EFFICACY, SAFETY, PHARMACOKINETICS AND IMMUNOGENICITY OF REPEATED DOSING OF GSK3858279 IN PATIENTS WITH KNEE OSTEOARTHRITIS: A PHASE I, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY
Authors: Nijjar J. et al.
In this randomized, double-blind placebo-controlled phase I study from UK an anti-CCL17 monoclonal antibody (GSK3858279) was tested in patients with knee osteoarthritis. The chemokine CCL17 mediates inflammatory pain and blocking CCL17 reduces pain and joint disease in murine arthritis.
48 patients with knee OA (ACR criteria) Kellgren and Lawrence (KL) score ≥2 and average daily pain score 4–9 by 11-point numerical rating scale (NRS), were randomized (1:1) to weekly subcutaneous (SC) GSK3858279 or placebo (PBO) for 8 weeks. Besides pharmacokinetic and immunogenicity data exploratory endpoints included change from baseline of pain in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index pain and function score).
For the primary endpoints of average and worst knee pain intensity, GSK3858279 showed greater improvement versus PBO at all timepoints. At day 57, the difference (95% CI) in change from baseline in the WOMAC for GSK3858279 versus PBO was −1.41 for pain and −1.29 for function. There were no serious AEs or deaths.
Weekly dosing for 8 weeks with GSK3858279, a new mode of action inhibiting the chemokine CCL17, has clinical activity (improved pain scores) and a favourable safety profile in patients with osteoarthritis of the knee. These compelling data warrant further study of the effectiveness and safety.