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

• Published in: Multiple sclerosis Vol. 25; no. 2; pp. 235 - 245
• Main Authors: Agius, Mark A, Klodowska-Duda, Gabriela, Maciejowski, Maciej, Potemkowski, Andrzej, Li, Jing, Patra, Kaushik, Wesley, Jacob, Madani, Soraya, Barron, Gerard, Katz, Eliezer, Flor, Armando
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-02-2019; Sage Publications Ltd
• Subjects: Adult; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - pharmacokinetics; CD19 antigen; Dose-Response Relationship, Drug; Female; Fever; Gadolinium; Humans; Immunogenicity; Intoxication; Intravenous administration; Lymphocytes B; Male; Middle Aged; Monoclonal antibodies; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - pathology; Original Research Papers; Pharmacodynamics; Pharmacokinetics; Safety; Urinary tract; pharmacokinetics; intravenous administration; B cells; pharmacodynamics; subcutaneous administration
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458517740641

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.