Clinical trial NCT03103087: LIBERTY 2: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Official title: LIBERTY 2: An International Phase 3 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate Relugolix Co-Administered With and Without Low-Dose Estradiol and Norethindrone Acetate in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heavy Menstrual Bleeding
Uterine Fibroid
Keywords: Uterine Fibroid
Heavy Menstrual Bleeding
Menstrual Blood Volume
Lead sponsor: Myovant Sciences GmbH
Sponsor class: INDUSTRY
First posted: 2017-04-06
Enrollment: 382
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This study is an international phase 3 randomized, double-blind, placebo-controlled efficacy and safety study to evaluate 24 weeks of oral daily relugolix 40 mg co-administered with low-dose E2 and NETA (Group A) and 12 weeks of daily oral relugolix 40 mg alone followed by 12 weeks of daily oral relugolix 40 mg co-administered with low-dose E2 and NETA (Group B) compared with 24 weeks of placebo (Group C).

All participants completing the Week 24 visit, including participants randomized to placebo, were offered the opportunity to enroll in an open-label extension study in which all eligible participants will receive relugolix co-administered with low-dose E2 and NETA. Participants who did not enroll into the extension study had a follow-up visit approximately 30 days after the end of treatment (that is, after the participant's last dose of study medication).

Safety will be assessed throughout the study by monitoring adverse events, vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and assessments of bone mineral density.

Eligibility criteria: Key Inclusion Criteria:

1. Premenopausal female aged 18 to 50 years old (inclusive) on the day of signing and dating the informed consent form.
2. 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.
3. Has a diagnosis of uterine fibroids that is confirmed by a transvaginal and/or transabdominal ultrasound performed during the screening period.
4. 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.

Key Exclusion Criteria:

1. 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.
2. Has known rapidly enlarging uterine fibroids in the opinion of the investigator.
3. 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.
4. 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.
5. 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.
6. Has been a participant in an investigational drug or device study within the 1 month prior to the first screening visit.

Primary outcomes:
measure: 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
timeFrame: From Baseline up to the last 35 days of treatment (up to Week 24)
Secondary outcomes:
measure: Percentage Of Participants With Amenorrhea Over The Last 35 Days Of Treatment
timeFrame: From Baseline up to last 35 days of treatment (up to Week 24)
measure: Percent Change From Baseline At Week 24 In MBL Volume
timeFrame: Baseline, Week 24
measure: 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
timeFrame: From Baseline up to Week 24
measure: Percentage Of Participants With A Maximum Numerical Rating Scale (NRS) Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment
timeFrame: From Baseline up to Week 24
measure: Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume
timeFrame: Baseline Week 24
measure: Percent Change From Baseline At Week 24 In Uterine Volume
timeFrame: From Baseline up to Week 24
measure: Change From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL (Q1, Q2, Q5)
timeFrame: Baseline Week 24
measure: Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 to L4) As Assessed By DXA
timeFrame: From Baseline up to Week 12
measure: Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 To L4), Total Hip, And Femoral Neck As Assessed By DXA
timeFrame: Baseline through Week 24
measure: Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12
timeFrame: Baseline through Week 12
measure: Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24
timeFrame: Baseline through Week 24
measure: Predose Trough Concentrations Of Relugolix And NET In The Relugolix Plus E2/NETA Group At Week 24
timeFrame: Week 24
measure: Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24
timeFrame: Week 24
measure: Change From Baseline At Week 24 In Predose Concentrations Of E2 In The Relugolix Plus E2/NETA Group
timeFrame: Baseline, Week 24
measure: Time To MBL Response
timeFrame: From Baseline through Week 24
measure: Sustained Amenorrhea Rate (No Or Negligible Bleeding)
timeFrame: Week 24
measure: Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding)
timeFrame: From Baseline through Week 24
measure: Time To Achieving Amenorrhea (No Or Negligible Bleeding)
timeFrame: From Baseline through Week 24
measure: Number Of Participants With Hemoglobin ≤ 10.5 g/dL At Baseline And Achieved An Increase Of > 2 g/dL At Week 24
timeFrame: From Baseline through Week 24
measure: Percent Change From Baseline At Week 24 In Hemoglobin For Women With A Hemoglobin Concentration ≤ 10.5 g/dL At Baseline
timeFrame: Baseline, Week 24
measure: Number Of Participants With Hemoglobin Increase Of ≥ 1 g/dL From Baseline To Week 24 Among Those With Below Lower Limit Of Normal
timeFrame: Week 24
measure: Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score
timeFrame: Baseline, Week 24
measure: Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score
timeFrame: Baseline, Week 24
measure: Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score
timeFrame: Baseline, Week 24
measure: Change From Baseline In UFS-QoL Score by Health-Related Quality of Life Total Score
timeFrame: Baseline, Week 24
measure: Number Of Responders With At Least 20 Points Increase From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score
timeFrame: From Baseline through Week 24
measure: Change From Baseline in UFS-QoL Bleeding and Pelvic Discomfort Scale Score
timeFrame: Baseline, Week 24
measure: Number Of Responders With At Least 20 Points Decrease in UFS-QoL Bleeding And Pelvic Discomfort Scale Score
timeFrame: Baseline, Week 24
measure: Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11
timeFrame: Baseline, Week 24
measure: Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20
timeFrame: Baseline, Week 24
measure: Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29
timeFrame: Baseline, Week 24
measure: Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire
timeFrame: Baseline, Week 24
measure: Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire
timeFrame: Baseline, Week 24
measure: Participants Achieving Improvement From Baseline In PGA Questionnaire For Symptoms From Baseline At Week 24
timeFrame: From Baseline through Week 24
measure: Participants Achieving Improvement From Baseline In PGA For Uterine Fibroid-related Function From Baseline At Week 24
timeFrame: From Baseline through Week 24
measure: Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities
timeFrame: Baseline, Week 24
measure: Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social Activities
timeFrame: Baseline, Week 24
measure: Number Of Participants Who Achieved A Maximum NRS Score ≤ 1 For Uterine Fibroid-associated Pain Over The Last 35 Days Of Treatment Who Had Maximum Pain Scores ≥ 4 During The 35 Days Prior To Randomization
timeFrame: From Baseline up to the last 35 days of treatment (up to 24 weeks)
measure: Number Of Participants With A ≥ 30% Reduction in NRS Score From Baseline to Last 35 Days of Treatment Who Had Maximum Pain Scores ≥ 4 At Baseline
timeFrame: Baseline, Week 24
measure: Change From Baseline In Luteinizing Serum Concentration At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In Follicle Stimulating Serum Concentration At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In E2 Serum Concentration At Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline In Progesterone Serum Concentration At Week 24
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
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country: United States
facility: Birmingham
state: Alabama
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facility: Mesa
state: Arizona
city: Tucson
country: United States
facility: Tucson
state: Arizona
city: Tucson
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facility: Tuscon
state: Arizona
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facility: Canoga Park
state: California
city: Huntington Beach
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facility: Huntington Beach
state: California
city: Long Beach
country: United States
facility: Long Beach
state: California
city: Los Angeles
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facility: Los Angeles
state: California
city: Los Angeles
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facility: Los Angeles
state: California
city: Panorama City
country: United States
facility: Panorama
state: California
city: San Diego
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facility: San Diego
state: California
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facility: Upland
state: California
city: Denver
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facility: Denver
state: Colorado
city: Lakewood
country: United States
facility: Lakewood
state: Colorado
city: Washington
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facility: Washington
