Linzagolix for Japanese women with uterine fibroids: a randomized, double-blind, placebo-controlled, phase 3 trial

IF 2.2

FS Reports Pub Date : 2026-10-01 Epub Date: 2026-07-21 DOI:10.1016/j.xfre.2026.07.003

Tasuku Harada M.D., Ph.D., Yutaka Osuga M.D., Ph.D., Hideomi Takahashi M.Ag., Asuka Kawai B.S., Fumiya Shimamura M.Eng.

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Secondary endpoints included time to a total PBAC score <10 or maximum NRS score ≤1, analgesic use, blood hemoglobin, myoma and uterine volumes, patient-reported symptom severity and quality of life, and plasma estradiol levels. Safety endpoints included adverse events (AEs) and time to menstrual recovery.</div></div><div>The primary endpoints were the proportion of patients with a total pictorial blood loss assessment chart (PBAC) score <10 from week 6–12, and the proportion of patients with a maximum numeric rating scale (NRS) score ≤1 during the 28 days before the end of treatment. Secondary endpoints included time to a total PBAC score <10 or maximum NRS score ≤1, analgesic use, blood hemoglobin, myoma and uterine volumes, patient-reported symptom severity and quality of life, and plasma estradiol levels. 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At the end of study treatment, mean plasma estradiol in the linzagolix group returned to pretreatment levels within 4 weeks, and the median time to menstrual recovery was 29 days.</div></div><div>The superiority of linzagolix vs. placebo was demonstrated for both the proportion of patients with a total PBAC score <10 from week 6–12 (91.5% vs. 2.5%; difference [95% confidence interval], 89.0% [76.0–96.2]), and the proportion of patients with a maximum NRS score ≤1 during the 28 days before the end of treatment (70.8% vs. 9.8%; difference, 61.1% [42.1–75.8]). Reductions in HMB and pain with linzagolix were rapidly achieved, occurred alongside improvements in other efficacy endpoints (e.g., analgesic use, blood hemoglobin, myoma and uterine volumes, patient-reported outcomes), and coincided with rapid and sustained reductions in plasma estradiol levels. 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引用次数: 0

Abstract

Objective

To evaluate the efficacy, safety, and pharmacodynamics of linzagolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, in patients with heavy menstrual bleeding (HMB) and pain because of uterine fibroids.

Design

Phase 3, multicenter, placebo-controlled, randomized, double-blind, parallel-group, confirmatory study (NCT05445167).

Subjects

Premenopausal Japanese women with HMB and moderate-to-severe pain because of uterine fibroids.

Intervention

Patients were randomized 1:1 to once-daily linzagolix 200 mg (n = 48) or placebo (n = 41) for 12 weeks.

Main Outcome Measures

The primary endpoints were the proportion of patients with a total pictorial blood loss assessment chart (PBAC) score <10 from week 6–12, and the proportion of patients with a maximum numeric rating scale (NRS) score ≤1 during the 28 days before the end of treatment. Secondary endpoints included time to a total PBAC score <10 or maximum NRS score ≤1, analgesic use, blood hemoglobin, myoma and uterine volumes, patient-reported symptom severity and quality of life, and plasma estradiol levels. Safety endpoints included adverse events (AEs) and time to menstrual recovery.

Results

The superiority of linzagolix vs. placebo was demonstrated for both the proportion of patients with a total PBAC score <10 from week 6–12 (91.5% vs. 2.5%; difference [95% confidence interval], 89.0% [76.0–96.2]), and the proportion of patients with a maximum NRS score ≤1 during the 28 days before the end of treatment (70.8% vs. 9.8%; difference, 61.1% [42.1–75.8]). Reductions in HMB and pain with linzagolix were rapidly achieved, occurred alongside improvements in other efficacy endpoints (e.g., analgesic use, blood hemoglobin, myoma and uterine volumes, patient-reported outcomes), and coincided with rapid and sustained reductions in plasma estradiol levels. The incidence of AEs was 91.7% in the linzagolix group and 75.6% with placebo; the most common AE in the linzagolix group was hot flush (47.9%). At the end of study treatment, mean plasma estradiol in the linzagolix group returned to pretreatment levels within 4 weeks, and the median time to menstrual recovery was 29 days.

Conclusion

These data reaffirm that GnRH receptor inhibition with linzagolix is a tolerable and efficacious strategy to manage the signs and symptoms of uterine fibroids.

Trial Registration

This trial was registered in clinicaltrials.gov, ID number NCT05445167. URL: https://clinicaltrials.gov/study/NCT05445167. Date of registration: 6/27/2022. Date of first enrollment: 10/11/2022.

