LIBERTY 2: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

NCT03103087 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: MVT-601-30022016-005113-50
• Study Type: interventional
• Target: 382
• Locations: 8 countries
• Sites: 127

Brief Summary

The purpose of this study is to determine the benefit of relugolix 40 milligrams (mg) once a day co-administered with estradiol (E2) 1 mg and norethindrone acetate (NETA) 0.5 mg compared with placebo for 24 weeks on heavy menstrual bleeding associated with uterine fibroids.

Conditions

Heavy Menstrual Bleeding; Uterine Fibroid

Keywords

Uterine Fibroid; Heavy Menstrual Bleeding; Menstrual Blood Volume

Outcome Measures

Primary Outcomes (1)

• Percentage Of Participants Who Achieved A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume With Relugolix Plus E2/NETA

  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 24). 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 24/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. As per the objective of the study, the pre-specified primary efficacy analyses compared relugolix plus E2/NETA with placebo. Therefore, only relugolix plus E2/NETA and placebo arms are presented.

  From Baseline up to the last 35 days of treatment (up to Week 24)

Secondary Outcomes (43)

• Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment

  From Baseline up to last 35 days of treatment (up to Week 24)

• Percent Change From Baseline At Week 24 In MBL Volume

  Baseline, Week 24

• Percentage Of Participants With A Hemoglobin Level ≤ 10.5 g/dL At Baseline Who Achieved An Increase Of > 2 g/dL From Baseline At Week 24

  From Baseline up to Week 24

• Percentage Of Participants With A Maximum Numerical Rating Scale (NRS) Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment

  From Baseline up to Week 24

• Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume

  Baseline Week 24

Study Arms (3)

Relugolix plus E2/NETA (Group A)

EXPERIMENTAL

Relugolix co-administered with E2/NETA for 24 weeks.

Drug: Relugolix; Drug: Estradiol/norethindrone acetate

Relugolix plus Delayed E2/NETA (Group B)

EXPERIMENTAL

Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.

Drug: Relugolix; Drug: Estradiol/norethindrone acetate; Drug: Estradiol/norethindrone acetate placebo

Placebo (Group C)

PLACEBO COMPARATOR

Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.

Drug: Relugolix placebo; Drug: Estradiol/norethindrone acetate placebo

Interventions

Relugolix DRUG

Relugolix (40 mg) tablet administered orally once daily.

Also known as: TAK-385, MVT-601

Relugolix plus Delayed E2/NETA (Group B); Relugolix plus E2/NETA (Group A)

Estradiol/norethindrone acetate DRUG

E2 (1.0 mg)/NETA (0.5 mg) co-formulated capsule administered orally once daily.

Also known as: E2/NETA, low-dose hormonal add-back

Relugolix plus Delayed E2/NETA (Group B); Relugolix plus E2/NETA (Group A)

Relugolix placebo DRUG

Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.

Placebo (Group C)

Estradiol/norethindrone acetate placebo DRUG

E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the capsule containing E2/NETA in size, shape, color, and odor.

Also known as: E2/NETA placebo

Placebo (Group C); Relugolix plus Delayed E2/NETA (Group B)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal female aged 18 to 50 years old (inclusive) on the day of signing and dating the informed consent form.
• Has regularly occurring menstrual periods of ≤ 14 days duration with a cycle of 21 to 38 days from the start of 1 menstrual period until the start of the next, by participant history for at least 3 months prior to the first screening visit.
• Has a diagnosis of uterine fibroids that is confirmed by a transvaginal and/or transabdominal ultrasound performed during the screening period.
• Has heavy menstrual bleeding associated with uterine fibroids as evidenced by an MBL of ≥ 160 milliliter (mL) during 1 cycle or ≥ 80 mL per cycle for 2 menstrual cycles as measured by the alkaline hematin method during the screening period.

