Abstract
<title>Abstract</title> <p> <bold>Background:</bold> LBSA0103 (Synovian <sup>®</sup> ) is a high molecular weight single-injection intra-articular hyaluronic acid product crosslinked by 1,4-butanediol diglycidyl ether (BDDE). This randomized, double-blind, multi-center, non-inferiority study was conducted to evaluate the efficacy and safety of this single-injection intra-articular hyaluronic acid (LBSA0103) compared with a three-injection intra-articular hyaluronic acid (Synvisc <sup>®</sup> ) in patients with knee osteoarthritis (OA). <bold>Methods:</bold> 265 patients with knee osteoarthritis were enrolled and randomized to receive three injections of Synvisc <sup>®</sup> , or three injections of LBSA0103 (including two sham injections), all at weekly intervals. Patients were followed up at 1 week, 6 weeks, 13 weeks, and 26 weeks after the last injection. The main endpoint was the change of WOMAC-Likert pain score from baseline to 13 weeks after the last injection. The noninferiority was assessed with a margin of 1.6. Other outcome measures were the WOMAC-Likert subscale and total scores; global evaluations by both the patient and investigator; physical examinations; proportion of patients taking rescue medicines; and remission rate in accordance with OMERACT-OARSI standards. <bold>Results:</bold> The WOMAC-Likert pain scores decreased from baseline to 13 weeks after the last injection with -7.43 and -6.79 respectively for the LBSA0103 and Synvisc groups, indicating a significantly greater decrease in the LBSA0103 group ( <italic>p</italic> =0.039). The upper limit of 97.5% CI was below the margin of 1.6, confirming the noninferiority of LBSA0103 to Synvisc. The changes of all secondary endpoints at the follow-up visits consistently indicated a general improvement in two groups. Most of them were found no significant differences between the groups, except the changes of WOMAC-Likert pain score, investigator's global assessment and range of motion assessment in the knee from baseline to 26 weeks after the last injection. The safety profile of two groups were comparable and no new safety issue was identified. <bold>Conclusions:</bold> The single-injection of BDDE-crosslinked LBSA0103 is noninferior to a three injections of Synvisc <sup>®</sup> at weekly intervals, providing support that LBSA0103 is a safe and effective option in managing Chinese patients with mild to moderate OA of knee. <bold>Trial registration:</bold> This study was registered at www.chictr.org.cn with the registration number ChiCTR2400090323 on 27/09/2024. </p>