Goje Oluwatosin, Azie Nkechi E, Angulo David A, Sobel Ryan, Nyirjesy Paul, Sobel Jack D
Obstetrics and Gynecology Institute, Cleveland Clinic Foundation, Cleveland, OH.
Department of Reproductive Infectious Diseases, SCYNEXIS, Inc., Jersey City, NJ.
Am J Obstet Gynecol. 2025 Aug 5. doi: 10.1016/j.ajog.2025.07.040.
Recurrent vulvovaginal candidiasis develops in 5% to 9% of people assigned female at birth and has a serious impact on quality of life. Oral ibrexafungerp is a first-in-class, nonazole, triterpenoid antifungal approved in the United States for the treatment of postmenarchal females with acute vulvovaginal candidiasis and for the reduction in the incidence of recurrent vulvovaginal candidiasis.
This phase 3 study (CANDLE) describes the efficacy and safety of monthly oral ibrexafungerp vs placebo for reducing the incidence of recurrent vulvovaginal candidiasis.
Participants with a history of recurrent vulvovaginal candidiasis experiencing an acute infection episode (confirmed by positive potassium hydroxide test) received 3 doses of oral fluconazole (150 mg once-daily every 3 days). Those who had culture-confirmed vulvovaginal candidiasis from the screening sample achieved substantial resolution of signs and symptoms (composite Vulvovaginal Signs and Symptoms score≤2) following fluconazole treatment and continued to meet all study eligibility criteria, entered a maintenance phase. In the maintenance phase, eligible participants were randomized (1:1) to oral ibrexafungerp (300 mg twice-daily for 1 day) or placebo, which was repeated once every 4 weeks for a total of 6 treatments (until week 20). Efficacy was assessed by the percentage of participants with no mycologically proven recurrence and the percentage of participants with clinical success (a participant with a Test-of-Cure [week 24] evaluation and no recurrence; mycologically proven, presumed, or suspected) by Test-of-Cure (4 weeks after last study drug dose). Safety and tolerability assessments included incidence of adverse events and treatment discontinuations. Participants were further assessed for recurrence during a 12-week follow-up phase.
In the intent-to-treat population, 70.8% (n=92/130) of participants who received ibrexafungerp and 58.5% (n=76/130) who received placebo had no mycologically proven recurrence by Test-of-Cure (relative risk, 1.22; 95% confidence interval, 1.032, 1.430; P=0.019). The proportion of participants who achieved clinical success by Test-of-Cure was 65.4% (n=85/130) with ibrexafungerp and 53.1% (n=69/130) with placebo (relative risk, 1.24; 95% confidence interval, 1.034, 1.486; P=0.020). The benefit of ibrexafungerp over placebo was sustained over the 4 months following last study drug dose for both the no mycologically proven recurrence (65.4% [n=85/130] vs 53.8% [n=70/130]; relative risk, 1.22; 95% confidence interval, 1.021, 1.456; P=0.029) and clinical success (57.7% [n=75/130] vs 46.2% [n=60/130]; relative risk, 1.26; 95% confidence interval, 1.017, 1.555; P=0.034) endpoints. Overall, 64.6% (n=84/130) of participants who received ibrexafungerp and 58.5% (n=76/130) of participants who received placebo experienced ≥1 treatment-emergent adverse event. Treatment-related adverse events occurred in 14.6% (n=19/130) of participants in the ibrexafungerp group and 6.9% (n=9/130) of participants in the placebo group. No adverse events in the ibrexafungerp group led to treatment or study discontinuation. The most common adverse events reported in both the ibrexafungerp and placebo groups were headache, bacterial vaginosis, and diarrhea; these events were mostly mild in severity.
Once-monthly oral ibrexafungerp was effective and well-tolerated in participants with recurrent vulvovaginal candidiasis.
复发性外阴阴道念珠菌病在5%至9%的出生时被指定为女性的人群中发生，对生活质量有严重影响。口服伊曲康唑是一种一流的非唑类三萜类抗真菌药物，在美国被批准用于治疗初潮后患有急性外阴阴道念珠菌病的女性，并用于降低复发性外阴阴道念珠菌病的发病率。
这项3期研究（CANDLE）描述了每月口服伊曲康唑与安慰剂相比在降低复发性外阴阴道念珠菌病发病率方面的疗效和安全性。
有复发性外阴阴道念珠菌病病史且经历急性感染发作（通过氢氧化钾试验阳性确认）的参与者接受3剂口服氟康唑（150毫克，每3天每日一次）。那些筛查样本经培养确诊为外阴阴道念珠菌病的参与者在氟康唑治疗后体征和症状得到显著缓解（外阴阴道体征和症状综合评分≤2）且继续符合所有研究纳入标准，进入维持阶段。在维持阶段，符合条件的参与者被随机分配（1:1）接受口服伊曲康唑（300毫克，每日两次，共1天）或安慰剂，每4周重复一次，共进行6次治疗（直至第20周）。通过无真菌学证实复发的参与者百分比以及治愈试验（末次研究药物剂量后4周）评估临床成功（接受治愈试验[第24周]评估且无复发；真菌学证实、推定或疑似）的参与者百分比来评估疗效。安全性和耐受性评估包括不良事件发生率和治疗中断情况。在12周的随访阶段对参与者的复发情况进行进一步评估。
在意向性治疗人群中，接受伊曲康唑的参与者中有70.8%（n = 92/130）在治愈试验中无真菌学证实的复发，接受安慰剂的参与者中有58.5%（n = 76/130）无真菌学证实的复发（相对风险，1.22；95%置信区间，1.032，1.430；P = 0.019）。通过治愈试验实现临床成功的参与者比例，接受伊曲康唑的为65.4%（n = 85/130），接受安慰剂的为53.1%（n = 69/130）（相对风险，1.24；95%置信区间，1.034，1.486；P = 0.020）。在末次研究药物剂量后的4个月内，伊曲康唑相对于安慰剂在无真菌学证实复发（65.4% [n = 85/130] 对53.8% [n = 70/130]；相对风险，1.22；95%置信区间，1.021，1.456；P = 0.029）和临床成功（57.7% [n = 75/130] 对46.2% [n = 60/130]；相对风险，1.26；95%置信区间，1.017，1.555；P = 0.034）终点方面的益处持续存在。总体而言，接受伊曲康唑的参与者中有64.6%（n = 84/130）经历了≥1次治疗中出现的不良事件，接受安慰剂的参与者中有58.5%（n = 76/130）经历了≥1次治疗中出现的不良事件。伊曲康唑组中14.6%（n = 19/130）的参与者和安慰剂组中6.9%（n = 9/130）的参与者发生了与治疗相关的不良事件。伊曲康唑组中没有不良事件导致治疗或研究中断。伊曲康唑组和安慰剂组报告最常见的不良事件是头痛、细菌性阴道病和腹泻；这些事件大多为轻度。
每月一次口服伊曲康唑对复发性外阴阴道念珠菌病患者有效且耐受性良好。
