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The safety and efficacy of Hyruan ONE (test product), an intra-articular cross-linked sodium hyaluronate injection, to treat mild-to-moderate knee osteoarthritis was compared with that of Durolane (comparator) in a prospective, active-controlled, parallel-group, double-blind (masked-observed), multicenter non-inferiority study. European patients (n = 284) were randomized 1:1 (test product:comparator) and received one injection of cross-linked hyaluronic acid (60 mg/3 mL). In total, 280 patients completed the study. The primary endpoint of mean change in Western Ontario and McMaster University (WOMAC)–Likert Pain sub-scores from baseline at week 13 revealed changes of −5.59 and −5.54 for the test and comparator groups, respectively, demonstrating non-inferiority of the test product (difference, −0.05 [95% confidence interval, −0.838 to 0.729]). Secondary endpoint results, which included changes in WOMAC–Likert Pain sub-score from baseline to 26 weeks post-injection and changes in WOMAC–Likert Total score and Physical Function and Stiffness sub-scores, changes in patients’ and investigators’ global assessments, use of rescue medication, and responder rates at 13 and 26 weeks post-injection were similar between the groups. Incidence of adverse events was also similar. In both groups, most treatment-emergent adverse events were mild/moderate. Hyruan ONE was non-inferior to the comparator at 13 weeks post-injection in European patients with mild-to-moderate knee osteoarthritis.

Introduction The objective of this study was to compare a single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) versus placebo in treating moderate-to-severe symptomatic knee osteoarthritis. Methods Subjects with primary osteoarthritis knee pain (Kellgren and Lawrence grade 2–3) were randomly assigned to intra-articular HA-HL or placebo in a prospective, double-blind, 24-week study. The primary outcome variable was change from screening to week 24 of a Visual Analogue Scale (VAS) pain score. Secondary outcomes included Lequesne’s algofunctional index, EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L), Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) response and rescue medication usage. Results In a total of 692 randomized patients, a rapid decrease was observed in mean VAS pain score from baseline to week 1 (26 ± 24 mm in the HA-HL group vs. 23 ± 23 mm in the placebo group); pain intensity continued to decrease during 24 weeks of follow-up, reaching a mean change from baseline of 35 ± 28 mm vs. 32 ± 27 mm at week 24. Mixed model analysis demonstrated statistically significant differences between groups in favor of the HA-HL group at weeks 1, 6, 12, and 24. HA-HL was also more effective than placebo in improving Lequesne’s algofunctional index, OMERACT-OARSI response, and health-related quality of life. The use of rescue medication (paracetamol 500 mg tablets; ≤ 6 per day) was lower in the HA-HL group. Both treatments were similarly well tolerated. Conclusions A single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) is effective in providing fast, sustained, and clinically relevant reductions in pain, functional limitation, and health-related quality of life that were apparent at 1 week after the intra-articular injection and maintained throughout the 24-week follow-up in subjects with painful knee osteoarthritis, with a good safety profile. Trial Registration ClinicalTrials.gov identifier: NCT03200288. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00363-3.