Background Interleukin 20 (IL-20) and its receptors are present in rheumatoid arthritis (RA) synovial tissue and IL-20 is thought to play a role in the pathophysiology of RA as a proinflammatory cytokine. NNC0109-0012 (Anti-IL-20) is a novel human monoclonal IgG4 antibody which targets 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 one dose per week for seven consecutive weekly doses of NNC0109-0012 in patients with RA, administered subcutaneously at two dose levels (1.0 or 3.0 mg/kg), compared to placebo. Secondary objectives included pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and clinical signs of efficacy.
Methods A total of 16 patients with RA (1987 ACR classification) were enrolled in a multi-centre, randomised, double-blind, placebo-controlled, multiple-dose, dose-escalation trial. Patients were 18 to 75 years and had active RA (DAS28-CRP ≥3.2) on stable methotrexate treatment (≤25 mg/week). Patients could also be receiving oral corticosteroids (≤10 mg/day), NSAIDs (not Cox-2 inhibitors), acetaminophen and/or opioids. Randomisation was in a 3:1 ratio (6 NNC0109-0012 and 2 placebo subjects per dose level). Key safety parameters included adverse events (AEs), injection-site reactions and detection of antibodies against NNC0109-0012. PK and PD parameters were assessed. Efficacy evaluations included DAS28 (ESR and hs-CRP), ACR20, 50 and 70.
Results In total, 32 AEs were reported for 9/16 (56%) patients. Most common AEs were injection-site reactions (50%), 7 of which were from a single patient on active treatment (3.0 mg/kg). There were 11 possibly/probably related AEs in the 3.0 mg/kg group. One serious AE (RA flare-up, unlikely related to drug) occurred 69 days after last dose of active drug.
No deaths were reported and no patient withdrew due to an AE. No clinically relevant changes were observed in laboratory parameters or vital signs. No antibodies against NNC0109-0012 were detected. PK data shows linear dose proportionality for both dose levels with t1/2 of 17-19 days. No significant changes were observed in hs-CRP or ESR. DAS28 (hs-CRP) significantly improved in patients treated with 3.0 mg/kg NNC0109-0012 compared with placebo (p=0.038). DAS28 (ESR) also improved, but not significantly for patients treated with NNC0109-0012 as compared with placebo. A higher proportion of patients treated with NNC0109-0012 achieved ACR20 and ACR50 responses than patients treated with placebo (not statistically significant). No patients obtained ACR70 response. The greatest and earliest onset of improvements in DAS28 (ESR) and ACR-N were observed in patients treated with 3 mg/kg NNC0109-0012.
Conclusions NNC0109-0012 was well tolerated in patients with RA and no safety issues were identified in this trial. Doses of 1.0 and 3.0 mg/kg NNC0109-0012 demonstrated linear PK. The trial provided indications of reduced disease activity in patients with RA treated with NNC0109-0012.
Disclosure of Interest P. Leszczyński: None Declared, M. Eshof Employee of: Novo Nordisk A/S, H. Stegmann Employee of: Novo Nordisk A/S, N. Hundahl Møller Employee of: Novo Nordisk A/S, L. Graff Employee of: Novo Nordisk A/S at the time of trial conduct