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

Myovant Sciences

Status and phase: Completed; Phase 3

Conditions: Uterine Fibroids; Uterine Leiomyoma

Treatments: Drug: Relugolix; Drug: Estradiol/norethindrone acetate; Drug: Placebo for E2/NETA; Drug: Placebo for relugolix

Study type: Interventional

Funder types: Industry

Identifiers

NCT03751124

MVT-601-035

2018-001368-43 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 229 patients

Sex: Female

Ages: 18 to 51 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Completed the open-label extension study (MVT-601-3003).
2. 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.
3. Is not expected to undergo gynecological surgery or ablation procedures for uterine fibroids within the study period

Exclusion criteria

1. 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.
2. Has a weight that exceeds the weight limit of the dual-energy x-ray absorptiometry (DXA) scanner
3. Has developed any contraindication to treatment with estradiol or norethindrone acetate
4. Is currently pregnant or lactating, or intends to become pregnant during the study period
5. Met a withdrawal criterion in the open-label extension (OLE) study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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229 participants in 2 patient groups, including a placebo group

Relugolix plus E2/NETA

Experimental group

Description:

Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for up to 52 weeks.

Treatment:

Drug: Estradiol/norethindrone acetate

Drug: Relugolix

Placebo tablets and capsules

Placebo Comparator group

Description:

* 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.

Treatment:

Drug: Placebo for relugolix

Drug: Placebo for E2/NETA