TY - JOUR
T1 - A double-blind, placebo-controlled, single-ascending-dose intravenous infusion study of rHIgM22 in subjects with multiple sclerosis immediately following a relapse
AU - Greenberg, Benjamin M.
AU - Bowen, James D.
AU - Alvarez, Enrique
AU - Rodriguez, Moses
AU - Caggiano, Anthony O.
AU - Warrington, Arthur E.
AU - Zhao, Ping
AU - Eisen, Andrew
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Acorda Therapeutics, Inc, (grant number N/A).
Funding Information:
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Xxxxxxx. B.M. Greenberg has received consulting fees from Alexion, Novartis, EMD Serono, Viela Bio, Genentech/Roche, Greenwich Biosciences, Axon Advisors, Rubin Anders, ABCAM, Signant, IQVIA, Sandoz, Druggability Technologies, Genzyme, Immunovant, and PRIME Education. He has received grant funding from PCORI, NIH, NMSS, The Siegel Rare Neuroimmune Association, Clene Nanomedicine, and the Guthy Jackson Charitable Foundation for NMO. He serves as an unpaid member of the board of the Siegel Rare Neuroimmune Association. He receives royalties from UpToDate. J.D. Bowen has received compensation for activities such as advisory boards, lectures, and consultancy with the following companies and organizations: AbbVie, Alkermes, Biogen IDEC, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, Genzyme, Novartis, and Roche. E. Alvarez has received compensation for activities such as advisory boards, lectures, and consultancy with the following companies and organizations: Actelion/Janssen, Alexion, Bayer, Biogen, Celgene/BMS, EMD Serono/Merck, Genentech/Roche, Genzyme, Novartis, and TG Therapeutics. He has also received research support from Biogen, Genentech/Roche, Novartis, TG Therapeutics, Patient-Centered Outcomes Research Initiative, National Multiple Sclerosis Society, National Institutes of Health, and Rocky Mountain MS Center. M.R. Rodriguez and A.E.W. Warrington: The Mayo Clinic owns patents and has licensed rHIgM22 to Acorda Therapeutics. If the antibody proves to be effective, then royalties may be received. A. Caggiano, Ping Zhao and A. Eisen were employees of Acorda Therapeutics at the time of the study, and A. Caggiano and A. Eisen own stock in Acorda.
Publisher Copyright:
© The Author(s), 2022.
PY - 2022/4
Y1 - 2022/4
N2 - 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
AB - 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
KW - human immunoglobulin
KW - immunogenicity
KW - relapsing multiple sclerosis
KW - remyelination
KW - treatment
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U2 - 10.1177/20552173221091475
DO - 10.1177/20552173221091475
M3 - Article
C2 - 35496758
AN - SCOPUS:85129187196
VL - 8
JO - Multiple Sclerosis Journal - Experimental, Translational and Clinical
JF - Multiple Sclerosis Journal - Experimental, Translational and Clinical
SN - 2055-2173
IS - 2
ER -