Background NNC0109-0012 (anti-IL-20 mAb) is a novel human monoclonal IgG4 antibody which binds to IL-20 and neutralises its activity. The primary endpoint in this multicentre, randomised, double-blind, placebo-controlled, parallel group trial (DAS28 response at Week 12) was achieved, as reported elsewhere.
Objectives To assess the effect of NNC0109-0012 on patient-reported outcomes, a secondary endpoint in this phase 2a proof-of-principle trial.
Methods 67 patients with active RA and inadequate responses to MTX were randomised to 12 once-weekly doses of 3mg/kg NNC0109-0012 (n=45) or placebo (n=22) and stable background MTX, and then followed for an additional 13 weeks. Of the 67 randomised patients 43 were Rheumatoid Factor [RF]- and anti-citrullinated peptide antibody [ACPA]-positive. Physical function was assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI). The level of pain and global disease activity were recorded by the patients on a 10 cm Visual Analogue Scale (VAS). All patient-reported outcomes were assessed weekly from baseline to week 12, and an additional 3 times in the 13 week follow-up period. A mixed-effects model repeated measures was fitted to the change from baseline for each of the patient-reported outcomes including treatment; time and interaction between treatment and time as fixed factors; baseline score and interaction between time and baseline score as continuous covariates and subject as random effect.
Results In RF- and ACPA-positive patients all patient-reported outcomes were significantly improved. Physical function was significantly improved after 12 and 25 weeks (-0.45, p=0.047; -0.47, p=0.022, respectively). After 12 and 25 weeks, NNC0109-0012 versus placebo significantly reduced pain (-3.0 cm, p<0.001; -2.9 cm, p<0.001, respectively) and global disease activity (-2.8 cm, p=0.002; -2.8 cm, p<0.001, respectively). For both pain and global disease activity the effects in the RF- and ACPA-positive patients were up to 2 fold larger versus placebo than was observed for the Full Analysis Set. For the Full Analysis Set, physical function was not significantly improved for NNC0109-0012 versus placebo after end of treatment at 12 weeks (-0.26, p=0.130). Pain was significantly reduced for NNC0109-0012 versus placebo with a mean difference of -1.5 cm (p=0.034) after 12 weeks and -1.3 cm (p=0.046) at week 25. Global disease activity was significantly lower for patients treated with NNC0109-0012 versus placebo with a mean difference of -1.7 cm (p=0.018) after 12 weeks, and was maintained through the follow-up period with a mean difference of -1.4 cm (p=0.031) at week 25.
Conclusions 12-weeks treatment with 3 mg/kg NNC0109-0012 effectively improved physical function, pain and global disease activity in RF- and ACPA-positive patients with RA on stable MTX. These improvements were clinically relevant and sustained when measured at the end of the 13 weeks follow-up.
Disclosure of Interest L. Senolt: None Declared, B. Hansen Employee of: Novo Nordisk, M. Strandberg-Larsen Employee of: Novo Nordisk, E. Dokoupilova: None Declared