A double-blind, placebo-controlled, single-ascending-dose intravenous infusion study of rHIgM22 in subjects with multiple sclerosis immediately following a relapse

Benjamin M. Greenberg, James D. Bowen, Enrique Alvarez, Moses Rodriguez, Anthony O. Caggiano, Arthur E. Warrington, Ping Zhao, Andrew Eisen

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Recombinant human immunoglobulin M22 (rHIgM22) has promoted remyelination in animal models and was well tolerated in people with clinically stable multiple sclerosis. Objective: Safety/tolerability of a single rHIgM22 dose was investigated following an acute relapse and to determine whether this enhanced CNS/CSF concentrations. Methods: Adults (N = 27) with acute relapse were assigned to rHIgM22 (0.5 or 2.0 mg/kg) or placebo. Study included screening/steroid administration periods and 10 study visits over 6 months. rHIgM22 CSF concentrations were assessed on days 2 and 29. Pharmacokinetic and safety samples were taken for up to 60 days. Assessments included adverse events and other clinical measures. Brain magnetic resonance imaging was performed with/without gadolinium. Results: rHIgM22 CSF levels were consistent with dose-dependent concentration on both days 2 and 29. Infusion was generally well tolerated during an acute relapse. Immunogenicity was mild. Most adverse events did not appear to be dose dependent, were mild/moderate, and were events often associated with multiple sclerosis. Conclusion: Although limited by high variability and small sample size, the data suggest enhanced CNS uptake associated with a drop in CSF levels. This study demonstrated safety of an antibody directed to myelin and oligodendrocytes in the course of active demyelinating disease. Further research into rHIgM22 is warranted. ClinicalTrials.gov: NCT02398461 https://clinicaltrials.gov/ct2/show/study/NCT02398461?term=M22&draw=2&rank=8

Original languageEnglish (US)
JournalMultiple Sclerosis Journal - Experimental, Translational and Clinical
Volume8
Issue number2
DOIs
StatePublished - Apr 2022

Keywords

  • human immunoglobulin
  • immunogenicity
  • relapsing multiple sclerosis
  • remyelination
  • treatment

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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