NCT03751124

Brief Summary

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
229

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Oct 2018

Typical duration for phase_3

Geographic Reach
8 countries

104 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 16, 2018

Completed
28 days until next milestone

First Submitted

Initial submission to the registry

November 13, 2018

Completed
10 days until next milestone

First Posted

Study publicly available on registry

November 23, 2018

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 19, 2021

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 20, 2021

Completed
2.7 years until next milestone

Results Posted

Study results publicly available

June 25, 2024

Completed
Last Updated

June 25, 2024

Status Verified

May 1, 2024

Enrollment Period

2.3 years

First QC Date

November 13, 2018

Results QC Date

August 26, 2022

Last Update Submit

May 31, 2024

Conditions

Keywords

Heavy menstrual bleedingMenorrhagiaUterine FibroidsUterine Leiomyoma

Outcome Measures

Primary Outcomes (1)

  • Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period

    MBL volume is measured using the alkaline hematin method. The method involves pummeling used feminine products in a 5% sodium hydroxide solution, which leads to the conversion of hemoglobin to alkaline hematin. 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 sustained responder rate was calculated as the Kaplan-Meier estimate of the cumulative probability of MBL volume \< 80 mL through Week 76 using the Kaplan-Meier method.

    Week 52/Baseline up to Week 76

Secondary Outcomes (47)

  • Time To MBL Volume ≥80 mL During The Randomized Treatment Period

    From Week 52/Baseline through Week 104

  • Percentage Of Participants Who Maintained MBL Volume Of <80 mL At Week 104 During The Randomized Treatment Period

    Week 52/Baseline up to Week 104

  • Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 76 During The Randomized Treatment Period

    Week 76

  • Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period

    Week 52/Baseline to Week 76

  • Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period

    Week 52/Baseline to Week 104

  • +42 more secondary outcomes

Study Arms (2)

Relugolix plus E2/NETA

EXPERIMENTAL

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

Drug: RelugolixDrug: Estradiol/norethindrone acetate

Placebo tablets and capsules

PLACEBO COMPARATOR

* 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.

Drug: Placebo for relugolixDrug: Placebo for E2/NETA

Interventions

Relugolix 40 mg tablet administered orally once daily

Also known as: TAK-385
Relugolix plus E2/NETA

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

Also known as: E2/NETA, Low-dose hormonal add-back
Relugolix plus E2/NETA

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

Placebo tablets and capsules

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

Placebo tablets and capsules

Eligibility Criteria

Age18 Years - 51 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Completed the open-label extension study (MVT-601-3003).
  • 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.
  • Is not expected to undergo gynecological surgery or ablation procedures for uterine fibroids within the study period

You may not qualify if:

  • 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.
  • Has a weight that exceeds the weight limit of the dual-energy x-ray absorptiometry (DXA) scanner
  • Has developed any contraindication to treatment with estradiol or norethindrone acetate
  • Is currently pregnant or lactating, or intends to become pregnant during the study period
  • Met a withdrawal criterion in the open-label extension (OLE) study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (104)

