An open-label pilot study of losmapimod to evaluate the safety, tolerability, and changes in biomarker and clinical outcome assessments in participants with facioscapulohumeral muscular dystrophy type 1.
J Neurol Sci
; 462: 123096, 2024 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-38959779
ABSTRACT
INTRODUCTION:
Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disease caused by aberrant DUX4 expression, leading to progressive muscle weakness. No effective pharmaceutical treatment is available. Losmapimod, a small molecule selective inhibitor of p38 α/ß MAPK, showed promising results in a phase 1 trial for the treatment of FSHD, prompting additional studies. We report the findings of an open-label phase 2 trial (NCT04004000) investigating the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of losmapimod in participants with FSHD1.METHODS:
This study was conducted at a single site in the Netherlands from August 2019 to March 2021, with an optional, ongoing open-label extension. Participants aged 18 to 65 years with FSHD1 took 15 mg of losmapimod twice daily for 52 weeks. Primary endpoints were measures of losmapimod safety and tolerability. Secondary endpoints were assessments of losmapimod pharmacokinetics and pharmacodynamics.RESULTS:
Fourteen participants were enrolled. No deaths, serious treatment-emergent adverse events (TEAEs), or discontinuations due to TEAEs were reported. Losmapimod achieved blood concentrations and target engagements that were previously associated with decreased DUX4 expression in vitro. Clinical outcome measures showed a trend toward stabilization or improvement.CONCLUSIONS:
Losmapimod was well tolerated and may be a promising new treatment for FSHD; a larger phase 3 study is ongoing.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biomarcadores
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Distrofia Muscular Facioescapulohumeral
Límite:
Adolescent
/
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neurol Sci
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos