透明质酸结合型双氯芬酸（双氯芬酸依托透明质酸钠）治疗膝关节骨关节炎的随机 2 期研究。

Sustained-release diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate) for knee osteoarthritis: a randomized phase 2 study.

机构信息

Department of Rehabilitation, Orthopaedic Surgery, Nagoya University Hospital, Nagoya, Japan.

Research & Development Division, Clinical Development Department, Seikagaku Corporation, Tokyo, Japan.

出版信息

Rheumatology (Oxford). 2021 Mar 2;60(3):1435-1444. doi: 10.1093/rheumatology/keaa605.

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.

目的

评估新型二氟尼柳结合透明质酸钠（DF-HA）（ONO-5704/SI-613）在日本膝骨关节炎（OA）患者中的疗效和安全性。

方法

在这项随机、双盲、安慰剂对照的 2 期研究中，患者按 1:1 比例随机分配（1:1）接受关节内注射 30mgDF-HA 或安慰剂，分别在第 0、4 和 8 周进行，随访 24 周。主要结局是自基线起 WOMAC 疼痛评分、50 英尺步行试验疼痛评分和每日疼痛评分的变化。次要结局为 WOMAC 躯体功能评分、患者整体评估、应答率和安全性结局。

结果

总体而言，176 例患者接受了研究药物治疗（87 例接受 DF-HA，89 例接受安慰剂）。首次注射后 12 周，WOMAC 疼痛评分和每日疼痛评分的平均变化在 DF-HA 组显著高于安慰剂组；平均差值为-7.0mm（95%置信区间：-12.7，-1.2；P=0.018）和-0.61（95%置信区间：-1.06，-0.16；P=0.008）。50 英尺步行试验疼痛评分差值为-5.0mm（95%置信区间：-10.3，0.3；P=0.065）。DF-HA 可在第 1 周观察到疼痛改善，并在第 12 周至第 24 周持续改善。DF-HA 组的次要结局也显著优于安慰剂组。未发生有临床意义的不良事件。