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

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

The purpose of this study was to determine the long-term efficacy and safety of relugolix 40 milligrams (mg) once daily co-administered with 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 pivotal studies (MVT-601-3001 or MVT-601-3002).

Study Overview

• Status: Completed
• Conditions: Uterine Fibroid; Heavy Menstrual Bleeding
• Intervention / Treatment: Drug: Relugolix; Drug: Estradiol/norethindrone acetate

Detailed Description

This study is an international phase 3 open-label, single-arm, long-term efficacy and safety extension study that enrolled eligible participants who have completed their participation in one of the phase 3 randomized, double-blind, placebo-controlled pivotal studies, MVT-601-3001 (LIBERTY 1 - NCT03049735) or MVT-601-3002 (LIBERTY 2 - NCT 03103087). All participants received relugolix 40 mg orally once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 28 weeks.

Approximately 600 women with heavy menstrual bleeding associated with uterine fibroids were to be enrolled, after having completed a 24-week treatment period in one of the pivotal studies. The objectives of the study were to evaluate long-term efficacy and safety through up to 52 weeks of treatment (including treatment during the pivotal study) of relugolix co-administered with E2/NETA.

Screening and baseline procedures were to be done at the same visit for this extension study (referred to as the "Week 24/Baseline Visit"), which coincided with the Week 24 Visit from the pivotal study and was to be defined as the date of completion of the last Week 24 procedure in the pivotal study. Participants will have received their last dose of study drug in the pivotal study on the day prior to the Week 24/Baseline Visit and were to receive their first dose of study drug for this extension study in the clinic after the participant was determined to be eligible for this extension study and provided informed consent to participate. The administration of the first dose of study drug for MVT-601-3003 was to define enrollment into this study. Study participants were to then take the open-label study treatment orally once daily for 28 weeks.

