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

Uterine Fibroid Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03412890
• Other study ID #: MVT-601-3003
• Secondary ID: 2017-003310-74
• Status: Completed
• Phase: Phase 3
• Start date: October 19, 2017
• Est. completion date: January 13, 2021

Study information

• Verified date: April 2024
• Source: Myovant Sciences GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 477
• Est. completion date: January 13, 2021
• Est. primary completion date: January 21, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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).

Related Conditions & MeSH terms

• Heavy Menstrual Bleeding
• Hemorrhage
• Leiomyoma
• Menorrhagia
• Uterine Fibroid

Intervention

Drug:
• Relugolix
Relugolix 40-mg tablet administered orally once daily
• Estradiol/norethindrone acetate
Capsule containing co-formulated tablet of E2 (1 mg) and NETA (0.5 mg) administered orally once daily

Locations

Country	Name	City	State
Belgium	Brussels	Brussels
Belgium	Gent	Gent	Oost-vlaanderen
Belgium	Jette	Jette
Belgium	La Louvière	La Louvière	Hainaut
Brazil	Botucatu	Botucatu
Brazil	Porto Alegre	Porto Alegre
Brazil	Porto Alegre	Porto Alegre
Brazil	Santo Andre	Santo André	Santo Andre
Brazil	Santo André	Santo André	SAO Paulo
Brazil	São Bernardo Do Campo	São Bernardo Do Campo	Sao Paulo
Brazil	Sao Paulo	São Paulo	Sao Paulo
Brazil	Sao Paulo	São Paulo	Sao Paulo
Chile	Providencia	Providencia
Chile	San Ramon	San Ramón
Chile	Region Metropolitana	Santiago
Chile	Santiago	Santiago
Czechia	Ceské Budejovice	Ceské Budejovice
Czechia	Jihlava	Jihlava
Czechia	Olomouc	Olomouc
Czechia	Pisek	Písek
Hungary	Debrecen	Debrecen	Hajdu-bihar
Hungary	Debrecen	Debrecen
Hungary	Gyula	Gyula	Bekes
Hungary	Kecskemét	Kecskemét	Bacs-kiskun
Hungary	Nyíregyháza	Nyíregyháza	Szabolcs-Szatmar-Bereg
Hungary	Szentes	Szentes
Italy	Catanzaro	Catanzaro
Italy	Firenze	Firenze
Italy	Roma	Roma
Italy	Siena	Siena
Italy	Torino	Torino
Poland	Bialystok	Bialystok
Poland	Katowice	Katowice	Slaskie
Poland	Lódz	Lódz	Lodzkie
Poland	Lublin	Lublin	Lubelskie
Poland	Poznan	Poznan	Wielkopolskie
Poland	Skórzewo	Skórzewo	Wielkopolskie
Poland	Szczecin	Szczecin	Zachodniopomorskie
Poland	Warszawa	Warszawa	Mazowieckie
South Africa	Bloemfontein	Bloemfontein
South Africa	Cape Town	Cape Town
South Africa	Cape Town	Cape Town
South Africa	Centurion	Centurion	Gauteng
South Africa	Durban	Durban	Kwazulu-natal
South Africa	Port Elizabeth	Port Elizabeth
South Africa	Roodepoort	Roodepoort	Gauteng
United States	Albuquerque	Albuquerque	New Mexico
United States	Andalusia	Andalusia	Alabama
United States	Atlanta	Atlanta	Georgia
United States	Atlanta	Atlanta	Georgia
United States	Augusta	Augusta	Georgia
United States	Aventura	Aventura	Florida
United States	Baltimore	Baltimore	Maryland
United States	Beaumont	Beaumont	Texas
United States	Birmingham	Birmingham	Alabama
United States	Bluffton	Bluffton	South Carolina
United States	Brooklyn	Brooklyn	New York
United States	Canoga Park	Canoga Park	California
United States	Canton	Canton	Michigan
United States	Charleston	Charleston	South Carolina
United States	Chattanooga	Chattanooga	Tennessee
United States	Chicago	Chicago	Illinois
United States	Cincinnati	Cincinnati	Ohio
United States	Cincinnati	Cincinnati	Ohio
United States	Clearwater	Clearwater	Florida
United States	College Park	College Park	Georgia
United States	Columbia	Columbia	South Carolina
United States	Columbus	Columbus	Ohio
United States	Covington	Covington	Louisiana
United States	Dallas	Dallas	Texas
United States	Decatur	Decatur	Georgia
