Abstract

Objective: 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). Methods and materials: 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. Results: 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. Conclusions: 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 cytokine. Based< on this trial, further trials to explore the efficacy of anti-IL-21 were initiated.

Author Details

Authors

• Stanislav Ignatenko¹
• Birte K. Skrumsager²
• Ulrik Mouritzen²

Departments

• ¹ Charité Research Organisation GmbH, Berlin, Germany, and
• ² Novo Nordisk A/S, Copenhagen, Denmark

Address

Stanislav Ignatenko, MD, PhD
Charité Research Organisation GmbH
Charitéplatz 1, 10117 Berlin, Germany
Email: [email protected]

Citation