Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study.
Mult Scler
; 28(3): 429-440, 2022 Mar.
Article
en En
| MEDLINE
| ID: mdl-34240656
ABSTRACT
BACKGROUND:
The envelope protein of human endogenous retrovirus W (HERV-W-Env) is expressed by macrophages and microglia, mediating axonal damage in chronic active MS lesions. OBJECTIVE ANDMETHODS:
This phase 2, double-blind, 48-week trial in relapsing-remitting MS with 48-week extension phase assessed the efficacy and safety of temelimab; a monoclonal antibody neutralizing HERV-W-Env. The primary endpoint was the reduction of cumulative gadolinium-enhancing T1-lesions in brain magnetic resonance imaging (MRI) scans at week 24. Additional endpoints included numbers of T2 and T1-hypointense lesions, magnetization transfer ratio, and brain atrophy. In total, 270 participants were randomized to receive monthly intravenous temelimab (6, 12, or 18 mg/kg) or placebo for 24 weeks; at week 24 placebo-treated participants were re-randomized to treatment groups.RESULTS:
The primary endpoint was not met. At week 48, participants treated with 18 mg/kg temelimab had fewer new T1-hypointense lesions (p = 0.014) and showed consistent, however statistically non-significant, reductions in brain atrophy and magnetization transfer ratio decrease, as compared with the placebo/comparator group. These latter two trends were sustained over 96 weeks. No safety issues emerged.CONCLUSION:
Temelimab failed to show an effect on features of acute inflammation but demonstrated preliminary radiological signs of possible anti-neurodegenerative effects. Current data support the development of temelimab for progressive MS. TRIAL REGISTRATION CHANGE-MS ClinicalTrials.gov NCT02782858, EudraCT 2015-004059-29; ANGEL-MS ClinicalTrials.gov NCT03239860, EudraCT 2016-004935-18.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Esclerosis Múltiple Recurrente-Remitente
/
Anticuerpos Monoclonales Humanizados
/
Esclerosis Múltiple
Tipo de estudio:
Clinical_trials
Límite:
Humans
Idioma:
En
Revista:
Mult Scler
Asunto de la revista:
NEUROLOGIA
Año:
2022
Tipo del documento:
Article