Phase 2B randomized controlled trial of NP001 in amyotrophic lateral sclerosis: Pre-specified and post hoc analyses.
Muscle Nerve
; 66(1): 39-49, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35098554
ABSTRACT
INTRODUCTION/AIMS:
ALS is a heterogeneous disease that may be complicated or in part driven by inflammation. NP001, a regulator of macrophage activation, was associated with slowing disease progression in those with higher levels of the plasma inflammatory marker C-reactive protein (CRP) in phase 2A studies in ALS. Here, we evaluate the effects of NP001 in a phase 2B trial, and perform a post hoc analysis with combined data from the preceding phase 2A trial.METHODS:
The phase 2B trial enrolled 138 participants within 3 y of symptom onset and with plasma hs-CRP values >1.13 mg/L. They were randomized 11 to receive either placebo or NP001 for 6 mo. Change from baseline ALSFRS-R scores was the primary efficacy endpoint. Secondary endpoints included vital capacity (VC) change from baseline and percentage of participants showing no decline of ALSFRS-R score over 6 mo (non-progressor).RESULTS:
The phase 2B study did not show significant differences between placebo and active treatment with respect to change in ALSFRS-R scores, or VC. The drug was safe and well tolerated. A post hoc analysis identified a 40- to 65-y-old subset in which NP001-treated patients demonstrated slower declines in ALSFRS-R score by 36% and VC loss by 51% compared with placebo. A greater number of non-progressors were NP001-treated compared with placebo (p = .004).DISCUSSION:
Although the phase 2B trial failed to meet its primary endpoints, post hoc analyses identified a subgroup whose decline in ALSFRS-R and VC scores were significantly slower than placebo. Further studies will be required to validate these findings.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esclerose Lateral Amiotrófica
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Muscle Nerve
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos