Clinical trial NCT03751124: Study of Relugolix With Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uterine Leiomyoma
Uterine Fibroids
Keywords: Heavy menstrual bleeding
Menorrhagia
Uterine Fibroids
Uterine Leiomyoma
Lead sponsor: Myovant Sciences GmbH
Sponsor class: INDUSTRY
First posted: 2018-11-23
Enrollment: 229
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 51
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized withdrawal following an open-label extension to a randomized controlled parent study
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage Of Participants Who Maintained MBL Volume Of <80 Milliliters (mL) At Week 76 During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 76
Secondary outcomes:
measure: Time To MBL Volume ≥80 mL During The Randomized Treatment Period
timeFrame: From Week 52/Baseline through Week 104
measure: Percentage Of Participants Who Maintained MBL Volume Of <80 mL At Week 104 During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 104
measure: Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 76 During The Randomized Treatment Period
timeFrame: Week 76
measure: Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Percentage Change From Week 52/Baseline To Week 76 In MBL Volume During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Percentage Change From Week 52/Baseline To Week 104 In MBL Volume During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Percentage Of Participants Achieving Or Maintaining Amenorrhea At Week 104 During The Randomized Treatment Period
timeFrame: Week 104
measure: Percentage Of Participants Who Responded (MBL Volume <80 mL) To Retreatment During The Retreatment Period
timeFrame: From Initiation of Retreatment to Week 104
measure: Percentage Of Participants Whose Menses Had Resumed During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76 and Week 104
measure: Time To Resumption Of Menses For Participants Who Were Amenorrhoeic At Week 52/Baseline During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 104
measure: Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Percentage Of Participants With MBL Volume Of ≥80 mL At Week 76 And Week 104 During the Randomized Treatment Period
timeFrame: From Week 52/Baseline to Week 76 and Week 104
measure: Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 64
measure: Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Percent Change From Week 52/Baseline In Hemoglobin Concentration During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Percentage Of Participants Who Had Hemoglobin Level ≤10.5 g/dL Over Time During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Percentage Of Participants Who Had Hemoglobin Level <11.6 g/dL Over Time During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Change From Week 52/Baseline In Short Form 36v2 (SF-36v2) Domain During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Change From Week 52/Baseline In SF-36v2 Summary Component Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Function During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Categorical Change From Week 52/Baseline In PGA For Uterine Fibroid-related Symptoms During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Work Time Missed Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 76
measure: Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Work Time Missed Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 104
measure: Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Impairment While Working Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 76
measure: Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Impairment While Working Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 104
measure: Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Overall Work Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 76
measure: Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Overall Work Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 104
measure: Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Activity Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 76
measure: Change From Week 52/Baseline In The Work Productivity Activity Impairment - Percent Activity Impairment Due to Uterine Fibroids (WPAI-UF) Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline up to Week 104
measure: Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Change From Week 52/Baseline In The UFS-QoL Bleeding And Pelvic Discomfort Score During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Original: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: New: Change From Week 52/Baseline In The UFS-QoL Symptom Severity Score During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 76
measure: Change From Week 52/Baseline In The UFS-QoL Score by Health-Related Quality Of Life Subscale And Total Scores During The Randomized Treatment Period
timeFrame: Week 52/Baseline to Week 104
measure: Predose Concentration Of Estradiol At Week 56
timeFrame: Week 52/Baseline and Week 56
measure: Participants With Adverse Events (AEs) As A Measure Of Safety And Tolerability
timeFrame: Week 52/Baseline up to Week 104
measure: Percent Change From Week 52/Baseline In BMD At Lumbar Spine (L1-L4)
timeFrame: Week 52/Baseline to Week 104
measure: Percent Change From Week 52/Baseline In BMD At Femoral Neck And Total Hip
timeFrame: Week 52/Baseline to Week 104
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham
state: Alabama
city: Mesa
country: United States
facility: Mesa
state: Arizona
city: Tucson
country: United States
facility: Tucson
state: Arizona
city: Canoga Park
country: United States
facility: Canoga Park
state: California
city: Huntington Beach
country: United States
facility: Huntington Beach
state: California
city: La Mesa
country: United States
facility: La Mesa
state: California
city: Los Angeles
country: United States
facility: Los Angeles
state: California
city: Norwalk
country: United States
facility: Norwalk
state: California
city: San Diego
country: United States
facility: San Diego
state: California
city: Denver
country: United States
facility: Denver
state: Colorado
city: Lakewood
country: United States
facility: Lakewood
