Randomized phase 2 trial of NP001-a novel immune regulator: Safety and early efficacy in ALS

Robert G. Miller, Gilbert Block, Jonathan S. Katz, Richard J. Barohn, Vidhya Gopalakrishnan, Merit Cudkowicz, Jane R. Zhang, Michael S. McGrath, Elizabeth Ludington, Stanley H. Appel, Ari Azhir

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Objective: To assess the safety, tolerability, and preliminary efficacy of NP001, a novel immune regulator of inflammatory monocytes/macrophages, for slowing progression of amyotrophic lateral sclerosis (ALS). Methods: This was a phase 2 randomized, double-blind, placebo-controlled trial of NP001 in 136 patients with ALS of,3 years' duration and forced vital capacity >70%. Participants received NP001 2 mg/kg, NP001 1 mg/kg, or placebo for 6 months. Safety, tolerability, and inflammatory biomarkers were assessed throughout the study. Preliminary efficacy was evaluated using the ALS Functional Rating Scale-Revised (ALSFRS-R) slope and change from baseline, with and without matched historical placebo controls, after 6 months of treatment. A post hoc analysis of the percentage of patients ("responders") whose ALSFRS-R did not change from baseline was also conducted. Results: NP001 was generally safe and well-tolerated, except for infusion site pain and dizziness. No significant slowing of decline in the primary or secondary measures was observed. However, slowing of progression was observed in the high-dose group in patients with greater inflammation (wide range C-reactive protein). Moreover, NP001 may have dose dependently halted symptom progression in a subset of patients. More than 2 times as many patients on high-dose NP001 (25%) did not progress during 6 months of treatment compared with those on placebo (11%). Most "responders" had an elevated biomarker of inflammation, interleukin-18, and were positive for lipopolysaccharide at baseline, which decreased after treatment with NP001. Conclusion: The arresting of progression of ALS symptoms by NP001 in a subset of patients with marked neuroinflammation, as observed here, will represent a novel therapeutic approach for patients with ALS, if confirmed. Classification of evidence: This study provides Class I evidence that for patients with ALS, NP001 is safe and did not significantly slow progression of the disease (difference in slope of the ALSFRS-R/month 0.12 favoring NP001, p 5 0.55). The study lacks the precision to exclude an important effect of NP001.

Original languageEnglish (US)
Pages (from-to)e100
JournalNeurology: Neuroimmunology and NeuroInflammation
Issue number3
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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