TY - JOUR
T1 - A double-blind, placebo-controlled, single ascending-dose study of remyelinating antibody rHIgM22 in people with multiple sclerosis
AU - Eisen, Andrew
AU - Greenberg, Benjamin M.
AU - Bowen, James D.
AU - Arnold, Douglas L.
AU - Caggiano, Anthony O.
N1 - Publisher Copyright:
© The Author(s), 2017.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Objective: The objective of this paper is to assess, in individuals with clinically stable multiple sclerosis (MS), the safety, tolerability, pharmacokinetics (PK) and exploratory pharmacodynamics of the monoclonal recombinant human antibody IgM22 (rHIgM22). Methods: Seventy-two adults with stable MS were enrolled in a double-blind, randomized, placebo-controlled, single ascending-dose, Phase 1 trial examining rHIgM22 from 0.025 to 2.0 mg/kg. Assessments included MRI, MR spectroscopy, plasma PK, and changes in clinical status, laboratory values and adverse events for three months. The final cohort had additional clinical, ophthalmologic, CSF collection and exploratory biomarker evaluations. Participants were monitored for six months. Results: rHIgM22 was well tolerated with no clinically significant safety signals. Noncompartmental PK modeling demonstrated linear dose-proportionality both of Cmax and AUC0–Last. The steady-state apparent volume of distribution of approximately 58 ml/kg suggested primarily vascular compartmentalization. CSF:plasma rHIgM22 concentration increased from 0.003% on Day 2 for both 1.0 and 2.0 mg/kg to 0.056% and 0.586% for 1.0 and 2.0 mg/kg, respectively, on Day 29. No statistically significant treatment-related changes were observed in exploratory pharmacodynamic outcome measures included for the 21 participants of the extension cohort. Conclusions: Single doses of rHIgM22 were well tolerated and exhibited linear PK, and antibody was detected in the CSF.
AB - Objective: The objective of this paper is to assess, in individuals with clinically stable multiple sclerosis (MS), the safety, tolerability, pharmacokinetics (PK) and exploratory pharmacodynamics of the monoclonal recombinant human antibody IgM22 (rHIgM22). Methods: Seventy-two adults with stable MS were enrolled in a double-blind, randomized, placebo-controlled, single ascending-dose, Phase 1 trial examining rHIgM22 from 0.025 to 2.0 mg/kg. Assessments included MRI, MR spectroscopy, plasma PK, and changes in clinical status, laboratory values and adverse events for three months. The final cohort had additional clinical, ophthalmologic, CSF collection and exploratory biomarker evaluations. Participants were monitored for six months. Results: rHIgM22 was well tolerated with no clinically significant safety signals. Noncompartmental PK modeling demonstrated linear dose-proportionality both of Cmax and AUC0–Last. The steady-state apparent volume of distribution of approximately 58 ml/kg suggested primarily vascular compartmentalization. CSF:plasma rHIgM22 concentration increased from 0.003% on Day 2 for both 1.0 and 2.0 mg/kg to 0.056% and 0.586% for 1.0 and 2.0 mg/kg, respectively, on Day 29. No statistically significant treatment-related changes were observed in exploratory pharmacodynamic outcome measures included for the 21 participants of the extension cohort. Conclusions: Single doses of rHIgM22 were well tolerated and exhibited linear PK, and antibody was detected in the CSF.
KW - Clinical trial
KW - Demyelination
KW - Disease-modifying therapies
KW - Multiple sclerosis
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U2 - 10.1177/2055217317743097
DO - 10.1177/2055217317743097
M3 - Article
C2 - 29348926
AN - SCOPUS:85047078160
SN - 2055-2173
VL - 3
JO - Multiple Sclerosis Journal - Experimental, Translational and Clinical
JF - Multiple Sclerosis Journal - Experimental, Translational and Clinical
IS - 4
ER -