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

• ClinicalTrials.gov Identifier: NCT03412890
• Recruitment Status: Active, not recruiting
• First Posted: January 29, 2018
• Last Update Posted: September 10, 2019
• Sponsor: Myovant Sciences GmbH
• Information provided by (Responsible Party): Myovant Sciences GmbH

Study Description

Brief Summary:

The purpose of this study is to determine the long-term efficacy of Relugolix 40 mg once daily co-administered with low-dose estradiol and norethindrone acetate for up to 52 weeks, on heavy menstrual bleeding associated with uterine fibroids in patients who previously completed a 24-week treatment period in one of the parent studies (MVT-601-3001 or MVT-601-3002).

Condition or disease	Intervention/treatment	Phase
Heavy Menstrual Bleeding; Uterine Fibroid	Drug: Relugolix; Drug: Estradiol/norethindrone acetate	Phase 3

Detailed Description:

This study is an international phase 3 open-label, single-arm, long-term efficacy and safety extension study that will enroll eligible patients 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 patients will receive relugolix 40 mg once daily co-administered with low-dose estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for up to 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 estradiol/norethindrone acetate.

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. Patients 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 patient 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 600 participants
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open-Label Extension
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 19, 2017
• Estimated Primary Completion Date: February 28, 2020
• Estimated Study Completion Date: July 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Relugolix plus E2/NETA; Relugolix 40 mg co-administered with estradiol (1.0 mg) and norethindrone acetate (0.5 mg) for up to 28 weeks	Drug: Relugolix; Relugolix 40 mg tablet administered orally once daily; Other Name: TAK-385; Drug: Estradiol/norethindrone acetate; Capsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily; Other Name: E2/NETA, low-dose hormonal add-back

Outcome Measures

Primary Outcome Measures :

1. Responder rate based on reduction in menstrual blood loss (MBL) volume [ Time Frame: from Parent study Baseline up to last 35 days of treatment, anticipated to be up to 52 weeks ]
   Defined as the proportion of women who achieve a MBL volume of < 80 mL and a ≥ 50% reduction from parent study Baseline MBL volume over the last 35 days of treatment. MBL volume is measured using the alkaline hematin method.

Secondary Outcome Measures :

1. Time to MBL response [ Time Frame: up to 52 weeks ]
   Defined as the time to achieve a MBL volume of < 80 mL and a ≥ 50% reduction from parent study Baseline MBL volume as measured by the alkaline hematin method.
2. Change in MBL volume [ Time Frame: from parent study Baseline up to Week 52 ]
   MBL volume is measured using the alkaline hematin method.
3. Proportion of women with suppression of bleeding [ Time Frame: from parent study Baseline up to last 35 days of treatment, anticipated to be up to 52 weeks ]
   Will be assessed using patient daily diary and MBL volume measured using the alkaline hematin method.
4. Change in hemoglobin concentration [ Time Frame: from parent study Baseline up to Week 52 ]
   Blood samples will be collected from participants for hemoglobin measurements.
5. Change in uterine volume [ Time Frame: from parent study Baseline up to Week 52 ]
   Volume of the uterus will be measured by transvaginal or transabdominal ultrasound.
6. Change in primary fibroid volume [ Time Frame: from parent study Baseline up to Week 52 ]
   Volume of the primary fibroid will be measured by transvaginal or transabdominal ultrasound.
7. Change in impact on quality of life [ Time Frame: from parent study Baseline up to Week 52 ]
   Assessed using the Uterine Fibroid Symptom Health-Related Quality of Life Questionnaire (UFS-QOL).
8. Bone Mineral Density (BMD) [ Time Frame: from parent study Baseline up to Week 52 ]
   Assessed by dual-energy X-ray absorptiometry (DXA) scan.
9. The number and percentage of participants with adverse events (AE) as a measure of safety and tolerability [ Time Frame: up to 52 weeks ]
   Assessed by frequency and severity of AEs and serious AEs.
10. Serum estradiol concentrations [ Time Frame: up to 52 weeks ]
    Blood samples will be collected from participants for estradiol measurements.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Completed 24 weeks of study drug treatment and study participation in either MVT‑601‑3001 or MVT‑601‑3002

Key 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 (MVT‑601‑3001 or MVT‑601‑3002)
2. Met a withdrawal criterion in the parent study (MVT‑601‑3001 or MVT‑601‑3002).

Contacts and Locations

  Show 155 Study Locations

Sponsors and Collaborators

Myovant Sciences GmbH

Investigators

• Study Director: Myovant Medical Monitor, MD; Myovant Sciences

More Information

• Responsible Party: Myovant Sciences GmbH
• ClinicalTrials.gov Identifier: NCT03412890 History of Changes
• Other Study ID Numbers: MVT-601-3003; 2017-003310-74 ( EudraCT Number )
• First Posted: January 29, 2018
• Last Update Posted: September 10, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leiomyoma; Myofibroma; Menorrhagia; Hemorrhage; Pathologic Processes; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Connective Tissue Diseases; Uterine Hemorrhage; Uterine Diseases; Genital Diseases, Female; Menstruation Disturbances; Estradiol 3-benzoate; Estradiol 17 beta-cypionate; Norethindrone; Norethindrone Acetate; Estradiol; Polyestradiol phosphate; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral