Abstract：
OBJECTIVE: Vilaprisan is a highly potent selective progesterone receptor modulator shown to reduce heavy menstrual bleeding, induce amenorrhea, and diminish uterine fibroid volume in phase 2 studies. The objective of ASTEROID 3 was to demonstrate the superiority of vilaprisan compared with placebo in the treatment of heavy menstrual bleeding in women with uterine fibroids.
METHODS: Randomized, double-blind, placebo-controlled, multicenter phase 3 study.
METHODS: Hospitals and medical centers.
METHODS: Women with ≥1 uterine fibroid of ≥3 cm and heavy menstrual bleeding of >80 mL/cycle.
METHODS: Women were randomly assigned to 1 of 4 treatment arms, which were planned to comprise 2 treatment periods of 12 weeks, each with vilaprisan (2 mg/d) or placebo that were continuous or separated by a break of one bleed.
METHODS: Amenorrhea (primary end point; <2 mL in the last 28 days of treatment) and heavy menstrual bleeding response (key secondary end point; <80 mL/cycle and >50% reduction in bleeding from baseline) were measured with the alkaline hematin method. Change in volume of the 3 largest fibroids from baseline to end of treatment was assessed by ultrasound. Safety was monitored throughout the study.
RESULTS: Overall, 75 women completed the first 12 weeks of treatment. Statistically significant and clinically meaningful differences were observed between the vilaprisan- and placebo-treated groups in both the full analysis and per-protocol sets. In the per-protocol set (n = 36 and n = 12 for the vilaprisan and placebo groups, respectively), amenorrhea was observed more frequently in women treated with vilaprisan than in those who received placebo (83.3% vs. 0%, P<.0001), with a median time to onset of 3 days in the vilaprisan group. Similarly, more vilaprisan- than placebo-treated women achieved a response in heavy menstrual bleeding (91.7% vs. 25.0%, P<.0001). Serious adverse events were reported for 22 (27.8%) of 79 women and were evenly distributed among the 4 groups receiving vilaprisan and/or placebo. None of these events led to study discontinuation or were related to the liver, and no new safety findings were identified compared with the earlier phase 2 ASTEROID studies.
CONCLUSIONS: Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted.
BACKGROUND: NCT03400943 (ClinicalTrials.gov).
METHODS: Randomized, double-blind, placebo-controlled, multicenter phase 3 study.
METHODS: Hospitals and medical centers.
METHODS: Women with ≥1 uterine fibroid of ≥3 cm and heavy menstrual bleeding of >80 mL/cycle.
METHODS: Women were randomly assigned to 1 of 4 treatment arms, which were planned to comprise 2 treatment periods of 12 weeks, each with vilaprisan (2 mg/d) or placebo that were continuous or separated by a break of one bleed.
METHODS: Amenorrhea (primary end point; <2 mL in the last 28 days of treatment) and heavy menstrual bleeding response (key secondary end point; <80 mL/cycle and >50% reduction in bleeding from baseline) were measured with the alkaline hematin method. Change in volume of the 3 largest fibroids from baseline to end of treatment was assessed by ultrasound. Safety was monitored throughout the study.
RESULTS: Overall, 75 women completed the first 12 weeks of treatment. Statistically significant and clinically meaningful differences were observed between the vilaprisan- and placebo-treated groups in both the full analysis and per-protocol sets. In the per-protocol set (n = 36 and n = 12 for the vilaprisan and placebo groups, respectively), amenorrhea was observed more frequently in women treated with vilaprisan than in those who received placebo (83.3% vs. 0%, P<.0001), with a median time to onset of 3 days in the vilaprisan group. Similarly, more vilaprisan- than placebo-treated women achieved a response in heavy menstrual bleeding (91.7% vs. 25.0%, P<.0001). Serious adverse events were reported for 22 (27.8%) of 79 women and were evenly distributed among the 4 groups receiving vilaprisan and/or placebo. None of these events led to study discontinuation or were related to the liver, and no new safety findings were identified compared with the earlier phase 2 ASTEROID studies.
CONCLUSIONS: Vilaprisan is efficacious and well tolerated over 12 weeks in the treatment of heavy menstrual bleeding associated with uterine fibroids. Further investigations of the long-term efficacy and safety of vilaprisan are warranted.
BACKGROUND: NCT03400943 (ClinicalTrials.gov).
摘要：
目的：Vilaprisan是一种高效的选择性孕激素受体调节剂，可减少大量月经出血，诱发闭经,并在2期研究中减少子宫肌瘤体积。ASTEROID3的目的是证明vilaprisan与安慰剂相比在治疗子宫肌瘤女性月经大量出血方面的优越性。
方法：随机化，双盲,安慰剂对照,多中心3期研究。
方法：医院和医疗中心。
方法：患有≥1个子宫肌瘤≥3cm且月经大出血>80mL/周期的女性。
方法：将妇女随机分配到4个治疗组中的1个，计划包括2个为期12周的治疗期，每个服用维拉普生（2mg/d）或安慰剂，连续或一次出血中断。
方法：闭经（主要终点；治疗最后28天<2mL）和重度月经出血反应（关键次要终点；<80mL/周期和比基线出血减少>50%）采用碱性血色素法测定。通过超声评估从基线到治疗结束的3个最大肌瘤的体积变化。在整个研究中监测安全性。
结果：总体而言，75名妇女完成了前12周的治疗。在完整分析和符合方案集合中，在vilaprisan和安慰剂治疗组之间观察到统计学上的显着和临床意义的差异。在符合方案的集合中（vilaprisan和安慰剂组的n=36和n=12，分别)，在接受vilaprisan治疗的女性中，闭经的发生率高于接受安慰剂的女性（83.3％vs.0%,P<.0001),vilaprisan组的中位发病时间为3天。同样，比安慰剂治疗的女性更多的vilaprisan-在月经大出血中获得了缓解(91.7%vs.25.0%,P<.0001)。据报道，79名妇女中有22名（27.8％）发生严重不良事件，并平均分布在接受vilaprisan和/或安慰剂的4组中。这些事件均未导致研究中止或与肝脏有关，与早期的2期ASTEROID研究相比,未发现新的安全性发现.
结论：Vilaprisan在治疗与子宫肌瘤相关的大量月经出血的12周内有效且耐受性良好。有必要对vilaprisan的长期疗效和安全性进行进一步研究。
背景：NCT03400943（ClinicalTrials.gov）。
方法：随机化，双盲,安慰剂对照,多中心3期研究。
方法：医院和医疗中心。
方法：患有≥1个子宫肌瘤≥3cm且月经大出血>80mL/周期的女性。
方法：将妇女随机分配到4个治疗组中的1个，计划包括2个为期12周的治疗期，每个服用维拉普生（2mg/d）或安慰剂，连续或一次出血中断。
方法：闭经（主要终点；治疗最后28天<2mL）和重度月经出血反应（关键次要终点；<80mL/周期和比基线出血减少>50%）采用碱性血色素法测定。通过超声评估从基线到治疗结束的3个最大肌瘤的体积变化。在整个研究中监测安全性。
结果：总体而言，75名妇女完成了前12周的治疗。在完整分析和符合方案集合中，在vilaprisan和安慰剂治疗组之间观察到统计学上的显着和临床意义的差异。在符合方案的集合中（vilaprisan和安慰剂组的n=36和n=12，分别)，在接受vilaprisan治疗的女性中，闭经的发生率高于接受安慰剂的女性（83.3％vs.0%,P<.0001),vilaprisan组的中位发病时间为3天。同样，比安慰剂治疗的女性更多的vilaprisan-在月经大出血中获得了缓解(91.7%vs.25.0%,P<.0001)。据报道，79名妇女中有22名（27.8％）发生严重不良事件，并平均分布在接受vilaprisan和/或安慰剂的4组中。这些事件均未导致研究中止或与肝脏有关，与早期的2期ASTEROID研究相比,未发现新的安全性发现.
结论：Vilaprisan在治疗与子宫肌瘤相关的大量月经出血的12周内有效且耐受性良好。有必要对vilaprisan的长期疗效和安全性进行进一步研究。
背景：NCT03400943（ClinicalTrials.gov）。
