A phase III, randomised, double-blind, multi-dose, placebo- and naproxen-controlled study to evaluate the efficacy and safety of fasinumab in patients with pain due to osteoarthritis of the knee or hip

Background Chronic pain due to osteoarthritis (OA) causes considerable burden, and current treatment options are limited. This phase III study aimed to compare the efficacy and safety of fasinumab, an investigational, anti-nerve growth factor monoclonal antibody, with placebo and naproxen in patients with moderate-to-severe pain due to OA of the knee or hip. Methods Patients with difficult-to-treat OA were randomised 3:3:3:1 to fasinumab 1 mg subcutaneous (SC) every 4 weeks (Q4W), fasinumab 1 mg SC every 8 weeks (Q8W), naproxen 500 mg orally two times a day or placebo. The co-primary endpoints were changes in Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain and physical function subscale scores (0–10) from baseline to week 16 for fasinumab versus placebo; comparison with naproxen was a secondary endpoint. Safety was also assessed. Results Of 3307 patients randomised, 1801 were included in the analysis for efficacy, and 3014 were included in the safety analysis. Statistically significantly greater reductions in the WOMAC pain and physical function scores, respectively, at week 16 were seen for fasinumab 1 mg Q4W (–2.90 and –2.78) compared with placebo (–2.32 and –2.10) and naproxen (−2.61 and –2.41); all p<0.005. Adjudicated arthropathies (AAs) and joint replacements occurred in all treatment groups, but were higher in the fasinumab 1 mg Q8W and 1 mg Q4W groups than in the placebo and naproxen groups. Patients with AAs: 7.2%, 9.7%, 1.1% and 2.6%, respectively; patients with joint replacements: 5.6%, 6.4%, 3.4% and 3.1%, respectively. Of the AAs in the fasinumab arms, 95.0% and 75.5% were rapid-progressive OA type 1 in the 1 mg Q8W and 1 mg Q4W arms, respectively. No new safety concerns were identified. Conclusion In a difficult-to-treat population with OA, fasinumab 1 mg Q4W achieved clinically meaningful improvements by week 16 versus placebo and naproxen. The safety profile was similar to that previously observed for fasinumab. Trial registration number NCT03161093 .