You may not qualify if:

• Has transvaginal and/or transabdominal ultrasound during the screening period demonstrating pathology other than uterine fibroids that could be responsible for or contributing to the participant's heavy menstrual bleeding.
• Has known rapidly enlarging uterine fibroids in the opinion of the investigator.
• Has a weight that exceeds the weight limit of the DXA scanner or has a condition that precludes an adequate DXA measurement at the lumbar spine and proximal femur.
• Has a history of or currently has osteoporosis, or other metabolic bone disease, hyperparathyroidism, hyperprolactinemia, hyperthyroidism, anorexia nervosa, or low traumatic (from the standing position) or atraumatic fracture (toe, finger, skull, face and ankle fractures are allowed). A history of successfully treated hyperparathyroidism, hyperprolactinemia, or hyperthyroidism is allowed if the participant's bone mineral density is within normal limits.
• Has a history of the use of bisphosphonates, calcitonin, calcitriol, ipriflavone, teriparatide, denosumab, or any medication other than calcium and vitamin D preparations to treat bone mineral density loss.
• Has been a participant in an investigational drug or device study within the 1 month prior to the first screening visit.

Sponsors & Collaborators

• Myovant Sciences GmbH: lead

Study Sites (127)

Birmingham

Birmingham, Alabama, 35205, United States

Location

Mesa

Mesa, Arizona, 85209, United States

Location

Tucson

Tucson, Arizona, 85704, United States

Location

Tuscon

Tucson, Arizona, 85712, United States

Location

Canoga Park

Canoga Park, California, 91303, United States

Location

Huntington Beach

Huntington Beach, California, 92647, United States

Location

Long Beach

Long Beach, California, 90806, United States

Location

Los Angeles

Los Angeles, California, 90036, United States

Location

Los Angeles

Los Angeles, California, 90057, United States

Location

Panorama

Panorama City, California, 91402, United States

Location

San Diego

San Diego, California, 92114, United States

Location

Upland

Upland, California, 91786, United States

Location

Denver

Denver, Colorado, 80209, United States

Location

Lakewood

Lakewood, Colorado, 80228, United States

Location

Washington

Washington D.C., District of Columbia, 20036, United States

Location

Aventura

Aventura, Florida, 33180, United States

Location

DeLand

DeLand, Florida, 32720, United States

Location

Ft. Lauderdale

Fort Lauderdale, Florida, 33316, United States

Location

Jupiter

Jupiter, Florida, 33458, United States

Location

Lake City

Lake City, Florida, 32055, United States

Location

Loxahachee

Loxahatchee Groves, Florida, 33470, United States

Location

Miami

Miami, Florida, 33126, United States

Location

Miami

Miami, Florida, 33155, United States

Location

Miami Springs

Miami Springs, Florida, 33166, United States

Location

New Port Richey

New Port Richey, Florida, 34652, United States

Location

North Miami

North Miami, Florida, 33161, United States

Location

Oviedo

Oviedo, Florida, 32765, United States

Location

Plantation

Plantation, Florida, 33324, United States

Location

Port St. Lucie

Port Saint Lucie, Florida, 34952, United States

Location

Saint Cloud

Saint Cloud, Florida, 34769, United States

Location

Sarasota

Sarasota, Florida, 34239, United States

Location

Stuart

Stuart, Florida, 34996, United States

Location

Tampa

Tampa, Florida, 33606, United States

Location

Wellington

Wellington, Florida, 33414, United States

Location

West Palm Beach

West Palm Beach, Florida, 33409, United States

Location

Atlanta

Atlanta, Georgia, 30312, United States

Location

Decatur

Decatur, Georgia, 30034, United States

Location

Duluth

Duluth, Georgia, 30097, United States

Location

Norcross

Norcross, Georgia, 30093, United States

Location

Sandy Springs

Sandy Springs, Georgia, 30328, United States

Location

Savannah

Savannah, Georgia, 31406, United States

Location

Idaho Falls

Idaho Falls, Idaho, 83404, United States

Location

Nampa

Nampa, Idaho, 83686, United States

Location

Champaign

Champaign, Illinois, 61820, United States

Location

Chicago

Chicago, Illinois, 60611, United States

Location

Naperville

Naperville, Illinois, 60540, United States

Location

Oakbrook

Oak Brook, Illinois, 60523, United States

Location

Avon

Avon, Indiana, 46123, United States

Location

Shawnee

Shawnee Mission, Kansas, 66128, United States

Location

Marrero

Marrero, Louisiana, 70072, United States

Location

Metairie

Metairie, Louisiana, 70006, United States

