Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
Por:
Statland, JM, Campbell, C, Desai, U, Karam, C, Diaz-Manera, J, Guptill, JT, Korngut, L, Genge, A, Tawil, RN, Elman, L, Joyce, NC, Wagner, KR, Manousakis, G, Amato, AA, Butterfield, RJ, Shieh, PB, Wicklund, M, Gamez, J, Bodkin, C, Pestronk, A, Weihl, CC, Vilchez-Padilla, JJ, Johnson, NE, Mathews, KD, Miller, B, Leneus, A, Fowler, M, van de Rijn, M, Attie, KM
Publicada:
1 jul 2022
Ahead of Print:
1 may 2022
Resumen:
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.
Filiaciones:
Statland, JM:
Univ Kansas, Dept Neurol, Med Ctr, Kansas City, KS 66160 USA
Campbell, C:
Univ Western Ontario, Dept Pediat & Clin Neurol Sci, London, ON, Canada
Desai, U:
Atrium Hlth, Carolinas MDA Care Ctr, Charlotte, NC USA
Karam, C:
Oregon Hlth & Sci Univ, Neuromuscular Div, Portland, OR 97201 USA
Diaz-Manera, J:
Hosp Santa Creu & Sant Pau, Neuromuscular Dis Unit, Neurol Dept, Barcelona, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras, Madrid, Spain
Newcastle Univ, John Walton Muscular Dystrophy Res Ctr, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England
Guptill, JT:
Duke Univ, Dept Neurol, Sch Med, Durham, NC USA
Korngut, L:
Univ Calgary, Calgary, AB, Canada
Genge, A:
Montreal Neurol Inst, Montreal, PQ, Canada
Tawil, RN:
Univ Rochester, Sch Med, Rochester, NY USA
Elman, L:
Univ Penn, Philadelphia, PA 19104 USA
Joyce, NC:
Univ Calif Davis, Med Ctr, Davis, CA 95616 USA
Wagner, KR:
Johns Hopkins Sch Med, Kennedy Krieger Inst, Baltimore, MD USA
Manousakis, G:
Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA
Amato, AA:
Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA
Butterfield, RJ:
Univ Utah, Dept Neurol, Salt Lake City, UT USA
Univ Utah, Dept Pediat, Salt Lake City, UT USA
Shieh, PB:
Univ Calif Los Angeles, Los Angeles, CA USA
Wicklund, M:
Univ Colorado, Aurora, CO USA
Gamez, J:
European Reference Network Rare Neuromuscular Dis, Dept Med, GMA Clin, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Bodkin, C:
Indiana Univ Sch Med, Indianapolis, IN 46202 USA
Pestronk, A:
Washington Univ, Sch Med, St Louis, MO USA
Weihl, CC:
Washington Univ, Sch Med, St Louis, MO USA
Vilchez-Padilla, JJ:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras, Madrid, Spain
Hosp UIP La Fe, Neuromuscular Reference Ctr, Valencia, Spain
Johnson, NE:
Virginia Commonwealth Univ, Richmond, VA USA
Mathews, KD:
Univ Iowa, Carver Coll Med, Iowa City, IA USA
Miller, B:
Acceleron Pharma, Cambridge, MA USA
Leneus, A:
Acceleron Pharma, Cambridge, MA USA
Fowler, M:
Acceleron Pharma, Cambridge, MA USA
van de Rijn, M:
Acceleron Pharma, Cambridge, MA USA
Attie, KM:
Acceleron Pharma, Cambridge, MA USA
Green Published, Hybrid Gold, Green
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