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

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 Participan...

Descripción completa

Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p9872
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9872
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321022
Access Level:acceso abierto
Palabra clave:facioscapulohumeral muscular dystrophy
FSHD
randomized
controlled trial
id ES_eeaf4fa5275f346c44cd2a40a3822cfd
oai_identifier_str oai:iibsantpau.fundanetsuite.com:p9872
network_acronym_str ES
network_name_str España
repository_id_str
spelling Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophyStatland, JMCampbell, CDesai, UKaram, CDiaz-Manera, JGuptill, JTKorngut, LGenge, ATawil, RNElman, LJoyce, NCWagner, KRManousakis, GAmato, AAButterfield, RJShieh, PBWicklund, MGamez, JBodkin, CPestronk, AWeihl, CCVilchez-Padilla, JJJohnson, NEMathews, KDMiller, BLeneus, AFowler, Mvan de Rijn, MAttie, KMfacioscapulohumeral muscular dystrophyFSHDrandomizedcontrolled trialIntroduction/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.WILEY2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9872https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321022MUSCLE & NERVEISSN: 0148639XISSNe: 10974598reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p98722026-06-14T12:41:47Z
dc.title.none.fl_str_mv Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
title Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
spellingShingle Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
Statland, JM
facioscapulohumeral muscular dystrophy
FSHD
randomized
controlled trial
title_short Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
title_full Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
title_fullStr Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
title_full_unstemmed Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
title_sort Randomized phase 2 study of ACE-083, a muscle-promoting agent, in facioscapulohumeral muscular dystrophy
dc.creator.none.fl_str_mv 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
author Statland, JM
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv facioscapulohumeral muscular dystrophy
FSHD
randomized
controlled trial
topic facioscapulohumeral muscular dystrophy
FSHD
randomized
controlled trial
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9872
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321022
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9872
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321022
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv MUSCLE & NERVE
ISSN: 0148639X
ISSNe: 10974598
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869423744097714176
score 15,812429

Similares en LA Referencia