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 - 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
SN - 2055-2173
VL - 8
JO - Multiple Sclerosis Journal - Experimental, Translational and Clinical
JF - Multiple Sclerosis Journal - Experimental, Translational and Clinical
IS - 2
ER -