title: Safety, PK, and PD of recombinant anti-interleukin-21 monoclonal antibody in a first-in-human trial.
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
  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.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Ignatenko
authors.forename: Birte K
authors.initials: BK
authors.lastname: Skrumsager
authors.forename: Ulrik
authors.initials: U
authors.lastname: Mouritzen
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects; D000098546:Interleukin-21
chemical_list: D000911:Antibodies, Monoclonal; D007378:Interleukins; D011994:Recombinant Proteins; D000098546:Interleukin-21