state: Colorado
city: Aventura
country: United States
facility: Aventura
state: Florida
city: Clearwater
country: United States
facility: Clearwater
state: Florida
city: DeLand
country: United States
facility: Deland
state: Florida
city: Fort Lauderdale
country: United States
facility: Ft. Lauderdale
state: Florida
city: Fort Myers
country: United States
facility: Fort Myers
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville
state: Florida
city: Jupiter
country: United States
facility: Jupiter
state: Florida
city: Margate
country: United States
facility: Margate
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: Orlando
country: United States
facility: Orlando
state: Florida
city: Oviedo
country: United States
facility: Oviedo
state: Florida
city: Sarasota
country: United States
facility: Sarasota
state: Florida
city: Tampa
country: United States
facility: Tampa
state: Florida
city: West Palm Beach
country: United States
facility: United States, Florida
state: Florida
city: West Palm Beach
country: United States
facility: West Palm Beach
state: Florida
city: Weston
country: United States
facility: Weston
state: Florida
city: Atlanta
country: United States
facility: Atlanta
state: Georgia
city: Augusta
country: United States
facility: Augusta
state: Georgia
city: College Park
country: United States
facility: College Park
state: Georgia
city: Decatur
country: United States
facility: Dacatur
state: Georgia
city: Duluth
country: United States
facility: Duluth
state: Georgia
city: Norcross
country: United States
facility: Norcross
state: Georgia
city: Savannah
country: United States
facility: Savannah
state: Georgia
city: Smyrna
country: United States
facility: Smyrna
state: Georgia
city: Chicago
country: United States
facility: Chicago
state: Illinois
city: Oak Brook
country: United States
facility: Oak brook
state: Illinois
city: Shawnee Mission
country: United States
facility: Shawnee
state: Kansas
city: Covington
country: United States
facility: Covington
state: Louisiana
city: Marrero
country: United States
facility: Marrero
state: Louisiana
city: Metairie
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facility: Metairie
state: Louisiana
city: Baltimore
country: United States
facility: Baltimore
state: Maryland
city: Towson
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facility: Towson
state: Maryland
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facility: Canton
state: Michigan
city: Detroit
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facility: Detroit
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city: Las Vegas
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facility: Las Vegas
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas
state: Nevada
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state: New Jersey
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facility: Williamsville
state: New York
city: Durham
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state: North Carolina
city: Raleigh
country: United States
facility: Raleigh
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh
state: North Carolina
city: Winston-Salem
country: United States
facility: Winston Salem
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati
state: Ohio
city: Bluffton
country: United States
facility: Bluffton
state: South Carolina
city: Charleston
country: United States
facility: Charleston
state: South Carolina
city: Columbia
country: United States
facility: Columbia
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga
state: Tennessee
city: Memphis
country: United States
facility: Memphis
state: Tennessee
city: Memphis
country: United States
facility: Memphis
state: Tennessee
city: Dallas
country: United States
facility: Dallas
state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: Longview
country: United States
facility: Longview
state: Texas
city: San Antonio
country: United States
facility: San Antonio
state: Texas
city: San Antonio
country: United States
facility: San Antonio
state: Texas
city: Webster
country: United States
facility: Webster
state: Texas
city: Norfolk
country: United States
facility: Norfolk
state: Virginia
city: Richmond
country: United States
facility: Richmond
state: Virginia
city: Spokane
country: United States
facility: Spokane
state: Washington
city: Porto Alegre
country: Brazil
facility: Porto Alegre
state: RIO Grande DO SUL
city: São Bernardo Do Campo
country: Brazil
facility: São Bernardo do Campo
state: SAO Paulo
city: São Paulo
country: Brazil
facility: Sao Paulo
state: Sao Paulo
city: Porto Alegre
country: Brazil
facility: Porto Alegre
city: São Paulo
country: Brazil
facility: São Paulo
city: Providencia
country: Chile
facility: Providencia
city: San Ramón
country: Chile
facility: San Ramon
city: Santiago
country: Chile
facility: Santiago
city: Olomouc
country: Czechia
facility: Olomouc
city: Písek
country: Czechia
facility: Pisek
city: České Budějovice
country: Czechia
facility: České Budějovice
city: Kecskemét
country: Hungary
facility: Kecskemét
state: Bacs-kiskun
city: Debrecen
country: Hungary
facility: Debrecen
city: Debrecen
country: Hungary
facility: Debrecen
city: Gyula
country: Hungary
facility: Gyula
city: Nyíregyháza
country: Hungary
facility: Nyíregyháza
city: Szentes
country: Hungary
facility: Szentes
city: Catanzaro
country: Italy
facility: Catanzaro
city: Roma
country: Italy
facility: Roma
city: Siena
country: Italy
facility: SIENA
city: Torino
country: Italy
facility: Torino
city: Szczecin
country: Poland
facility: Szczecin
state: Zachodniopomorskie
city: Białystok
country: Poland
facility: Bialystok
city: Katowice
country: Poland
facility: Katowice
city: Poznan
country: Poland
facility: Poznan
city: Warszawa
country: Poland
facility: Warszawa
city: Bloemfontein
country: South Africa
facility: Bloemfontein
state: Free State
city: Centurion
country: South Africa
facility: Centurion
state: Gauteng
city: Cape Town
country: South Africa
facility: Cape Town
state: Western Cape
city: Cape Town
country: South Africa
facility: Cape Town
state: Western Cape
city: Durban
country: South Africa
facility: Durban
city: Roodepoort
country: South Africa
facility: Roodepoort
Study officials:
References: