Efficacy and safety of a single intra-articular injection of 6 ml Hylan G-F 20 compared to placebo in Chinese patients with symptomatic knee osteoarthritis : C-SOUND study, a 26-week multicenter double-blind randomized placebo-controlled trial in China

Yan Ke, Wenxue Jiang, Yongsheng Xu, Yajun Chen, Qingsong Zhang, Qingyun Xue, Jianhao Lin, Wilson Ngai, Gaowei Nian, Mir Sohail Fazeli, Yao Xie, Zhenan Zhu, Yan Ke, Wenxue Jiang, Yongsheng Xu, Yajun Chen, Qingsong Zhang, Qingyun Xue, Jianhao Lin, Wilson Ngai, Gaowei Nian, Mir Sohail Fazeli, Yao Xie, Zhenan Zhu

Abstract

Background: Single 6 ml Hylan G-F 20 injection, is indicated for knee osteoarthritis patients who have failed to respond to non-pharmacologic therapy and/or simple analgesics. To obtain more thorough understanding of the clinical efficacy and safety, a randomized clinical trial was conducted comparing intra-articular (IA) administration of single 6 ml Hylan G-F 20 injection versus placebo in knee OA patients of Chinese ethnicity.

Methods: This was a randomized, multi-center, double-blind, placebo-controlled clinical trial conducted in 21 centers across China. Four hundred forty adults with knee OA received a single 6 ml Hylan G-F 20 or placebo injection and were evaluated for clinical efficacy and safety outcomes over 26 weeks. Western Ontario and McMaster Universities OA (WOMAC) A1 index, treatment-emergent adverse events (TEAEs) and standard safety parameters were measured at pre-injection, and at weeks 1, 4, 8, 12, 16, 20 and 26 post-injection.

Results: Four hundred forty patients (male: 98 [22.3%]; female: 342 [77.7%]) were randomized. The mean age [standard deviation (SD)] was 61.5 (7.9) years. All patients were of East Asian ethnicity. Mean WOMAC A1 score at baseline was 5.3 (1.2) and 5.2 (1.3) in single 6 ml Hylan G-F 20 injection and placebo groups, respectively. Significant reductions of WOMAC A1 score were observed in both treatment groups when compared to baseline at 26 weeks post-injection, with the mean reduction of [standard error (SE)/percentage] -2.146 (0.108)/- 40.5% and - 2.271 (0.110) /- 43.7% in the single 6 ml Hylan G-F 20 injection and the placebo groups, respectively. Additionally, clinically important reductions in pain at 26 weeks was reported in 67.0 and 68.2% in single 6 ml Hylan G-F 20 injection and placebo groups (p = 0.36). Regarding safety, TEAEs were similar between the two treatment groups (hylan G-F 20 single: 61.5%; placebo: 64.5%).

Conclusions: While the magnitude of the effect of a single 6 ml Hylan G-F 20 injection in this study is consistent with previously published literature with respect to the efficacy and safety of the drug, the current study shows a strong IA placebo effect and did not established superiority of single 6 ml Hylan G-F 20 injection over IA placebo in Chinese knee OA patients.

Trial registration: Prospectively registered Jun 16, 2017 at www.clinicaltrials.gov ( NCT03190369 ).

Keywords: Clinical outcomes; Knee osteoarthritis; Placebo effect; Single 6 ml Hylan G-F 20 injection.

Conflict of interest statement

Authors Yan Ke, Wenxue Jiang, Yongsheng Xu, Yajun Chen, Qingsong Zhang, Qingyun Xue, Jianhao Lin, and Zhenan Zhu declare that they have no conflicts of interest. Authors Wilson Ngai, Gaowei Nian and Yao Xie are employees of Sanofi and hold shares in the company.

Figures

Fig. 1
Fig. 1
Flowchart of study population recruitment
Fig. 2
Fig. 2
WOMAC A1: Least square Means (SE) for change from baseline over time. Least-square (LS) means and standard errors (SE) are taken from repeated measures of Covariance analysis. The model includes treatment groups (Single 6 ml Hylan G-F 20 injection and placebo), site, visit and visit by treatment interaction, as well as the baseline WOMAC A1 score as a covariate. Included are patients who have measurements at baseline and at least one post-baseline value

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