• Study Type: Interventional
• Enrollment (Actual): 477
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Brussels
  • Jette, Belgium, 1090
    • Jette
  • Hainaut
    • La Louvière, Hainaut, Belgium, 7100
      • La Louvière
  • Oost-vlaanderen
    • Gent, Oost-vlaanderen, Belgium, 9000
      • Gent
• Brazil
  • Botucatu, Brazil, 18618-686
    • Botucatu
  • Porto Alegre, Brazil, 90510-040
    • Porto Alegre
  • Porto Alegre, Brazil, 90035-903
    • Porto Alegre
  • SAO Paulo
    • Santo André, SAO Paulo, Brazil, 09190-510
      • Santo André
  • Santo Andre
    • Santo André, Santo Andre, Brazil, 09190-510
      • Santo André
  • Sao Paulo
    • São Bernardo Do Campo, Sao Paulo, Brazil, 09715-090
      • São Bernardo do Campo
    • São Paulo, Sao Paulo, Brazil, 04266-010
      • São Paulo
    • São Paulo, Sao Paulo, Brazil, 01317-000
      • São Paulo
• Chile
  • Providencia, Chile, 7510186
    • Providencia
  • San Ramón, Chile, 8880465
    • San Ramon
  • Santiago, Chile, 8360160
    • Santiago
  • Santiago, Chile, 8320165
    • Region Metropolitana
• Czechia
  • Jihlava, Czechia, 586 33
    • Jihlava
  • Olomouc, Czechia, 772 00
    • Olomouc
  • Písek, Czechia, 39701
    • Pisek
  • České Budějovice, Czechia, 370 01
    • České Budějovice
• Hungary
  • Debrecen, Hungary, 4025
    • Debrecen
  • Szentes, Hungary, 6600
    • Szentes
  • Bacs-kiskun
    • Kecskemét, Bacs-kiskun, Hungary, 6000
      • Kecskemét
  • Bekes
    • Gyula, Bekes, Hungary, 5700
      • Gyula
  • Hajdu-bihar
    • Debrecen, Hajdu-bihar, Hungary, 4024
      • Debrecen
  • Szabolcs-Szatmar-Bereg
    • Nyíregyháza, Szabolcs-Szatmar-Bereg, Hungary, 4400
      • Nyíregyháza
• Italy
  • Catanzaro, Italy, 88100
    • Catanzaro
  • Firenze, Italy, 50134
    • Firenze
  • Roma, Italy, 00168
    • Roma
  • Siena, Italy, 53100
    • Siena
  • Torino, Italy, 10126
    • Torino
• Poland
  • Białystok, Poland, 15-464
    • Bialystok
  • Lodzkie
    • Lódz, Lodzkie, Poland, 90-602
      • Lodz
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-632
      • Lublin
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-201
      • Warszawa
  • Slaskie
    • Katowice, Slaskie, Poland, 40-123
      • Katowice
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-192
      • Poznan
    • Skórzewo, Wielkopolskie, Poland, 60-185
      • Skórzewo
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 71-270
      • Szczecin
• South Africa
  • Bloemfontein, South Africa, 9301
    • Bloemfontein
  • Cape Town, South Africa, 7405
    • Cape Town
  • Cape Town, South Africa, 7500
    • Cape Town
  • Port Elizabeth, South Africa, 6001
    • Port Elizabeth
  • Gauteng
    • Centurion, Gauteng, South Africa, 0157
      • Centurion
    • Roodepoort, Gauteng, South Africa, 1724
      • Roodepoort
  • Kwazulu-natal
    • Durban, Kwazulu-natal, South Africa, 4001
      • Durban
• United States
  • Alabama
    • Andalusia, Alabama, United States, 36420
      • Andalusia
    • Birmingham, Alabama, United States, 35205
      • Birmingham
    • Mobile, Alabama, United States, 36608
      • Mobile
  • Arizona
    • Mesa, Arizona, United States, 85209
      • Mesa
    • Tucson, Arizona, United States, 85712
      • Tucson
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Little Rock
  • California
    • Canoga Park, California, United States, 91303
      • Canoga Park
    • Huntington Beach, California, United States, 92647
      • Huntington Beach
    • La Mesa, California, United States, 91942
      • La Mesa
    • Long Beach, California, United States, 90806
      • Long Beach
    • Los Angeles, California, United States, 90036
      • Los Angeles
    • Los Angeles, California, United States, 90057
      • Los Angeles
    • Norwalk, California, United States, 90650
      • Norwalk
    • Panorama City, California, United States, 91402
      • Panorama
    • San Diego, California, United States, 92111
      • San Diego
    • San Diego, California, United States, 92108
      • San Diego
  • Colorado
    • Denver, Colorado, United States, 80209
      • Denver
    • Lakewood, Colorado, United States, 80228
      • Lakewood
  • District of Columbia
    • Washington, District of Columbia, United States, 20036
      • Washington
  • Florida
    • Aventura, Florida, United States, 33180
      • Aventura
    • Clearwater, Florida, United States, 33759
      • Clearwater
    • DeLand, Florida, United States, 32720
      • Deland
    • Fort Lauderdale, Florida, United States, 33316
      • Ft. Lauderdale
    • Fort Myers, Florida, United States, 33912
      • Fort Myers
    • Hialeah, Florida, United States, 33016
      • Hialeah
    • Jacksonville, Florida, United States, 32207
      • Jacksonville
    • Jupiter, Florida, United States, 33458
      • Jupiter
    • Loxahatchee Groves, Florida, United States, 33470
      • Loxahatchee
    • Margate, Florida, United States, 33063
