Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study
Mark A Agius, Gabriela Klodowska-Duda, Maciej Maciejowski, Andrzej Potemkowski, Jing Li, Kaushik Patra, Jacob Wesley, Soraya Madani, Gerard Barron, Eliezer Katz, Armando Flor, Mark A Agius, Gabriela Klodowska-Duda, Maciej Maciejowski, Andrzej Potemkowski, Jing Li, Kaushik Patra, Jacob Wesley, Soraya Madani, Gerard Barron, Eliezer Katz, Armando Flor
Abstract
Background: B cells may be involved in the pathophysiology of multiple sclerosis (MS). Inebilizumab (formerly MEDI-551) binds to and depletes CD19+ B cells.
Objectives: To assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of inebilizumab in adults with relapsing MS.
Methods: This phase 1 trial randomised 28 patients 3:1 (21, inebilizumab; 7, placebo) to inebilizumab (2 intravenous (IV) doses, days 1 and 15: 30, 100 or 600 mg; or single subcutaneous (SC) dose on day 1: 60 or 300 mg) or matching placebo, with follow-up until at least week 24 or return of CD19+ B-cell count to ⩾80 cells/µL.
Results: Complete B-cell depletion was observed across all doses. Infusion/injection (grade 1/2) reactions occurred in 6/15 patients receiving inebilizumab IV, 2/5 placebo IV and 1/6 inebilizumab SC. Serious adverse events occurred in three patients receiving inebilizumab: pyrexia, mixed-drug intoxication (unrelated to inebilizumab; resulted in death) and urinary tract infection. Mean number of cumulative new gadolinium-enhancing lesions over 24 weeks was 0.1 with inebilizumab versus 1.3 with placebo; mean numbers of new/newly enlarging T2 lesions were 0.4 and 2.4, respectively.
Conclusion: Inebilizumab had an acceptable safety profile in relapsing MS patients and showed a trend in reductions in new/newly enlarging and gadolinium-enhancing lesions.
Keywords: B cells; intravenous administration; pharmacodynamics; pharmacokinetics; subcutaneous administration.
Conflict of interest statement
Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: The University of California at Davis received funding, with M.A.A. as principal investigator, for the conduct of this study. M.A.A. has also served as a consultant for Novartis, Roche, Sanofi and Serono and has received research funding from Biogen, Celgene, Novartis, Roche and Sanofi. G.K.-D. has received research funding for the conduct of this study and has had travel, accommodation and/or investigator meeting expenses paid by MedImmune. M.M. has received lecture fees from Biogen, Novartis and Merck. A.P. received research funding for the conduct of this study and has served as a consultant and on an advisory board for MedImmune. J.L., K.P., J.W., S.M., G.B., E.K. and A.F. are employees of MedImmune and may own stock and/or stock options in AstraZeneca. M.A.A., G.K.-D., M.M. and A.P. received no honoraria or other form of financial support related to the development of this manuscript.
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