United States	DeLand	DeLand	Florida
United States	Denver	Denver	Colorado
United States	Detroit	Detroit	Michigan
United States	Duluth	Duluth	Georgia
United States	Durham	Durham	North Carolina
United States	Englewood	Englewood	Ohio
United States	Ft. Lauderdale	Fort Lauderdale	Florida
United States	Fort Myers	Fort Myers	Florida
United States	Fort Worth	Fort Worth	Texas
United States	Hialeah	Hialeah	Florida
United States	Houston	Houston	Texas
United States	Houston	Houston	Texas
United States	Houston	Houston	Texas
United States	Huntington Beach	Huntington Beach	California
United States	Jacksonville	Jacksonville	Florida
United States	Jupiter	Jupiter	Florida
United States	La Mesa	La Mesa	California
United States	Lakewood	Lakewood	Colorado
United States	Las Vegas	Las Vegas	Nevada
United States	Las Vegas	Las Vegas	Nevada
United States	Las Vegas	Las Vegas	Nevada
United States	Lawrenceville	Lawrenceville	New Jersey
United States	Lincoln	Lincoln	Nebraska
United States	Little Rock	Little Rock	Arkansas
United States	Long Beach	Long Beach	California
United States	Longview	Longview	Texas
United States	Los Angeles	Los Angeles	California
United States	Los Angeles	Los Angeles	California
United States	Loxahatchee	Loxahatchee Groves	Florida
United States	Margate	Margate	Florida
United States	Marrero	Marrero	Louisiana
United States	Memphis	Memphis	Tennessee
United States	Memphis	Memphis	Tennessee
United States	Mesa	Mesa	Arizona
United States	Metairie	Metairie	Louisiana
United States	Metairie	Metairie	Louisiana
United States	Miami	Miami	Florida
United States	Miami	Miami	Florida
United States	Miami	Miami	Florida
United States	Mobile	Mobile	Alabama
United States	Naperville	Naperville	Illinois
United States	New Port Richey	New Port Richey	Florida
United States	New York	New York	New York
United States	Norcross	Norcross	Georgia
United States	Norfolk	Norfolk	Virginia
United States	Norfolk	Norfolk	Virginia
United States	Norwalk	Norwalk	California
United States	Oakbrook	Oakbrook Terrace	Illinois
United States	Orlando	Orlando	Florida
United States	Oviedo	Oviedo	Florida
United States	Palm Harbor	Palm Harbor	Florida
United States	Panorama	Panorama City	California
United States	Philadelphia	Philadelphia	Pennsylvania
United States	Raleigh	Raleigh	North Carolina
United States	Raleigh	Raleigh	North Carolina
United States	Richmond	Richmond	Virginia
United States	Saginaw	Saginaw	Michigan
United States	Saint Cloud	Saint Cloud	Florida
United States	Salt Lake City	Salt Lake City	Utah
United States	Salt Lake City	Salt Lake City	Utah
United States	San Antonio	San Antonio	Texas
United States	San Antonio	San Antonio	Texas
United States	San Diego	San Diego	California
United States	San Diego	San Diego	California
United States	Sarasota	Sarasota	Florida
United States	Savannah	Savannah	Georgia
United States	Shawnee	Shawnee Mission	Kansas
United States	Spokane	Spokane	Washington
United States	Sugar Land	Sugar Land	Texas
United States	Tampa	Tampa	Florida
United States	Tampa	Tampa	Florida
United States	Towson	Towson	Maryland
United States	Tucson	Tucson	Arizona
United States	Washington	Washington	District of Columbia
United States	Webster	Webster	Texas
United States	West Palm Beach	West Palm Beach	Florida
United States	Weston	Weston	Florida
United States	Williamsville	Williamsville	New York
United States	Winston-Salem	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Myovant Sciences GmbH

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Chile,  Czechia,  Hungary,  Italy,  Poland,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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