Department of Gynecology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Department of Gynecology, The First Affiliated Hospital of Xi'an Medical College, Shaanxi, China.
Infection. 2024 Oct;52(5):1787-1797. doi: 10.1007/s15010-024-02233-w. Epub 2024 Apr 3.
To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC).
A 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.
In 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.
As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG.
CTR20220918.
评估口服伊布列康唑（HS-10366）在患有阴道念珠菌病（VVC）的中国患者中的疗效和安全性。
在有症状的 VVC 患者中进行了一项双盲、安慰剂对照、随机、多中心的 III 期研究。患者接受每日两次口服伊布列康唑 300mg 或匹配安慰剂治疗 1 天（2:1）。主要终点为治疗结束时（TOC）第 11±3 天的临床治愈（VSS 评分=0）。次要终点包括 TOC 时的真菌学清除率、总体反应和临床改善（VSS 评分≤1），以及 TOC 后第 25±4 天的阴道症状缓解。
共有 360 例患者被纳入改良意向治疗人群（定义为阳性念珠菌培养且至少接受一种研究药物的患者；伊布列康唑组 239 例，安慰剂组 121 例）。与安慰剂相比，接受伊布列康唑治疗的患者临床治愈率（51.0% vs. 25.6%）、真菌学清除率（55.6% vs. 18.2%）、总体反应率（33.9% vs. 8.3%）在 TOC 时更高，且在随访时完全症状缓解率（74.5% vs. 39.7%）更高（均 P<0.001）。临床治愈率的亚组分析表明，C. albicans 患者可从伊布列康唑治疗中获益。事后分析也表明，非白念珠菌念珠菌患者也有类似的获益趋势。进一步分析显示，对于临床治愈和真菌学清除，伊布列康唑在氟康唑不敏感的 C. albicans 和氟康唑敏感的 C. albicans 患者中的疗效相似。伊布列康唑总体耐受性良好。不良事件主要为胃肠道，且主要为轻度。
作为一种新型抗真菌药物，伊布列康唑在治疗中国患者的阴道念珠菌病方面具有良好的疗效和安全性。