Birmingham

Birmingham, Alabama, 35205, United States

Location

Mesa

Mesa, Arizona, 85209, United States

Location

Tucson

Tucson, Arizona, 85712, United States

Location

Canoga Park

Canoga Park, California, 91303, United States

Location

Huntington Beach

Huntington Beach, California, 92647, United States

Location

La Mesa

La Mesa, California, 91942, United States

Location

Los Angeles

Los Angeles, California, 90057, United States

Location

Norwalk

Norwalk, California, 90650, United States

Location

San Diego

San Diego, California, 92111, United States

Location

Denver

Denver, Colorado, 80209, United States

Location

Lakewood

Lakewood, Colorado, 80228, United States

Location

Aventura

Aventura, Florida, 33180, United States

Location

Clearwater

Clearwater, Florida, 33759, United States

Location

Deland

DeLand, Florida, 32720, United States

Location

Ft. Lauderdale

Fort Lauderdale, Florida, 33316, United States

Location

Fort Myers

Fort Myers, Florida, 33912, United States

Location

Jacksonville

Jacksonville, Florida, 32207, United States

Location

Jupiter

Jupiter, Florida, 33458, United States

Location

Margate

Margate, Florida, 33063, United States

Location

Miami

Miami, Florida, 33126, United States

Location

Miami

Miami, Florida, 33155, United States

Location

Miami

Miami, Florida, 33165, United States

Location

Orlando

Orlando, Florida, 33759, United States

Location

Oviedo

Oviedo, Florida, 32765, United States

Location

Sarasota

Sarasota, Florida, 34239, United States

Location

Tampa

Tampa, Florida, 33613, United States

Location

United States, Florida

West Palm Beach, Florida, 33409, United States

Location

West Palm Beach

West Palm Beach, Florida, 33409, United States

Location

Weston

Weston, Florida, 33327, United States

Location

Atlanta

Atlanta, Georgia, 30342, United States

Location

Augusta

Augusta, Georgia, 30912, United States

Location

College Park

College Park, Georgia, 30349, United States

Location

Dacatur

Decatur, Georgia, 30034, United States

Location

Duluth

Duluth, Georgia, 30097, United States

Location

Norcross

Norcross, Georgia, 30093, United States

Location

Savannah

Savannah, Georgia, 31406, United States

Location

Smyrna

Smyrna, Georgia, 30080, United States

Location

Chicago

Chicago, Illinois, 60611, United States

Location

Oak brook

Oak Brook, Illinois, 60523, United States

Location

Shawnee

Shawnee Mission, Kansas, 66218, United States

Location

Covington

Covington, Louisiana, 70433, United States

Location

Marrero

Marrero, Louisiana, 70072, United States

Location

Metairie

Metairie, Louisiana, 70006, United States

Location

Baltimore

Baltimore, Maryland, 21208, United States

Location

Towson

Towson, Maryland, 21204, United States

Location

Canton

Canton, Michigan, 48187, United States

Location

Detroit

Detroit, Michigan, 48201, United States

Location

Las Vegas

Las Vegas, Nevada, 89109, United States

Location

Las Vegas

Las Vegas, Nevada, 89128, United States

Location

Lawrenceville

Lawrenceville, New Jersey, 08648, United States

Location

Williamsville

Williamsville, New York, 14221, United States

Location

Durham

Durham, North Carolina, 27713, United States

Location

Raleigh

Raleigh, North Carolina, 27607, United States

Location

Raleigh

Raleigh, North Carolina, 27612, United States

Location

Winston Salem

Winston-Salem, North Carolina, 27103, United States

Location

Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Bluffton

Bluffton, South Carolina, 29910, United States

Location

Charleston

Charleston, South Carolina, 29406, United States

Location

Columbia

Columbia, South Carolina, 29201, United States

Location

Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Memphis

Memphis, Tennessee, 38119, United States

Location

Memphis

Memphis, Tennessee, 38120, United States

Location

Dallas

Dallas, Texas, 75231, United States

Location

Houston

Houston, Texas, 77030, United States

Location

Houston

Houston, Texas, 77054, United States

Location

Longview

Longview, Texas, 75605, United States

Location

San Antonio

San Antonio, Texas, 78229, United States

Location

San Antonio

San Antonio, Texas, 78258, United States

Location

Webster

Webster, Texas, 77598, United States

Location

Norfolk

Norfolk, Virginia, 23507, United States

Location

Richmond

Richmond, Virginia, 23225, United States

Location

Spokane

Spokane, Washington, 99207, United States

Location

Porto Alegre

Porto Alegre, Rio Grande do Sul, 90510-040, Brazil

Location

São Bernardo do Campo

São Bernardo do Campo, São Paulo, 09715-090, Brazil

Location

Sao Paulo

São Paulo, São Paulo, 01317-000, Brazil

Location

Porto Alegre

Porto Alegre, 90510-040, Brazil

Location

São Paulo

São Paulo, 04266-010, Brazil

Location

Providencia

Providencia, 7510186, Chile

Location

San Ramon

San Ramón, 8880465, Chile

Location

Santiago

Santiago, 8360160, Chile

Location

České Budějovice

České Budějovice, 370 01, Czechia

Location

Olomouc

Olomouc, 772 00, Czechia

Location

Pisek

Písek, 39701, Czechia

Location

Kecskemét

Kecskemét, Bács-Kiskun county, 6000, Hungary

Location

Debrecen

Debrecen, 4024, Hungary

Location

Debrecen

Debrecen, 4025, Hungary

Location

Gyula

Gyula, 5700, Hungary

Location

Nyíregyháza

Nyíregyháza, 4400, Hungary

Location

Szentes

Szentes, 6600, Hungary

Location

Catanzaro

Catanzaro, 88100, Italy

Location

Roma

Roma, 00168, Italy

Location

SIENA

Siena, 53100, Italy

Location

Torino

Torino, 10126, Italy

Location

Szczecin

Szczecin, West Pomeranian Voivodeship, 71-270, Poland

Location

Bialystok

Bialystok, 15-464, Poland

Location

Katowice

Katowice, 40-123, Poland

Location

Poznan

Poznan, 60-192, Poland

Location

Warszawa

Warsaw, 02-201, Poland

Location

Bloemfontein

Bloemfontein, Free State, 9301, South Africa

Location

Centurion

Centurion, Gauteng, 0157, South Africa

Location

Cape Town

Cape Town, Western Cape, 7405, South Africa

Location

Cape Town

Cape Town, Western Cape, 7500, South Africa

Location

Durban

Durban, 4126, South Africa

Location

Roodepoort

Roodepoort, 1724, South Africa

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

MyofibromaLeiomyomaMenorrhagia

Interventions

relugolixestradiol, norethindrone drug combination

Condition Hierarchy (Ancestors)

Neoplasms, Connective TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsConnective Tissue DiseasesSkin and Connective Tissue DiseasesNeoplasms, Muscle TissueUterine HemorrhageUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and SymptomsMenstruation Disturbances

Results Point of Contact

Title
Clinical Trials at Myovant
Organization
Myovant Sciences GmbH

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Randomized withdrawal following an open-label extension to a randomized controlled parent study
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 13, 2018

First Posted

November 23, 2018

Study Start

October 16, 2018

Primary Completion

February 19, 2021

Study Completion

October 20, 2021

Last Updated

June 25, 2024

Results First Posted

June 25, 2024

Record last verified: 2024-05

Data Sharing

IPD Sharing
Will not share

Locations