Location

New Orleans

New Orleans, Louisiana, 70115, United States

Location

Baltimore

Baltimore, Maryland, 21208, United States

Location

Towson

Towson, Maryland, 21204, United States

Location

Bay City

Bay City, Michigan, 48706, United States

Location

Canton

Canton, Michigan, 48187, United States

Location

Detroit

Detroit, Michigan, 48201, United States

Location

Saginaw

Saginaw, Michigan, 48604, United States

Location

Norfolk

Norfolk, Nebraska, 68701, United States

Location

Las Vegas

Las Vegas, Nevada, 89106, United States

Location

Las Vegas

Las Vegas, Nevada, 89109, United States

Location

Las Vegas

Las Vegas, Nevada, 89113, United States

Location

New Brunswick

New Brunswick, New Jersey, 08901, United States

Location

Albuquerque

Albuquerque, New Mexico, 87102, United States

Location

Brooklyn

Brooklyn, New York, 11201, United States

Location

New York

New York, New York, 10022, United States

Location

New York

New York, New York, 10038, United States

Location

Rochester

Rochester, New York, 14642, United States

Location

Durham

Durham, North Carolina, 27713, United States

Location

Raleigh

Raleigh, North Carolina, 27607, United States

Location

Winston Salem

Winston-Salem, North Carolina, 27103, United States

Location

Cincinnati

Cincinnati, Ohio, 45212, United States

Location

Columbus

Columbus, Ohio, 43231, United States

Location

West Reading

West Reading, Pennsylvania, 19611, United States

Location

Charleston

Charleston, South Carolina, 29406, United States

Location

Beaumont

Beaumont, Texas, 77702, United States

Location

Dallas

Dallas, Texas, 75231, United States

Location

Dallas

Dallas, Texas, 75234, United States

Location

Fort Worth

Fort Worth, Texas, 76104, United States

Location

Frisco

Frisco, Texas, 75035, 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, 78258, United States

Location

Virginia Beach

Norfolk, Virginia, 23502, United States

Location

Richmond

Richmond, Virginia, 23225, United States

Location

Covington

Covington, Washington, 98042, United States

Location

Puyallup

Puyallup, Washington, 98372, United States

Location

Spokane

Spokane, Washington, 99207, United States

Location

Brussels

Brussels, 1070, Belgium

Location

Brussels

Brussels, 1200, Belgium

Location

Ghent

Ghent, 9000, Belgium

Location

Jette

Jette, 1090, Belgium

Location

La Louvière

La Louvière, 7100, Belgium

Location

Botucatu

Botucatu, 18618-686, Brazil

Location

Porto Alegre

Porto Alegre, 90035-903, Brazil

Location

Porto Alegre

Porto Alegre, 90510-040, Brazil

Location

São Paulo

São Paulo, 04266-010, Brazil

Location

Santiago

Santiago, Providencia, 7510186, Chile

Location

San Ramon

San Ramón, 8880465, Chile

Location

Santiago

Santiago, 8320165, Chile

Location

Santiago

Santiago, 8360160, Chile

Location

Ceské Budejovice

České Budějovice, 370 01, Czechia

Location

Jihlava

Jihlava, 586 33, Czechia

Location

Nachod

Náchod, 54701, Czechia

Location

Olomouc

Olomouc, 772 00, Czechia

Location

Ostrava

Ostrava, 708 52, Czechia

Location

Pisek

Písek, 39701, Czechia

Location

Debrecen

Debrecen, Hajdu, 4032, Hungary

Location

Nyíregyháza

Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary

Location

Budapest

Budapest, 1106, Hungary

Location

Debrecen

Debrecen, 4025, Hungary

Location

Gyula

Gyula, 5700, Hungary

Location

Kecskemét

Kecskemét, 6000, Hungary

Location

Pecs

Pécs, 7624, Hungary

Location

Szentes

Szentes, 6600, Hungary

Location

Poznan

Poznan, Greater Poland Voivodeship, 60-192, Poland

Location

Krakow

Krakow, Lesser Poland Voivodeship, 30114, Poland

Location

Rzeszów

Rzeszów, Masovian Voivodeship, 35302, Poland

Location

Białystok

Bialystok, Podlaskie Voivodeship, 15224, Poland

Location

Bialystok

Bialystok, Podlaskie Voivodeship, 15464, Poland

Location

Katowice

Katowice, Silesian Voivodeship, 40724, Poland

Location

Gdańsk

Gdansk, 80850, Poland

Location

Cape Town

Cape Town, Western Cape, 7405, South Africa

Location

Bloemfontein

Bloemfontein, 9301, South Africa

Location

Centurion

Centurion, 00157, South Africa

Location

Parow

Parow, 7500, South Africa

Location

Related Publications (9)

• Catherino WH, Al-Hendy A, Zaim S, Bouzegaou N, Venturella R, Stewart EA, Wu R, Vannuccini S, Perry JS, Rakov VG, Munro MG. Efficacy and safety of relugolix combination therapy in women with uterine fibroids and adenomyosis: subgroup analysis of LIBERTY 1 and LIBERTY 2. Fertil Steril. 2025 Sep;124(3):523-533. doi: 10.1016/j.fertnstert.2025.04.037. Epub 2025 May 2.