      • Margate
    • Miami, Florida, United States, 33126
      • Miami
    • Miami, Florida, United States, 33155
      • Miami
    • Miami, Florida, United States, 33165
      • Miami
    • New Port Richey, Florida, United States, 34652
      • New Port Richey
    • Orlando, Florida, United States, 32808
      • Orlando
    • Oviedo, Florida, United States, 32765
      • Oviedo
    • Palm Harbor, Florida, United States, 34684
      • Palm Harbor
    • Saint Cloud, Florida, United States, 34769
      • Saint Cloud
    • Sarasota, Florida, United States, 34239
      • Sarasota
    • Tampa, Florida, United States, 33606
      • Tampa
    • Tampa, Florida, United States, 33613
      • Tampa
    • West Palm Beach, Florida, United States, 33409
      • West Palm Beach
    • Weston, Florida, United States, 33327
      • Weston
  • Georgia
    • Atlanta, Georgia, United States, 30363
      • Atlanta
    • Atlanta, Georgia, United States, 30342
      • Atlanta
    • Augusta, Georgia, United States, 30904
      • Augusta
    • College Park, Georgia, United States, 30349
      • College Park
    • Decatur, Georgia, United States, 30034
      • Decatur
    • Duluth, Georgia, United States, 30097
      • Duluth
    • Norcross, Georgia, United States, 30093
      • Norcross
    • Savannah, Georgia, United States, 31406
      • Savannah
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Chicago
    • Naperville, Illinois, United States, 60540
      • Naperville
    • Oakbrook Terrace, Illinois, United States, 60523
      • Oakbrook
  • Kansas
    • Shawnee Mission, Kansas, United States, 66218
      • Shawnee
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Covington
    • Marrero, Louisiana, United States, 70072
      • Marrero
    • Metairie, Louisiana, United States, 70001
      • Metairie
    • Metairie, Louisiana, United States, 70006
      • Metairie
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Baltimore
    • Towson, Maryland, United States, 21204
      • Towson
  • Michigan
    • Canton, Michigan, United States, 48187
      • Canton
    • Detroit, Michigan, United States, 48201
      • Detroit
    • Saginaw, Michigan, United States, 48604
      • Saginaw
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Lincoln
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Las Vegas
    • Las Vegas, Nevada, United States, 89128
      • Las Vegas
    • Las Vegas, Nevada, United States, 89109
      • Las Vegas
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Lawrenceville
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque
  • New York
    • Brooklyn, New York, United States, 11201
      • Brooklyn
    • New York, New York, United States, 10022
      • New York
    • Williamsville, New York, United States, 14221
      • Williamsville
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Durham
    • Raleigh, North Carolina, United States, 27612
      • Raleigh
    • Raleigh, North Carolina, United States, 27607
      • Raleigh
    • Winston-Salem, North Carolina, United States, 27103
      • Winston-Salem
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Cincinnati
    • Cincinnati, Ohio, United States, 45212
      • Cincinnati
    • Columbus, Ohio, United States, 43231
      • Columbus
    • Englewood, Ohio, United States, 45322
      • Englewood
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia
  • South Carolina
    • Bluffton, South Carolina, United States, 29910
      • Bluffton
    • Charleston, South Carolina, United States, 29406
      • Charleston
    • Columbia, South Carolina, United States, 29201
      • Columbia
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga
    • Memphis, Tennessee, United States, 38120
      • Memphis
    • Memphis, Tennessee, United States, 38119
      • Memphis
  • Texas
    • Beaumont, Texas, United States, 77702
      • Beaumont
    • Dallas, Texas, United States, 75231
      • Dallas
    • Fort Worth, Texas, United States, 76104
      • Fort Worth
    • Houston, Texas, United States, 77030
      • Houston
    • Houston, Texas, United States, 77054
      • Houston
    • Houston, Texas, United States, 77074
      • Houston
    • Longview, Texas, United States, 75605
      • Longview
    • San Antonio, Texas, United States, 78229
      • San Antonio
    • San Antonio, Texas, United States, 78258
      • San Antonio
    • Sugar Land, Texas, United States, 77479
      • Sugar Land
    • Webster, Texas, United States, 77598
      • Webster
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Salt Lake City
    • Salt Lake City, Utah, United States, 84107
      • Salt Lake City
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Norfolk
    • Norfolk, Virginia, United States, 23507
      • Norfolk
    • Richmond, Virginia, United States, 23225
      • Richmond
  • Washington
    • Spokane, Washington, United States, 99207
      • Spokane

