Phase 3 N=229 Randomized Quadruple-blind Treatment

Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

Uterine Leiomyoma · Uterine Fibroids

Bottom Line

View on ClinicalTrials.gov: NCT03751124 ↗

Enrolled (actual)

229

Serious AEs

1.8%

Results posted

Jun 2024

Primary outcome: Primary: Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period — 78.43; 15.08 percentage of participants — p=<0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Relugolix (Drug); Estradiol/norethindrone acetate (Drug); Placebo for relugolix (Drug); Placebo for E2/NETA (Drug)
Age: Adult · 18+ yrs
Sex: Female
Sponsor: Myovant Sciences GmbH
Primary completion: Feb 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period	78.43; 15.08	<0.0001 sig
SECONDARY Time To MBL Volume ≥80 mL During The Randomized Treatment Period	NA; 5.9	<0.0001 sig
SECONDARY Percentage Of Participants Who Maintained MBL Volume Of <80 mL At Week 104 During The Randomized Treatment Period	69.79; 11.75	<0.0001 sig
SECONDARY Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 76 During The Randomized Treatment Period	57.39; 13.27	<0.0001 sig
SECONDARY Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period	6.6; 11.5	—
SECONDARY Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period	2.1; 3.9	—
SECONDARY Percentage Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period	652.0; 55.0	—
SECONDARY Percentage Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period	-42.0	—
SECONDARY Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 104 During The Randomized Treatment Period	58.26; 10.62	—
SECONDARY Percentage Of Participants Who Responded (MBL Volume <80 mL) To Retreatment During The Retreatment Period	96.15; 97.75	—
SECONDARY Percentage Of Participants Whose Menses Had Resumed During The Randomized Treatment Period	35.29; 91.54; 41.12; 92.75	—
SECONDARY Time To Resumption Of Menses For Participants Who Were Amenorrhoeic At Week 52/Baseline During The Randomized Treatment Period	NA; 5.4	—
SECONDARY Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period	0.3; -0.2	—
SECONDARY Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period	0.3; -0.2	—
SECONDARY Percentage Of Participants With MBL Volume Of ≥80 mL At Week 76 And Week 104 During the Randomized Treatment Period	21.57; 84.92; 30.21; 88.25	—
SECONDARY Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period	2.3; -0.7	—
SECONDARY Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period	2.3; -0.7	—
SECONDARY Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period	2.3; -0.7	—
SECONDARY Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period	5.08; 0	—
SECONDARY Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period	5.08; 0	—
SECONDARY Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period	6.78; 25.00	—
SECONDARY Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period	6.78; 25.00	—
SECONDARY Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period	0.5; 0.5; -0.5; -0.6; 1.9; 1.7	—
SECONDARY Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period	0.5; 0.5; -0.5; -0.6; 1.9; 1.7	—
SECONDARY Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period	0.8; -0.6; -0.8; 0.1	—
SECONDARY Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period	0.8; -0.6; -0.8; 0.1	—
SECONDARY Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period	0; 0; 0; 0; 3; 0	—
SECONDARY Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period	0; 0; 0; 0; 3; 0	—
SECONDARY Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period	0; 0; 1; 0; 1; 0	—
SECONDARY Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period	0; 0; 1; 0; 1; 0	—
SECONDARY 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	0.5; 0	—
SECONDARY 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	0.5; 0	—
SECONDARY 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	0; 5.0	—
SECONDARY 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	0; 5.0	—
SECONDARY 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	0.6; 6.0	—
SECONDARY 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	0.6; 6.0	—
SECONDARY 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	-1.3; 5.0	—
SECONDARY 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	-1.3; 5.0	—
SECONDARY Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period	-0.5; -6.3	—
SECONDARY Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period	-0.5; -6.3	—
SECONDARY Original: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period	2.2; 14.1	—
SECONDARY New: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period	0.1; -4.3	—
SECONDARY 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	2.2; 11.9; 0.9; 8.5; 0.6; 7.5	—
SECONDARY 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	2.2; 11.9; 0.9; 8.5; 0.6; 7.5	—
SECONDARY Predose Concentration Of Estradiol At Week 56	2.03; 62.54	—
SECONDARY Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability	68; 72; 2; 3; 1; 0	—
SECONDARY Percent Change From Week 52/Baseline In BMD At Lumbar Spine (L1-L4)	0.81; 0.10	—
SECONDARY Percent Change From Week 52/Baseline In BMD At Femoral Neck And Total Hip	0.34; -0.13; -0.19; -0.76	—

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.

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03751124). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.