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

Uterine Fibroids Clinical Trial

Official title:

An International Phase 3 Double-Blind, Placebo-Controlled, Randomized Withdrawal Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03751124
• Other study ID #: MVT-601-035
• Secondary ID: 2018-001368-43
• Status: Completed
• Phase: Phase 3
• Start date: October 16, 2018
• Est. completion date: November 18, 2021

Study information

• Verified date: April 2022
• Source: Myovant Sciences GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 229
• Est. completion date: November 18, 2021
• Est. primary completion date: February 19, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 51 Years

Eligibility

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 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 OLE study.

Related Conditions & MeSH terms

• Hemorrhage
• Leiomyoma
• Menorrhagia
• Uterine Fibroids
• Uterine Leiomyoma

Intervention

Drug:
• Relugolix
Relugolix 40 mg tablet administered orally once daily
• Estradiol/norethindrone acetate
Capsule containing co-formulated tablet of estradiol 1.0 mg and norethindrone acetate 0.5 mg administered orally once daily
• Placebo for relugolix
Placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor
• Placebo for E2/NETA
Placebo capsule administered orally once daily and designed to match the E2/NETA capsule in size, shape, color, and odor

Locations

Country	Name	City	State
Brazil	Porto Alegre	Porto Alegre
Brazil	Porto Alegre	Porto Alegre	RIO Grande DO SUL
Brazil	São Bernardo do Campo	São Bernardo Do Campo	SAO Paulo
Brazil	Sao Paulo	São Paulo	Sao Paulo
Brazil	São Paulo	São Paulo
Chile	Providencia	Providencia
Chile	San Ramon	San Ramón
Chile	Santiago	Santiago
Czechia	Ceské Budejovice	Ceské Budejovice
Czechia	Olomouc	Olomouc
Czechia	Pisek	Písek
Hungary	Debrecen	Debrecen
Hungary	Debrecen	Debrecen
Hungary	Gyula	Gyula
Hungary	Kecskemét	Kecskemét	Bacs-kiskun
Hungary	Nyíregyháza	Nyíregyháza
Hungary	Szentes	Szentes
Italy	Catanzaro	Catanzaro
Italy	Roma	Roma
Italy	SIENA	Siena
Italy	Torino	Torino
Poland	Bialystok	Bialystok
Poland	Katowice	Katowice
Poland	Poznan	Poznan
Poland	Szczecin	Szczecin	Zachodniopomorskie
Poland	Warszawa	Warszawa
South Africa	Bloemfontein	Bloemfontein	Free State
South Africa	Cape Town	Cape Town	Western Cape
South Africa	Cape Town	Cape Town	Western Cape
South Africa	Centurion	Centurion	Gauteng
South Africa	Durban	Durban
South Africa	Roodepoort	Roodepoort
United States	Atlanta	Atlanta	Georgia
United States	Augusta	Augusta	Georgia
United States	Aventura	Aventura	Florida
United States	Baltimore	Baltimore	Maryland
United States	Birmingham	Birmingham	Alabama
United States	Bluffton	Bluffton	South Carolina
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	Clearwater	Clearwater	Florida
United States	College Park	College Park	Georgia
United States	Columbia	Columbia	South Carolina
United States	Covington	Covington	Louisiana
United States	Dallas	Dallas	Texas
United States	Dacatur	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	Ft. Lauderdale	Fort Lauderdale	Florida
United States	Fort Myers	Fort Myers	Florida
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	Lawrenceville	Lawrenceville	New Jersey
United States	Longview	Longview	Texas
United States	Los Angeles	Los Angeles	California
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	Miami	Miami	Florida
United States	Miami	Miami	Florida
United States	Miami	Miami	Florida
United States	Norcross	Norcross	Georgia
United States	Norfolk	Norfolk	Virginia
United States	Norwalk	Norwalk	California
United States	Oak brook	Oak Brook	Illinois
United States	Orlando	Orlando	Florida
United States	Oviedo	Oviedo	Florida
United States	Raleigh	Raleigh	North Carolina
United States	Raleigh	Raleigh	North Carolina
United States	Richmond	Richmond	Virginia
United States	San Antonio	San Antonio	Texas
United States	San Antonio	San Antonio	Texas
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	Smyrna	Smyrna	Georgia
United States	Spokane	Spokane	Washington
United States	Tampa	Tampa	Florida
United States	Towson	Towson	Maryland
United States	Tucson	Tucson	Arizona
United States	Webster	Webster	Texas
United States	United States, Florida	West Palm Beach	Florida
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,  Brazil,  Chile,  Czechia,  Hungary,  Italy,  Poland,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of women who maintain a menstrual blood loss (MBL) volume of < 80 mL	MBL volume is measured using the alkaline hematin method.	at Week 24 (Week 72 relative to the parent study baseline)
Secondary	Proportion of women who maintain a MBL volume of < 80 mL	MBL volume is measured using the alkaline hematin method.	at Week 52 (Week 104 relative to the parent study baseline)
Secondary	Change in MBL volume	MBL volume is measured using the alkaline hematin method.	from Baseline up to Week 52 (Week 104 relative to the parent study baseline)
Secondary	Proportion of women who responded (MBL volume < 80 mL) to retreatment during retreatment period	MBL volume is measured using the alkaline hematin method.	at Week 52 (Week 104 relative to the parent study baseline)
Secondary	Proportion of women with heavy menstrual bleeding	Defined as the proportion of women with MBL volume of = 80 mL at any time. MBL volume is measured using the alkaline hematin method.	at Week 24 and 52 (Week 72 and Week 104 relative to the parent study baseline)
Secondary	Time to resumption of heavy menstrual bleeding	Defined as time to MBL volume of = 80 mL. MBL volume is measured using the alkaline hematin method.	up to Week 52 (Week 104 relative to the parent study baseline)
Secondary	Proportion of women with suppression of bleeding	Will be assessed using patient daily diary and MBL volume measured using the alkaline hematin method.	at Week 24 and 52 (Week 72 and Week 104 relative to the parent study baseline)
Secondary	Time to resumption of menses in women who are amenorrhoeic	Will be assessed using patient daily diary.	up to Week 52 (Week 104 relative to the parent study baseline)
Secondary	Change in hemoglobin concentration	Blood samples will be collected from participants for hemoglobin measurements.	from Baseline up to Week 52 (Week 104 relative to the parent study baseline)
Secondary	Change in impact on quality of life: UFS-QOL	Assessed using the Uterine Fibroid Symptom Health-Related Quality of Life Questionnaire (UFS-QOL)	from Baseline up to Week 52 (Week 104 relative to the parent study baseline)
Secondary	Change in Patient Global Assessment (PGA) for symptoms	The PGA for symptoms is a 1-item questionnaire designed to assess participants impression of the severity of their symptoms related to uterine fibroids.	from Baseline up to Week 52 (Week 104 relative to the parent study baseline)
Secondary	Change in PGA for function	The PGA for function is a 1-item questionnaire designed to assess participants impression of how their symptoms related to uterine fibroids affected their usual activities.	from Baseline up to Week 52 (Week 104 relative to the parent study baseline)
Secondary	Bone Mineral Density (BMD)	Assessed by dual-energy X-ray absorptiometry (DXA) scan.	from parent study Baseline up to Week 104
Secondary	Percentage of participants with adverse events (AEs) as a measure of safety and tolerability	Assessed by percentage of participants with AEs and serious AEs.	up to 52 weeks
Secondary	Serum estradiol concentrations	Blood samples will be collected from participants for estradiol measurements.	up to 52 weeks