LIBERTY EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

Study Overview
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Brief Summary
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The purpose of this study is to determine the long-term efficacy and safety of relugolix 40 milligrams (mg) once daily co-administered with low-dose estradiol (E2) and norethindrone acetate (NETA) for 28 weeks on heavy menstrual bleeding associated with uterine fibroids in participants who previously completed a 24-week treatment period in one of the parent studies (MVT-601-3001 or MVT-601-3002).

Detailed Description
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This study is an international phase 3 open-label, single-arm, long-term efficacy and safety extension study that will enroll eligible participants who have completed their participation in one of the phase 3 randomized, double-blind, placebo-controlled parent studies, MVT-601-3001 (LIBERTY 1 - NCT03049735) or MVT-601-3002 (LIBERTY 2 - NCT 03103087). All participants will receive relugolix 40 mg orally once daily co-administered with low-dose E2 (1.0 mg) and NETA (0.5 mg) for 28 weeks. Approximately 600 women with heavy menstrual bleeding associated with uterine fibroids will be enrolled, after having completed a 24-week treatment period in one of the parent studies. The objectives of the study are to evaluate long-term efficacy and safety through up to 52 weeks of treatment (including treatment during the parent study) of relugolix co-administered with low-dose E2/NETA. Screening and baseline procedures will be done at the same visit for this extension study (referred to as the Week 24/Baseline Visit), which coincides with the Week 24 Visit from the parent study, and will be defined as the date of completion of the last Week 24 procedure in the parent study. Participants will have received their last dose of study drug in the parent study on the day prior to the Week 24/Baseline Visit and will receive their first dose of study drug for this extension study in the clinic after the participant is determined to be eligible for this extension study and has provided informed consent to participate. The administration of the first dose of study drug for MVT-601-3003 will define enrollment into this study. Study participants will then take the open-label study treatment orally once daily for 28 weeks.

Official Title
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LIBERTY EXTENSION: An International Phase 3 Open-Label, Single-Arm, Long-Term Efficacy and Safety Extension Study to Evaluate Relugolix Co-Administered With Low-Dose Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

Conditions
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Heavy Menstrual Bleeding, Uterine Fibroid

Intervention / Treatment
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* Drug: Relugolix
* Drug: Estradiol/norethindrone acetate


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 1. Completed 24 weeks of study drug treatment and study participation in either parent study, MVT-601-3001 or MVT-601-3002 Key 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 (MVT-601-3001 or MVT-601-3002) Met a withdrawal criterion in the parent study (MVT-601-3001 or MVT-601-3002).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-Label Extension
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Relugolix plus E2/NETA<br>Relugolix co-administered with E2/NETA for 28 weeks. | Drug: Relugolix<br>* Relugolix 40-mg tablet administered orally once daily<br>* Other names: TAK-385;Drug: Estradiol/norethindrone acetate<br>* Capsule containing co-formulated tablet of E2 (1.0 mg) and NETA (0.5 mg) administered orally once daily<br>* Other names: Low-dose hormonal add-back;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate Based On Reduction In Menstrual Blood Loss (MBL) Volume At Week 52 | Defined as the proportion of women who achieve an MBL volume of < 80 milliliters (mL) and at least a 50% reduction from parent study Baseline to the last 35 days of treatment. MBL volume is measured using the alkaline hematin method. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Parent Study Baseline In MBL Volume At Week 52 | MBL volume is measured using the alkaline hematin method. | Parent Study Baseline, Week 52 | 
| Proportion Of Women Who Achieve Or Maintain Amenorrhea At Week 52 | Will be assessed using participant reporting at visit and MBL volume measured using the alkaline hematin method. | Week 52 | 
| Proportion Of Women With Hemoglobin Below The Lower Limit Of Normal At Parent Study Baseline Who Achieve An Increase Of At Least 1 Gram/Deciliter (g/dL) From Parent Study Baseline At Week 52 | Blood samples will be collected from participants for hemoglobin measurements. | Week 52 | 
| Proportion Of Women With A Hemoglobin ≤ 10.5 g/dL At Parent Study Baseline Who Achieve An Increase Of > 2 g/dL From Parent Study Baseline At Week 52 | Blood samples will be collected from participants for hemoglobin measurements. | Week 52 | 
| Change From Parent Study Baseline In Hemoglobin At Week 52 | Blood samples will be collected from participants for hemoglobin measurements. | Parent Study Baseline, Week 52 | 
| Change From Parent Study Baseline In The Uterine Fibroid Scale-Symptom Severity At Week 52 | Assessed using the Uterine Fibroid Symptom Health-Related Quality of Life (UFS-QoL) Questionnaire. | Parent Study Baseline, Week 52 | 
| Change From Parent Study Baseline In The UFS-QoL Subscales And Total Score At Week 52 | Assessed using the UFS-QoL Questionnaire. | Parent Study Baseline, Week 52 | 
| Change From Parent Study Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Scale Score At Week 52 | Assessed using the UFS-QoL Questionnaire. | Parent Study Baseline, Week 52 | 
| Change From Parent Study Baseline In Uterine Volume At Week 52 | Volume of the uterus will be measured by transvaginal or transabdominal ultrasound. | Parent Study Baseline, Week 52 | 
| Change From Parent Study Baseline In Uterine Fibroid Volume At Week 52 | Volume of the primary uterine fibroid will be measured by transvaginal or transabdominal ultrasound. | Parent Study Baseline, Week 52 | 
| Percent Change From Parent Study Baseline In Bone Mineral Density (BMD) At The Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52 | Assessed by dual-energy X-ray absorptiometry scan. | Parent Study Baseline, Week 52 | 
| Change From Parent Study Baseline In Pre-dose Serum E2 Concentrations At Week 52 | Blood samples will be collected from participants for E2 measurements. | Parent Study Baseline, Week 52 | 
| Change From Parent Study Baseline In European Quality Of Life Five Dimension Five Level At Week 52 |  | Parent Study Baseline, Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uterine Fibroid, Heavy Menstrual Bleeding, Menstrual Blood Volume