competitividad PI16/01673 Instituto de Salud Carlos III PI19/00593
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Controlled trial ; Facioscapulohumeral muscular dystrophy ; FSHD ; Randomized
Publicat a:	Muscle & nerve, Vol. 66 Núm. 1 (july 2022) , p. 50-62, ISSN 1097-4598

DOI: 10.1002/mus.27558
PMID: 35428982

13 p, 2.9 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
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