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

NCT ID: NCT03751124

Last Updated: 2024-06-25

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

229 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-16

Study Completion Date

2021-10-20

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Uterine Leiomyoma Uterine Fibroids

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized withdrawal following an open-label extension to a randomized controlled parent study
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Relugolix plus E2/NETA

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

Group Type EXPERIMENTAL

Relugolix

Intervention Type DRUG

Relugolix 40 mg tablet administered orally once daily

Estradiol/norethindrone acetate

Intervention Type DRUG

Capsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily

Placebo tablets and capsules

* 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.

Group Type PLACEBO_COMPARATOR

Placebo for relugolix

Intervention Type DRUG

Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor

Placebo for E2/NETA

Intervention Type DRUG

Placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor

Interventions

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Relugolix

Relugolix 40 mg tablet administered orally once daily

Intervention Type DRUG

Estradiol/norethindrone acetate

Capsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily

Intervention Type DRUG

Placebo for relugolix

Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor

Intervention Type DRUG

Placebo for E2/NETA

Placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor

Intervention Type DRUG

Other Intervention Names

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TAK-385 E2/NETA Low-dose hormonal add-back

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

51 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Myovant Sciences GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Birmingham

Birmingham, Alabama, United States

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Mesa

Mesa, Arizona, United States

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Tucson

Tucson, Arizona, United States

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Canoga Park

Canoga Park, California, United States

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Huntington Beach

Huntington Beach, California, United States

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La Mesa

La Mesa, California, United States

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Los Angeles

Los Angeles, California, United States

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Norwalk

Norwalk, California, United States

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San Diego

San Diego, California, United States

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Denver

Denver, Colorado, United States

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Lakewood

Lakewood, Colorado, United States

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Aventura

Aventura, Florida, United States

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Clearwater

Clearwater, Florida, United States

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Deland

DeLand, Florida, United States

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Ft. Lauderdale

Fort Lauderdale, Florida, United States

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Fort Myers

Fort Myers, Florida, United States

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Jacksonville

Jacksonville, Florida, United States

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Jupiter

Jupiter, Florida, United States

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Margate

Margate, Florida, United States

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Miami

Miami, Florida, United States

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Miami

Miami, Florida, United States

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Miami

Miami, Florida, United States

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Orlando

Orlando, Florida, United States

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Oviedo

Oviedo, Florida, United States

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Sarasota

Sarasota, Florida, United States

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Tampa

Tampa, Florida, United States

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United States, Florida

West Palm Beach, Florida, United States

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West Palm Beach

West Palm Beach, Florida, United States

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Weston

Weston, Florida, United States

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Atlanta

Atlanta, Georgia, United States

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Augusta

Augusta, Georgia, United States

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College Park

College Park, Georgia, United States

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Dacatur

Decatur, Georgia, United States

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Duluth

Duluth, Georgia, United States

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Norcross

Norcross, Georgia, United States

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Savannah

Savannah, Georgia, United States

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Smyrna

Smyrna, Georgia, United States

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Chicago

Chicago, Illinois, United States

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Oak brook

Oak Brook, Illinois, United States

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Shawnee

Shawnee Mission, Kansas, United States

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Covington

Covington, Louisiana, United States

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Marrero

Marrero, Louisiana, United States

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Metairie

Metairie, Louisiana, United States

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Baltimore

Baltimore, Maryland, United States

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Towson

Towson, Maryland, United States

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Canton

Canton, Michigan, United States

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Detroit

Detroit, Michigan, United States

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Las Vegas

Las Vegas, Nevada, United States

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Las Vegas

Las Vegas, Nevada, United States

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Lawrenceville

Lawrenceville, New Jersey, United States

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Williamsville

Williamsville, New York, United States

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Durham

Durham, North Carolina, United States

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Raleigh

Raleigh, North Carolina, United States

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Raleigh

Raleigh, North Carolina, United States

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Winston Salem

Winston-Salem, North Carolina, United States

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Cincinnati

Cincinnati, Ohio, United States

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Bluffton

Bluffton, South Carolina, United States

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Charleston

Charleston, South Carolina, United States

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Columbia

Columbia, South Carolina, United States

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Chattanooga

Chattanooga, Tennessee, United States

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Memphis

Memphis, Tennessee, United States

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Memphis

Memphis, Tennessee, United States

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Dallas

Dallas, Texas, United States

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Houston

Houston, Texas, United States

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Houston

Houston, Texas, United States

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Longview

Longview, Texas, United States

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San Antonio

San Antonio, Texas, United States

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San Antonio

San Antonio, Texas, United States

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Webster

Webster, Texas, United States

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Norfolk

Norfolk, Virginia, United States

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Richmond

Richmond, Virginia, United States

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Spokane

Spokane, Washington, United States

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Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

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São Bernardo do Campo

São Bernardo do Campo, São Paulo, Brazil

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Sao Paulo

São Paulo, São Paulo, Brazil

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Porto Alegre

Porto Alegre, , Brazil

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São Paulo

São Paulo, , Brazil

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Providencia

Providencia, , Chile

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San Ramon

San Ramón, , Chile

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Santiago

Santiago, , Chile

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České Budějovice

České Budějovice, , Czechia

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Olomouc

Olomouc, , Czechia

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Pisek

Písek, , Czechia

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Kecskemét

Kecskemét, Bács-Kiskun county, Hungary

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Debrecen

Debrecen, , Hungary

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Debrecen

Debrecen, , Hungary

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Gyula

Gyula, , Hungary

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Nyíregyháza

Nyíregyháza, , Hungary

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Szentes

Szentes, , Hungary

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Catanzaro

Catanzaro, , Italy

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Roma

Roma, , Italy

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SIENA

Siena, , Italy

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Torino

Torino, , Italy

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Szczecin

Szczecin, West Pomeranian Voivodeship, Poland

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Bialystok

Bialystok, , Poland

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Katowice

Katowice, , Poland

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Poznan

Poznan, , Poland

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Warszawa

Warsaw, , Poland

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Bloemfontein

Bloemfontein, Free State, South Africa

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Centurion

Centurion, Gauteng, South Africa

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Cape Town

Cape Town, Western Cape, South Africa

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Cape Town

Cape Town, Western Cape, South Africa

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Durban

Durban, , South Africa

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Roodepoort

Roodepoort, , South Africa

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Countries

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United States Brazil Chile Czechia Hungary Italy Poland South Africa

References

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Al-Hendy A, Venturella R, Arjona Ferreira JC, Li Y, Soulban G, Wagman RB, Lukes AS. LIBERTY randomized withdrawal study: relugolix combination therapy for heavy menstrual bleeding associated with uterine fibroids. Am J Obstet Gynecol. 2023 Dec;229(6):662.e1-662.e25. doi: 10.1016/j.ajog.2023.08.030. Epub 2023 Sep 2.

Reference Type DERIVED
PMID: 37666383 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-001368-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MVT-601-035

Identifier Type: -

Identifier Source: org_study_id

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