Phase 2B randomized controlled trial of NP001 in amyotrophic lateral sclerosis: Pre-specified and post hoc analyses.

Journal Article (Journal Article)

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 1:1 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.

Full Text

Duke Authors

Cited Authors

  • Miller, RG; Zhang, R; Bracci, PM; Azhir, A; Barohn, R; Bedlack, R; Benatar, M; Berry, JD; Cudkowicz, M; Kasarskis, EJ; Mitsumoto, H; Manousakis, G; Walk, D; Oskarsson, B; Shefner, J; McGrath, MS

Published Date

  • July 2022

Published In

Volume / Issue

  • 66 / 1

Start / End Page

  • 39 - 49

PubMed ID

  • 35098554

Pubmed Central ID

  • PMC9327716

Electronic International Standard Serial Number (EISSN)

  • 1097-4598

Digital Object Identifier (DOI)

  • 10.1002/mus.27511


  • eng

Conference Location

  • United States