  PMID: 40320117 DERIVED

• Stewart EA, Lukes AS, Venturella R, Ferreira JA, Li Y, Hunsche E, Wagman RB, Al-Hendy A. A plain language summary describing changes in pain associated with uterine fibroids among women receiving relugolix combination therapy. Pain Manag. 2024 Sep;14(9):469-476. doi: 10.1080/17581869.2024.2408114. Epub 2024 Oct 28.

  PMID: 39466126 DERIVED

• Stewart EA, Al-Hendy A, Lukes AS, Madueke-Laveaux OS, Zhu E, Proehl S, Schulmann T, Marsh EE. Relugolix combination therapy in Black/African American women with symptomatic uterine fibroids: LIBERTY Long-Term Extension study. Am J Obstet Gynecol. 2024 Feb;230(2):237.e1-237.e11. doi: 10.1016/j.ajog.2023.10.030. Epub 2023 Oct 18.

  PMID: 37863160 DERIVED

• Al-Hendy A, Lukes AS, Venturella R, Villarroel C, McKain L, Li Y, Wagman RB, Stewart EA. A plain language summary of the long-term relugolix combination therapy study for uterine fibroids. J Comp Eff Res. 2023 Aug;12(8):e230069. doi: 10.57264/cer-2023-0069. Epub 2023 Jul 21.

  PMID: 37477173 DERIVED

• Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, Critchley HO, Li Y, McKain L, Arjona Ferreira JC, Langenberg AG, Wagman RB, Stewart EA. A plain language summary of the safety of relugolix combination therapy and improvement in symptoms in women with uterine fibroids from the LIBERTY 1 and LIBERTY 2 studies. Pain Manag. 2023 Apr;13(4):205-211. doi: 10.2217/pmt-2022-0085. Epub 2023 May 15.

  PMID: 37183454 DERIVED

• 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.

  PMID: 36357960 DERIVED

• Stewart EA, Lukes AS, Venturella R, Arjona Ferreira JC, Li Y, Hunsche E, Wagman RB, Al-Hendy A. Relugolix Combination Therapy for Uterine Leiomyoma-Associated Pain in the LIBERTY Randomized Trials. Obstet Gynecol. 2022 Jun 1;139(6):1070-1081. doi: 10.1097/AOG.0000000000004787. Epub 2022 May 2.

  PMID: 35675604 DERIVED

• Hunsche E, Rakov V, Scippa K, Witherspoon B, McKain L. The Burden of Uterine Fibroids from the Perspective of US Women Participating in Open-Ended Interviews. Womens Health Rep (New Rochelle). 2022 Mar 4;3(1):286-296. doi: 10.1089/whr.2021.0086. eCollection 2022.

  PMID: 35415708 DERIVED

• Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, Critchley HOD, Li Y, McKain L, Arjona Ferreira JC, Langenberg AGM, Wagman RB, Stewart EA. Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. N Engl J Med. 2021 Feb 18;384(7):630-642. doi: 10.1056/NEJMoa2008283.

  PMID: 33596357 DERIVED

MeSH Terms

Conditions

Menorrhagia; Leiomyoma

Interventions

relugolix; estradiol, norethindrone drug combination; Estradiol

Condition Hierarchy (Ancestors)

Uterine Hemorrhage; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

None reported

Results Point of Contact

• Title: Clinical Trials at Myovant
• Organization: Myovant Sciences GmbH

clinicaltrials@myovant.com

+1 650 238 0250

Study Officials

• Myovant Medical Monitor

  Myovant Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: April 6, 2017
• Study Start: June 14, 2017
• Primary Completion: July 10, 2019
• Study Completion: September 16, 2020
• Last Updated: April 20, 2022
• Results First Posted: April 20, 2022

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (89); BE (5); HU (8); PL (7); ZA (4); CZ (6); CL (4); BR (4)