state: District of Columbia
city: Aventura
country: United States
facility: Aventura
state: Florida
city: DeLand
country: United States
facility: DeLand
state: Florida
city: Fort Lauderdale
country: United States
facility: Ft. Lauderdale
state: Florida
city: Jupiter
country: United States
facility: Jupiter
state: Florida
city: Lake City
country: United States
facility: Lake City
state: Florida
city: Loxahatchee Groves
country: United States
facility: Loxahachee
state: Florida
city: Miami Springs
country: United States
facility: Miami Springs
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: Miami
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facility: Miami
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city: New Port Richey
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facility: New Port Richey
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city: North Miami
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facility: North Miami
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city: Oviedo
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facility: Oviedo
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city: Plantation
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facility: Plantation
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city: Port Saint Lucie
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facility: Port St. Lucie
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city: Saint Cloud
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facility: Saint Cloud
state: Florida
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facility: Sarasota
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city: Stuart
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city: Tampa
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city: Wellington
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city: West Palm Beach
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city: Atlanta
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facility: Atlanta
state: Georgia
city: Decatur
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facility: Decatur
state: Georgia
city: Duluth
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facility: Duluth
state: Georgia
city: Norcross
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facility: Norcross
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city: Sandy Springs
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facility: Sandy Springs
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city: Savannah
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city: Idaho Falls
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city: New Orleans
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city: Towson
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city: Bay City
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state: Michigan
city: Canton
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city: Detroit
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city: Saginaw
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city: Norfolk
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city: Las Vegas
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state: North Carolina
city: Raleigh
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facility: Raleigh
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city: Winston-Salem
country: United States
facility: Winston Salem
state: North Carolina
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facility: Cincinnati
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city: Dallas
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state: Texas
city: Dallas
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state: Texas
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state: Texas
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state: Texas
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state: Texas
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facility: Longview
state: Texas
city: San Antonio
country: United States
facility: San Antonio
state: Texas
city: Norfolk
country: United States
facility: Virginia Beach
state: Virginia
city: Richmond
country: United States
facility: Richmond
state: Virginia
city: Covington
country: United States
facility: Covington
state: Washington
city: Puyallup
country: United States
facility: Puyallup
state: Washington
city: Spokane
country: United States
facility: Spokane
state: Washington
city: Brussels
country: Belgium
facility: Brussels
city: Brussels
country: Belgium
facility: Brussels
city: Ghent
country: Belgium
facility: Ghent
city: Jette
country: Belgium
facility: Jette
city: La Louvière
country: Belgium
facility: La Louvière
city: Botucatu
country: Brazil
facility: Botucatu
city: Porto Alegre
country: Brazil
facility: Porto Alegre
city: Porto Alegre
country: Brazil
facility: Porto Alegre
city: São Paulo
country: Brazil
facility: São Paulo
city: Santiago
country: Chile
facility: Santiago
state: Providencia
city: San Ramón
country: Chile
facility: San Ramon
city: Santiago
country: Chile
facility: Santiago
city: Santiago
country: Chile
facility: Santiago
city: Jihlava
country: Czechia
facility: Jihlava
city: Náchod
country: Czechia
facility: Nachod
city: Olomouc
country: Czechia
facility: Olomouc
city: Ostrava
country: Czechia
facility: Ostrava
city: Písek
country: Czechia
facility: Pisek
city: České Budějovice
country: Czechia
facility: Ceské Budejovice
city: Debrecen
country: Hungary
facility: Debrecen
state: Hajdu
city: Nyíregyháza
country: Hungary
facility: Nyíregyháza
state: Szabolcs-Szatmar-Bereg
city: Budapest
country: Hungary
facility: Budapest
city: Debrecen
country: Hungary
facility: Debrecen
city: Gyula
country: Hungary
facility: Gyula
city: Kecskemét
country: Hungary
facility: Kecskemét
city: Pécs
country: Hungary
facility: Pecs
city: Szentes
country: Hungary
facility: Szentes
city: Krakow
country: Poland
facility: Krakow
state: Malopolskie
city: Rzeszów
country: Poland
facility: Rzeszów
state: Mazowieckie
city: Białystok
country: Poland
facility: Białystok
state: Podlaskie
city: Białystok
country: Poland
facility: Bialystok
state: Podlaskie
city: Katowice
country: Poland
facility: Katowice
state: Slaskie
city: Poznań
country: Poland
facility: Poznan
state: Wielkopolskie
city: Gdańsk
country: Poland
facility: Gdańsk
city: Cape Town
country: South Africa
facility: Cape Town
state: Western Cape
city: Bloemfontein
country: South Africa
facility: Bloemfontein
city: Centurion
country: South Africa
facility: Centurion
city: Parow
country: South Africa
facility: Parow
Study officials:
affiliation: Myovant Sciences
name: Myovant Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.