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Completed 24 weeks of study drug treatment and study participation in either pivotal study, 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 pivotal study (MVT-601-3001 or MVT-601-3002)
2. Met a withdrawal criterion in the pivotal study (MVT-601-3001 or MVT-601-3002).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relugolix plus E2/NETA; Relugolix co-administered with E2/NETA for 28 weeks.	Drug: Relugolix; Relugolix 40-mg tablet administered orally once daily; Other Names: TAK-385; MVT-601; Drug: Estradiol/norethindrone acetate; Capsule containing co-formulated tablet of E2 (1 mg) and NETA (0.5 mg) administered orally once daily; Other Names: E2/NETA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Of Participants Who Achieved Or Maintained An MBL Volume Of <80 Milliliters (mL) And At Least A 50% Reduction From Baseline MBL Volume At Week 52/End Of Treatment	A responder was a participant who had MBL volume of < 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment (up to Week 52). All returned feminine products collected at each clinical visit were analyzed by the alkaline hematin method to obtain the MBL volume. MBL volume was measured over the Week 52/early termination feminine product collection interval (up to 35 days prior to the last dose of treatment). The percentage of participants who were responders are presented.	Week 52/End of Treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Pivotal Study Baseline In MBL Volume At Week 52	MBL volume was measured using the alkaline hematin method, which involves chemically measuring the blood content of used feminine products. 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 least squares (LS) mean was derived for each treatment group using a mixed-effects model with repeated measure with visit, region, and Baseline MBL as fixed effects.	Week 52
Percentage Of Participants Who Achieved Or Maintained Amenorrhea Over The Last 35 Days Of Treatment	Amenorrhea was defined as meeting 1 of the following criteria for 2 consecutive visits: No feminine product returned due to reported amenorrhea;; No feminine product returned due to reports of spotting/negligible bleeding coupled with other data (participant's paper diary) indicating infrequent non-cyclic bleeding/spotting; and; Feminine product collection with a negligible observed MBL volume coupled with data (participant's paper diary) indicating infrequent non-cyclic bleeding/spotting.	Week 24 up to last 35 days of treatment (up to Week 52)
Percentage Of Participants With A Hemoglobin Level ≤10.5 Gram/Deciliter (g/dL) At Pivotal Study Baseline Who Achieved An Increase Of >2 g/dL From Pivotal Study Baseline At Week 52	Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin ≤10.5 g/dL at pivotal study Baseline and reported at Week 52.	Week 52
Number Of Participants With Hemoglobin Increase Of ≥1 g/dL From Pivotal Study Baseline At Week 52 Among Those With A Hemoglobin Concentration Below Lower Limit Of Normal At Pivotal Baseline	Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin concentration below the lower limit of normal (11.6 g/dL) at pivotal study Baseline and reported at Week 52.	Week 52
Change From Pivotal Study Baseline In Hemoglobin Concentration At Week 52	Blood samples were collected from participants for hemoglobin measurements. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.	Week 52
Change From Pivotal Study Baseline In The UFS-QoL Symptom Severity Scale At Week 52	Transformed score ranges from 0 to 100 based on Likert scale (none of time, a little of time, some of the time, most of the time, and all of the time). Lower score indicates less distress and higher score indicates greater distress. A negative change from baseline indicates improvement. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.	Week 52
Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At Week 52	Assessed using the UFS-QoL questionnaire. The UFS-QoL subscale scores include items related to uterine fibroid-associated limitations/impairment in activities, revised activities, concern, energy/mood, control, self-consciousness, and sexual function. The scores were transformed to normalized scores. Transformed score ranges from 0 to 100. Higher scores are indicative of better health-related quality of life (high = good). The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.	Week 52
Change From Pivotal Study Baseline In The UFS-QoL Score By Health-Related Quality of Life Total Score At Week 52	Assessed using the UFS-QoL Questionnaire. The UFS-QoL total score was the sum of the subscales (concern, activities, revised activities, energy/mood, control, self-conscious, and sexual function). The raw scores were transformed to normalized scores. Transformed score ranges from 0 to 100. Higher scores are indicative of better health-related quality of life (high = good). The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.	Week 52
Change From Pivotal Study Baseline In The Uterine Fibroid Symptom Health-Related Quality of Life (UFS-QoL) Bleeding And Pelvic Discomfort (BPD) Scale At Week 52	The BPD scale has been derived from the UFS-QoL symptom severity scale. The scale consists of the following 3 symptoms proximal to uterine fibroids that are experienced by most participants: heavy bleeding during the menstrual period (Question 1), passing blood clots during the menstrual period (Question 2), and feeling tightness or pressure in the pelvic area (Question 5). Raw scores were transformed to a normalized score, with a range of possible scores from 0 to 100 (none of time, a little of time, some of the time, most of the time, and all of the time), where higher scores values are indicative of greater distress and lower scores are indicative of minimal distress. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.	Week 52
Change From Pivotal Study Baseline In Uterine Volume At Week 52	Volume of the uterus was measured by transvaginal or transabdominal ultrasound. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.	Week 52
Change From Pivotal Study Baseline In Uterine Fibroid Volume At Week 52	Volume of the primary uterine fibroid was measured by transvaginal or transabdominal ultrasound. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.	Week 52
Percent Change From Pivotal 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 (DXA) scan at the lumbar spine (L1-L4), total hip, and femoral neck at pivotal study Baseline and at Week 52. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.	Week 52
Change From Pivotal Study Baseline In Predose Serum E2 Concentrations At Week 52	Blood samples were collected from participants at predose for E2 measurements. These were analyzed at a central laboratory.	Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52	The EQ-5D-5L scale is a standardized instrument for use as a measure of health outcomes. Mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were each assessed on 5-point categorical scales of no problems to unable to complete specified activity, or no pain/discomfort to extreme pain/discomfort, or not anxious/depressed to extremely anxious/depressed. The change from baseline is summarized by amount of improvement (1-4 categories), amount of deterioration (1-4 categories), or no change.	Week 52

