title: First-In-Human, Phase 1, Randomized, Dose-Escalation Trial with Recombinant Anti-IL-20 Monoclonal Antibody in Patients with Psoriasis.
abstract: BACKGROUND
  The current trial was a first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the recombinant monoclonal anti-interleukin-20 (IL-20) antibody, NNC0109-0012, which targets the inflammatory cytokine IL-20.
  
  
  METHODS
  In total, 48 patients aged 18 to 75 years with moderate to severe stable chronic plaque psoriasis with affected body surface area ≥15% and physician global assessment score ≥3 were enrolled in this randomized, double-blind, multicenter, placebo-controlled, phase 1 dose-escalation trial. Patients were randomized within each single dose cohort (0.01, 0.05, 0.2, 0.6, 1.5, or 3.0 mg/kg) or multiple dose cohort (0.05, 0.2, 0.5, 1.0, or 2.0 mg/kg; 1 dose every other week for 7 weeks) of NNC0109-0012 or placebo in a 3:1 ratio. In the expansion phase, 7 patients were randomized to weekly doses of 2.0 mg/kg NNC0109-0012 or placebo for 7 weeks. The primary objective, safety and tolerability, was assessed by evaluating adverse events (AEs). Additional endpoints included pharmacokinetics, pharmacodynamics, and clinical response (assessed using the Psoriasis Area and Severity Index [PASI] score).
  
  
  RESULTS
  AEs were reported in 85% of patients (n = 40) in the initial study phases (NNC0109-0012, 83%; placebo, 92%) and in 4 of 7 patients in the multiple-dose expansion phase. One serious AE was reported but was judged not to be causally related to NNC0109-0012. No dose-limiting toxicities were reported. NNC0109-0012 pharmacokinetics was similar to other monoclonal antibodies, with an average half-life of approximately 3 weeks. There was a dose-proportional increase in area under the curve and maximum concentration after single dosing. No substantial changes in pharmacodynamic parameters were observed. The expansion phase was terminated early due to apparent lack of PASI improvement.
  
  
  CONCLUSIONS
  Single and multiple doses of NNC0109-0012, ranging from 0.05 to 3.0 mg/kg, were well tolerated in patients with psoriasis and exhibited pharmacokinetics similar to that of other monoclonal antibodies.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01261767.
authors.affiliation: Department of Dermatology, Tufts Medical Center, Boston, MA, United States of America; Department of Dermatology, Tufts University School of Medicine, Boston, MA, United States of America.
authors.forename: Alice B
authors.initials: AB
authors.lastname: Gottlieb
authors.affiliation: The Rockefeller University, New York, NY, United States of America.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Mia
authors.initials: M
authors.lastname: Sandberg Lundblad
authors.affiliation: Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Marie
authors.initials: M
authors.lastname: Göthberg
authors.affiliation: Medical-Science, Inflammation, Novo Nordisk Inc., Princeton, NJ, United States of America.
authors.forename: Brett E
authors.initials: BE
authors.lastname: Skolnick
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000080908:Broadly Neutralizing Antibodies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; D007378:Interleukins; D011994:Recombinant Proteins; C000600094:Fletikumab; C422042:interleukin 20