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FRI0196 NNC0109-0012 (anti-IL-20 MAB), well tolerated in healthy subjects and patients with rheumatoid arthritis
  1. N. Al Kotbi1,
  2. L. Jensen2,
  3. L.B. Graff3
  1. 1Early Development Services, PRA International, Zuidlaren, Netherlands
  2. 2Clinical Pharmacology
  3. 3Medical and Science, Inflammation, Novo Nordisk A/S, Søborg, Denmark

Abstract

Background In patients with rheumatoid arthritis (RA), interleukin 20 (IL-20) is present in detectable amounts in synovial fluid, and IL-20 is thought to play a role in the pathophysiology of RA as a proinflammatory cytokine. NNC0109-0012 is a novel human monoclonal IgG4 antibody which binds to and neutralises IL-20. Currently, NNC0109-0012 is being developed for the treatment of patients with RA.

Objectives The primary objective of this phase 1 trial was to assess the safety and tolerability of single doses of NNC0109-0012 administered subcutaneously to healthy subjects (HS) and patients with RA. The secondary objectives were to assess the pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity.

Methods The trial was a single-centre, double-blind, placebo-controlled, single-dose, dose-escalation trial. Subjects, aged 18 to 75 years, were randomised 3:1. A total of 20 HS received one of the following 5 single doses of NNC0109-0012: 0.05, 0.2, 0.6, 1.5 or 3.0 mg/kg or placebo; 12 patients with RA received one of the following 3 single doses of NNC0109-0012: 0.05, 0.6 or 3.0 mg/kg or placebo. All doses were administered subcutaneously in the abdominal wall. Additional inclusion criteria for subjects with RA were: diagnosis of RA according to the American College of Rheumatology (ACR1987 classification) at least 3 months prior to randomisation with active disease characterised by a DAS28 >3.2, and on stable methotrexate treatment (≤25 mg/week) for at least 4 weeks and with concomitant folic acid intake of doses at 1 mg/day or 5 mg/week. Key safety parameters included adverse events (AEs), changes in vital signs, injection-site reactions, acute-phase cytokines, lymphocyte subsets and analysis of antibodies against NNC0109-0012. PK and PD markers (including CRP, ESR, RF and proteins biomarkers) were assessed.

Results A total of 93 AEs were reported for 24 of 32 (75%) subjects. Overall, there were equal proportions of subjects with an AE in the NNC0109-0012 and placebo groups (75%) and no difference in the proportion of AEs in HS and patients with RA receiving NNC0109-0012 (73% and 77% respectively). A total of 38 AEs were evaluated as probably/possibly related to trial product: NNC0109-0012: 28 events, 11 subjects (46%), placebo: 10 events, 5 subjects (63%). No deaths or AEs leading to withdrawal were reported. No subjects developed antibodies against NNC0109-0012 up to 106 days post-dosing. Linear PK in the dose range 0.05-3.00 mg/kg was indicated in both HS and patients with RA. No statistically significant difference was observed in the single-dose PK properties of NNC0109-0012 between HS and patients with RA. The mean terminal t1/2 ranged from 30–35 days in HS and from 25–28 days in patients with RA. No clinically relevant changes were observed in acute-phase cytokines, lymphocyte subsets, protein biomarkers, clinical laboratory parameters or vital signs.

Conclusions NNC0109-0012 appeared safe and well tolerated in HS and patients with active RA at single doses of 0.05–3.0 mg/kg. No antibodies against NNC0109-0012 were detected and linear PK was observed for NNC0109-0012.

Disclosure of Interest N. Al Kotbi: None Declared, L. Jensen Employee of: Novo Nordisk A/S, L. Graff Employee of: Novo Nordisk A/S at the time of trial conduct

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