Article
作者: Shi, Hong ; Chen, Lihong ; Xu, Dabao ; Song, Weihua ; Liao, Qinping ; Zhang, Chun ; Wang, Wenying ; Wang, Xiaoli ; Li, Jingjing ; An, Ruifang ; Wu, Qiong ; Qiu, Jin ; Shi, Ling ; Li, Yingxiong ; Luo, Xiaowan ; Wang, Baojin ; Zhang, Chunlian ; Ye, Hong ; Ruan, Hongjie ; Patiman, Mijiti ; Wang, Gang ; Ruan, Qi ; Zhang, Songling ; Xu, Hongyan ; Wang, Xiaoqian ; Wang, Xu ; Li, Chuan ; Lu, Jing ; Jia, Wen ; Zhang, Bei ; Hu, Lina ; Lin, Jiajing ; Xue, Fengxia ; Qian, Sumin ; Wang, Shijin
AbstractPurposeTo evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC).MethodsA double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4.ResultsIn total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity.ConclusionsAs a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients.Chinadrugtrials.org.cn registry numberCTR20220918.