Efficacy and Safety of Intra-Articular Hyaluronic Acid Injection (NRD101 / SUVENYL®) in Patients With Knee Osteoarthritis: a Multicenter, Randomized, Double-blind, Parallel, Active Control, Non-Inferiority Clinical Study

Abstract BackgroundIntra-articular injection of hyaluronic acid (HA) has favorable effects on pain relief and knee function along with the low incidence of serious adverse reactions. Although various HA products are available for the treatment of knee osteoarthritis, it is still controversial whether differences in HA products have any clinically significant difference in efficacy and safety. In light of the above, the efficacy and safety of intra-articular injection of biological fermentation–derived high-molecular-weight HA (NRD101) was investigated in a double-blind comparative manner in Chinese patients with knee osteoarthritis.MethodA multicenter, prospective, randomized, double-blind, parallel, active control, non-inferiority study was conducted in Chinese patients with knee osteoarthritis. Patients were randomized to receive five consecutive weekly injections of either NRD101 or Artz (a non-crosslinked low-molecular-weight HA derived from combs of roosters) followed by 4 weeks follow-up. The primary efficacy endpoint was the change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) NRS pain subscale score at Week 5. Secondary efficacy endpoints included WOMAC stiffness and physical function subscale score, local pain, range of joint motion, and overall improvement.ResultsAmong 267 randomized patients, 259 patients completed the study. The change from baseline in WOMAC NRS pain subscale score at Week 5 was −2.98 ± 0.193 in the NRD101 group and −2.66 ± 0.194 in the Artz group, and the trial met the non-inferiority criteria. Efficacy in the NRD101 group tended to be consistently higher than in the Artz group for most items of WOMAC. Several subgroup analyses also showed differences between the two groups, tending to favor NRD101. Adverse events were seen in 26.0% (34/131) of patients in the NRD101 group and 38.3% (51/133) in the Artz group.ConclusionsNRD101 improved knee pain in Chinese patients with osteoarthritis after five consecutive weekly injections. NRD101 tended to be somewhat more effective than Artz. No new safety concerns were identified.Trial registration: JapicCTI, JapicCTI-173531. Registered 10 March 2017, https://www.clinicaltrials.jp/cti-user/trial/Search.jsp