Safety and Efficacy of Fulranumab in Osteoarthritis of the Hip and Knee: Results From Four Randomized, Double-blind, Placebo-controlled Phase III Studies

Abstract

Purpose: To evaluate the safety and efficacy of fulranumab as adjunct or monotherapy in patients with knee or hip pain related to moderate-to-severe osteoarthritis. Methods: Osteoarthritic patients (aged ≥18 years) from 4 phase 3 randomized, double-blind (DB), placebo-controlled studies were randomized to receive placebo, fulranumab 1 mg every 4 weeks (Q4wk), or 3 mg Q4wk in 16-week DB phase, followed by a 52-week post-treatment follow-up phase. Safety assessments included treatment-emergent adverse events (TEAEs), and neurological, sympathetic and joint-related events of interest. Efficacy assessments included pain and physical function subscales of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Findings: Of 245 patients from the ITT set (median age, 64 years; women, 62%), 84 (34%) completed DB phase; the majority of discontinuations (57%) were due to early study termination. In DB phase, incidence of TEAEs in fulranumab 3 mg (57.8%) and 1 mg (56.8%) was similar to placebo (56.8%). Two events adjudicated as joint-related events of interest include rapidly progressive osteoarthritis and fracture of unknown etiology. There were no new neurological TEAEs. Fulranumab showed evidence of efficacy in improving pain and physical function based on WOMAC subscales scores. Due to premature study termination, the number of patients enrolled were too small to make any definitive efficacy claims. Implications: Treatment with fulranumab was generally tolerated with no new safety signals. Within the limited sample analyzed, fulranumab showed evidence of improvement of pain and function in patients with moderate-to-severe osteoarthritis who had failed prior therapy and were candidates for joint replacement surgery. Clinical trial registration numbers: NCT02336685, NCT02336698, NCT02289716, NCT02301234