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林扎哥利克斯用于日本子宫肌瘤妇女：一项随机、双盲、安慰剂对照的3期试验

目的评价口服促性腺激素释放激素（GnRH）受体拮抗剂linzagolix治疗子宫肌瘤所致重度月经出血（HMB）和疼痛的疗效、安全性和药效学。评估口服促性腺激素释放激素（GnRH）受体拮抗剂linzagolix在子宫肌瘤引起的重度月经出血（HMB）和疼痛患者中的疗效、安全性和药效学。设计3期，多中心，安慰剂对照，随机，双盲，平行组，验证性研究（NCT05445167）。3期，多中心，安慰剂对照，随机，双盲，平行组，验证性研究（NCT05445167）。研究对象：日本绝经前HMB患者和因子宫肌瘤引起的中度至重度疼痛。绝经前日本妇女HMB和中度至重度疼痛，因为子宫肌瘤。干预：患者按1:1的比例随机分配至每日一次的linzagolix 200mg （n = 48）或安慰剂（n = 41），持续12周。患者按1:1的比例随机分配至每日一次的linzagolix 200mg （n = 48）或安慰剂（n = 41），持续12周。主要终点为第6-12周总图像失血量评估表（PBAC）评分为&lt；10分的患者比例，以及治疗结束前28天最大数值评定量表（NRS）评分≤1分的患者比例。次要终点包括达到PBAC总分≤10或NRS总分≤1的时间、镇痛药的使用、血红蛋白、肌瘤和子宫体积、患者报告的症状严重程度和生活质量以及血浆雌二醇水平。安全性终点包括不良事件（ae）和月经恢复时间。主要终点为第6-12周总失血量评定图（PBAC）评分为&lt；10分的患者比例，以及治疗结束前28天最大数值评定量表（NRS）评分≤1分的患者比例。次要终点包括达到PBAC总分≤10或NRS总分≤1的时间、镇痛药的使用、血红蛋白、肌瘤和子宫体积、患者报告的症状严重程度和生活质量以及血浆雌二醇水平。安全性终点包括不良事件（ae）和月经恢复时间。结果在第6-12周PBAC总分≤10分的患者比例（91.5% vs. 2.5%，差异[95%置信区间]89.0%[76.0-96.2]）和治疗结束前28天NRS总分≤1分的患者比例（70.8% vs. 9.8%，差异61.1%[42.1-75.8]）均显示了linzagolix优于安慰剂的优势。使用linzagolix可迅速降低HMB和疼痛，同时改善其他疗效终点（例如，止痛药使用、血红蛋白、肌瘤和子宫体积、患者报告的结局），并与血浆雌二醇水平的快速和持续降低相一致。林扎哥利克斯组不良事件发生率为91.7%，安慰剂组为75.6%；linzagolix组最常见的AE为潮热（47.9%）。研究治疗结束时，林扎高利组平均血浆雌二醇在4周内恢复到治疗前水平，月经恢复的中位时间为29天。在第6-12周PBAC总分为&lt；10的患者比例（91.5% vs. 2.5%；差异[95%置信区间]89.0%[76.0-96.2]）和治疗结束前28天NRS评分最高≤1的患者比例（70.8% vs. 9.8%；差异61.1%[42.1-75.8]）均显示了linzagolix优于安慰剂的优势。使用linzagolix可迅速降低HMB和疼痛，同时改善其他疗效终点（例如，止痛药使用、血红蛋白、肌瘤和子宫体积、患者报告的结局），并与血浆雌二醇水平的快速和持续降低相一致。林扎哥利克斯组不良事件发生率为91.7%，安慰剂组为75.6%；linzagolix组最常见的AE为潮热（47.9%）。研究治疗结束时，林扎高利组平均血浆雌二醇在4周内恢复到治疗前水平，月经恢复的中位时间为29天。结论利扎哥利克抑制GnRH受体治疗子宫肌瘤是一种可耐受且有效的治疗方法。这些数据重申，GnRH受体抑制与林扎哥利克斯是一个可耐受和有效的策略来管理子宫肌瘤的体征和症状。本试验已在clinicaltrials.gov注册，ID号NCT05445167。URL: https://clinicaltrials.gov/study/NCT05445167。注册日期：6/27/2022。首次入学日期：10/11/2022。该试验已在clinicaltrials.gov注册，ID号NCT05445167。URL: https://clinicaltrials.gov/study/NCT05445167。注册日期：6/27/2022。首次入学日期：10/11/2022。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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