Abstract
OBJECTIVE: To evaluate the efficacy and safety of diclofenac etalhyaluronate (DF-HA) (ONO-5704/SI-613), a novel DF-conjugated hyaluronate, in patients with knee OA in Japan. METHODS: In this randomized, double-blind, placebo-controlled phase 2 study, patients were randomly assigned (1:1) to receive either 30 mg of DF-HA or placebo intra-articularly at weeks 0, 4 and 8 and were followed up for 24 weeks. The primary outcomes were changes from baseline in the WOMAC pain subscores, 50-foot walk test pain score and daily pain score. The secondary outcomes were the WOMAC physical function subscores, patient global assessment, responder rate and safety outcome. RESULTS: Overall, 176 patients received the investigational drugs (87 received DF-HA and 89 received placebo). The mean changes in the WOMAC pain subscores and daily pain score from baseline over 12 weeks after the first injection were significantly higher in the DF-HA than placebo group; the mean difference was -7.0 mm [95% CI, -12.7, -1.2; P =0.018] and -0.61 (95% CI, -1.06, -0.16; P =0.008), respectively. The difference in the 50-foot walk test pain score was -5.0 mm (95% CI, -10.3, 0.3; P =0.065). Improvement of pain by DF-HA was observed at week 1 and maintained from week 12 to week 24. Significantly greater improvements in the secondary outcomes were also observed with DF-HA than with placebo. No clinically significant adverse events occurred. CONCLUSION: DF-HA reduced pain in patients with knee OA without major safety concerns. TRIAL REGISTRATION: UMIN Clinical Trials Registry, https://www.umin.ac.jp/ctr/index.htm, UMIN000015858.