Safety, PK, and PD of recombinant anti-interleukin-21 monoclonal antibody in a first-in-human trial

International Journal of Clinical Pharmacology and Therapeutics
Stanislav IgnatenkoUlrik Mouritzen

Abstract

This first-in-human, randomized, double-blind, placebo-controlled trial assessed the safety of NNC0114-0005, a human recombinant anti interleukin (IL)-21 monoclonal antibody, for the treatment of rheumatoid arthritis (RA). Healthy male subjects (HS (n = 44)) and patients with active RA treated with methotrexate (n = 20) were randomized 3 : 1 to single IV or SC doses of NNC0114-0005 (0.0025 - 25 mg/kg) or placebo. Safety endpoints, pharmacokinetics, and pharmacodynamics were assessed over 12 weeks. All study participants were analyzed. 37 AEs were reported in 21 NNC0114-0005-treated participants (44%) and 18 AEs in 10 placebo-treated participants (63%), with no dose-dependency. The most common AEs were headache and nasopharyngitis; there were no injection-site reactions Linear pharmacokinetics of NNC0114-0005 were indicated (mean terminal half-life, 2 - 3 weeks). Dose-dependent total IL-21 (free IL-21 and IL-21‒NNC0114-0005 complexes) accumulation was observed. Preliminary signs of reduced RA activity were observed with 25 mg/kg NNC0114-0005. Single doses of NNC0114-0005 (≤ 25 mg/kg IV; ≤ 4 mg/kg SC) were well tolerated in HS and patients with RA. Accumulation of IL-21-containing complexes suggests neutralization of the target c...Continue Reading

Citations

Jan 17, 2017·Clinical & Translational Immunology·Wilhelmina Maria Cornelia TimmermansMenno Cornelis van Zelm
Mar 8, 2018·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Y LiuZ Liu
Apr 11, 2019·Nature Reviews. Rheumatology·Samuel J S RubinWilliam H Robinson
Mar 5, 2021·The Lancet. Diabetes & Endocrinology·Matthias von HerrathUNKNOWN Anti-IL-21–liraglutide Study Group investigators and contributors
Feb 19, 2019·Journal of Autoimmunity·Di LongQianjin Lu
Apr 6, 2021·Journal of Immunology Research·Kailei Guo, Xiaomin Zhang
Apr 22, 2021·Cellular and Molecular Life Sciences : CMLS·Jian LuShengjun Wang
Apr 29, 2021·Transplantation·Kevin LouisDiana Metes

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