An International Phase 3 Double-Blind, Placebo-Controlled, Randomized Withdrawal Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Overview
- Phase
- Phase 3
- Intervention
- Relugolix
- Conditions
- Uterine Leiomyoma
- Sponsor
- Myovant Sciences GmbH
- Enrollment
- 229
- Locations
- 94
- Primary Endpoint
- Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The objectives of this randomized withdrawal study are to evaluate the long-term efficacy and safety of the combination of relugolix, estradiol (E2) and norethindrone acetate (NETA), once daily, for up to 104 weeks in patients with uterine fibroids who have completed a total of 52 weeks of treatment, including a 24-week treatment period in a parent study (study MVT-601-3001 or MVT-601-3002) and a 28-week treatment period in the open-label extension study (MVT-601-3003), and who meet the definition of responder, defined as a patient who demonstrates a menstrual blood loss of < 80 mL and at least a 50% reduction from parent study baseline menstrual blood loss volume on the alkaline hematin analysis of the feminine products returned at Week 48 in the extension study.
Detailed Description
This randomized withdrawal study is an international phase 3 double-blind, placebo-controlled study that will enroll eligible patients with uterine fibroids who have completed the 24-week treatment period in a parent study (MVT-601-3001 or MVT-601-3002) and the 28-week treatment period of the open-label extension study (MVT-601-3003). When including treatment during the parent study and the extension study, patients completing this randomized withdrawal study will have received up to a total of 104 weeks of treatment with relugolix. Approximately 360 women with heavy menstrual bleeding associated with uterine fibroids completing the extension study with a response to treatment will be eligible to participate in this study. A responder is defined as a patient who demonstrates a menstrual blood loss of \< 80 mL and at least a 50% reduction from parent study baseline menstrual blood loss volume on the alkaline hematin analysis of the feminine products returned at Week 48 in the extension study. Screening procedures will be done on the same day as the Week 52 visit for the extension study. This visit will be referred to as the "Week 52/Baseline visit." When the Week 52/Baseline procedures in the extension study have been completed, the investigator will assess patient eligibility for participation in this study. The eligibility assessment will be based on data available at the Week 52/Baseline visit. Patients will be asked to provide feminine products for alkaline hematin analysis at each visit until the analysis confirms the return of heavy menstrual bleeding. The patients will then be offered retreatment with open-label relugolix with E2/NETA with the onset of the next menses. They will resume collection of feminine products for alkaline hematin analysis until two consecutive analyses confirm resolution of heavy menstrual bleeding (menstrual blood loss of \< 80 mL). Safety will be assessed throughout the study by monitoring adverse events, vital signs, physical examinations, clinical laboratory tests, and assessments of bone mineral density.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Completed the open-label extension study (MVT-601-3003).
- •Is a responder: Has a menstrual blood loss of \< 80 mL AND at least a 50% reduction from the parent study Baseline based on the results of the alkaline hematin testing performed on the feminine products returned at the Week 48 visit of the extension study.
- •Is not expected to undergo gynecological surgery or ablation procedures for uterine fibroids within the study period
Exclusion Criteria
- •Has undergone myomectomy, ultrasound-guided laparoscopic radiofrequency ablation, or any other surgical procedure for fibroids, uterine artery embolization, magnetic resonance guided focused ultrasound for fibroids, or endometrial ablation for abnormal uterine bleeding at any time during the Parent study or extension study.
- •Has a weight that exceeds the weight limit of the dual-energy x-ray absorptiometry (DXA) scanner
- •Has developed any contraindication to treatment with estradiol or norethindrone acetate
- •Is currently pregnant or lactating, or intends to become pregnant during the study period
- •Met a withdrawal criterion in the open-label extension (OLE) study.
Arms & Interventions
Relugolix plus E2/NETA
Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for up to 52 weeks.
Intervention: Relugolix
Relugolix plus E2/NETA
Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for up to 52 weeks.
Intervention: Estradiol/norethindrone acetate
Placebo tablets and capsules
* Placebo for relugolix co-administered with placebo for E2/NETA for up to 52 weeks or until heavy menstrual bleeding returns. * Retreatment with open-label relugolix with E2/NETA will be offered if heavy menstrual bleeding returns.
Intervention: Placebo for relugolix
Placebo tablets and capsules
* Placebo for relugolix co-administered with placebo for E2/NETA for up to 52 weeks or until heavy menstrual bleeding returns. * Retreatment with open-label relugolix with E2/NETA will be offered if heavy menstrual bleeding returns.
Intervention: Placebo for E2/NETA
Outcomes
Primary Outcomes
Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period
Time Frame: Week 52/Baseline up to Week 76
MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. The volume of MBL is measured in mL and a blood loss of 80 mL or more per cycle is considered diagnostic of heavy menstrual bleeding. The sustained responder rate was calculated as the Kaplan-Meier estimate of the cumulative probability of MBL volume \< 80 mL through Week 76 using the Kaplan-Meier method.
Secondary Outcomes
- Time To MBL Volume ≥80 mL During The Randomized Treatment Period(From Week 52/Baseline through Week 104)
- Percentage Of Participants Who Maintained MBL Volume Of <80 mL At Week 104 During The Randomized Treatment Period(Week 52/Baseline up to Week 104)
- Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 76 During The Randomized Treatment Period(Week 76)
- Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period(Week 52/Baseline to Week 76)
- Time To Resumption Of Menses For Participants Who Were Amenorrhoeic At Week 52/Baseline During The Randomized Treatment Period(Week 52/Baseline up to Week 104)
- Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Percentage Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Percentage Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period(Week 52/Baseline to Week 76)
- Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 104 During The Randomized Treatment Period(Week 104)
- Percentage Of Participants Who Responded (MBL Volume <80 mL) To Retreatment During The Retreatment Period(From Initiation of Retreatment to Week 104)
- Percentage Of Participants Whose Menses Had Resumed During The Randomized Treatment Period(Week 52/Baseline to Week 76 and Week 104)
- Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Percentage Of Participants With MBL Volume Of ≥80 mL At Week 76 And Week 104 During the Randomized Treatment Period(From Week 52/Baseline to Week 76 and Week 104)
- Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Work Time Missed Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period(Week 52/Baseline up to Week 104)
- Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Impairment While Working Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period(Week 52/Baseline up to Week 104)
- Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Overall Work Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period(Week 52/Baseline up to Week 104)
- Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Activity Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period(Week 52/Baseline up to Week 104)
- Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Original: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period(Week 52/Baseline to Week 76)
- New: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period(Week 52/Baseline to Week 104)
- Predose Concentration Of Estradiol At Week 56(Week 52/Baseline and Week 56)
- Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability(Week 52/Baseline up to Week 104)
- Percent Change From Week 52/Baseline In BMD At Lumbar Spine (L1-L4)(Week 52/Baseline to Week 104)
- Percent Change From Week 52/Baseline In BMD At Femoral Neck And Total Hip(Week 52/Baseline to Week 104)