Collaborators and Investigators

• Sponsor: Myovant Sciences GmbH
• Investigators: Study Director: Myovant Medical Monitor, Myovant Sciences

Publications and helpful links

General Publications

• Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, McKain L, Li Y, Wagman RB, Stewart EA. Long-term Relugolix Combination Therapy for Symptomatic Uterine Leiomyomas. Obstet Gynecol. 2022 Dec 1;140(6):920-930. doi: 10.1097/AOG.0000000000004988. Epub 2022 Nov 2.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2017
• Primary Completion (Actual): January 21, 2020
• Study Completion (Actual): January 13, 2021

Study Registration Dates

• First Submitted: January 19, 2018
• First Submitted That Met QC Criteria: January 19, 2018
• First Posted (Actual): January 29, 2018

Study Record Updates

• Last Update Posted (Actual): May 9, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Uterine Fibroid; Heavy Menstrual Bleeding; Menstrual Blood Volume
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Uterine Diseases; Connective Tissue Diseases; Neoplasms, Connective Tissue; Menstruation Disturbances; Neoplasms, Muscle Tissue; Uterine Hemorrhage; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Hemorrhage; Leiomyoma; Myofibroma; Menorrhagia; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Androgen Antagonists; Estradiol; Norethindrone; Norethindrone Acetate; Relugolix
• Other Study ID Numbers: MVT-601-3003; 2017-003310-74 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No