LIBERTY EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
- Conditions
- Heavy Menstrual BleedingUterine Fibroid
- Interventions
- Registration Number
- NCT03412890
- Lead Sponsor
- Myovant Sciences GmbH
- Brief Summary
The purpose of this study was to determine the long-term efficacy and safety of relugolix 40 milligrams (mg) once daily co-administered with estradiol (E2) and norethindrone acetate (NETA) for 28 weeks on heavy menstrual bleeding associated with uterine fibroids in participants who previously completed a 24-week treatment period in one of the pivotal studies (MVT-601-3001 or MVT-601-3002).
- Detailed Description
This study is an international phase 3 open-label, single-arm, long-term efficacy and safety extension study that enrolled eligible participants who have completed their participation in one of the phase 3 randomized, double-blind, placebo-controlled pivotal studies, MVT-601-3001 (LIBERTY 1 - NCT03049735) or MVT-601-3002 (LIBERTY 2 - NCT 03103087). All participants received relugolix 40 mg orally once daily co-administered with E2 (1 mg) and NETA (0.5 mg) for 28 weeks.
Approximately 600 women with heavy menstrual bleeding associated with uterine fibroids were to be enrolled, after having completed a 24-week treatment period in one of the pivotal studies. The objectives of the study were to evaluate long-term efficacy and safety through up to 52 weeks of treatment (including treatment during the pivotal study) of relugolix co-administered with E2/NETA.
Screening and baseline procedures were to be done at the same visit for this extension study (referred to as the "Week 24/Baseline Visit"), which coincided with the Week 24 Visit from the pivotal study and was to be defined as the date of completion of the last Week 24 procedure in the pivotal study. Participants will have received their last dose of study drug in the pivotal study on the day prior to the Week 24/Baseline Visit and were to receive their first dose of study drug for this extension study in the clinic after the participant was determined to be eligible for this extension study and provided informed consent to participate. The administration of the first dose of study drug for MVT-601-3003 was to define enrollment into this study. Study participants were to then take the open-label study treatment orally once daily for 28 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 477
- Completed 24 weeks of study drug treatment and study participation in either pivotal study, MVT-601-3001 or MVT-601-3002
Key
- 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 pivotal study (MVT-601-3001 or MVT-601-3002)
- Met a withdrawal criterion in the pivotal study (MVT-601-3001 or MVT-601-3002).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Relugolix plus E2/NETA Estradiol/norethindrone acetate Relugolix co-administered with E2/NETA for 28 weeks. Relugolix plus E2/NETA Relugolix Relugolix co-administered with E2/NETA for 28 weeks.
- Primary Outcome Measures
Name Time Method Percentage Of Participants Who Achieved Or Maintained An MBL Volume Of <80 Milliliters (mL) And At Least A 50% Reduction From Baseline MBL Volume At Week 52/End Of Treatment Week 52/End of Treatment 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 52). 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 52/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.
- Secondary Outcome Measures
Name Time Method Change From Pivotal Study Baseline In MBL Volume At Week 52 Week 52 MBL volume was measured using the alkaline hematin method, which involves chemically measuring the blood content of used feminine products. 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 least squares (LS) mean was derived for each treatment group using a mixed-effects model with repeated measure with visit, region, and Baseline MBL as fixed effects.
Change From Pivotal Study Baseline In Hemoglobin Concentration At Week 52 Week 52 Blood samples were collected from participants for hemoglobin measurements. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.
Change From Pivotal Study Baseline In The UFS-QoL Symptom Severity Scale At Week 52 Week 52 Transformed score ranges from 0 to 100 based on Likert scale (none of time, a little of time, some of the time, most of the time, and all of the time). Lower score indicates less distress and higher score indicates greater distress. A negative change from baseline indicates improvement. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.
Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At Week 52 Week 52 Assessed using the UFS-QoL questionnaire. The UFS-QoL subscale scores include items related to uterine fibroid-associated limitations/impairment in activities, revised activities, concern, energy/mood, control, self-consciousness, and sexual function. The scores were transformed to normalized scores. Transformed score ranges from 0 to 100. Higher scores are indicative of better health-related quality of life (high = good). The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.
Change From Pivotal Study Baseline In The UFS-QoL Score By Health-Related Quality of Life Total Score At Week 52 Week 52 Assessed using the UFS-QoL Questionnaire. The UFS-QoL total score was the sum of the subscales (concern, activities, revised activities, energy/mood, control, self-conscious, and sexual function). The raw scores were transformed to normalized scores. Transformed score ranges from 0 to 100. Higher scores are indicative of better health-related quality of life (high = good). The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.
Change From Pivotal Study Baseline In The Uterine Fibroid Symptom Health-Related Quality of Life (UFS-QoL) Bleeding And Pelvic Discomfort (BPD) Scale At Week 52 Week 52 The BPD scale has been derived from the UFS-QoL symptom severity scale. The scale consists of the following 3 symptoms proximal to uterine fibroids that are experienced by most participants: heavy bleeding during the menstrual period (Question 1), passing blood clots during the menstrual period (Question 2), and feeling tightness or pressure in the pelvic area (Question 5). Raw scores were transformed to a normalized score, with a range of possible scores from 0 to 100 (none of time, a little of time, some of the time, most of the time, and all of the time), where higher scores values are indicative of greater distress and lower scores are indicative of minimal distress. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.
Change From Pivotal Study Baseline In Uterine Volume At Week 52 Week 52 Volume of the uterus was measured by transvaginal or transabdominal ultrasound. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.
Change From Pivotal Study Baseline In Uterine Fibroid Volume At Week 52 Week 52 Volume of the primary uterine fibroid was measured by transvaginal or transabdominal ultrasound. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.
Percent Change From Pivotal Study Baseline In Bone Mineral Density (BMD) At The Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At Week 52 Week 52 Assessed by dual-energy X-ray absorptiometry (DXA) scan at the lumbar spine (L1-L4), total hip, and femoral neck at pivotal study Baseline and at Week 52. The scans were read by the central radiology laboratory in accordance with the imaging charter. The same DXA machine was used at the local imaging center at each site and operated in the same scan mode for all images procured for an individual participant. All images were submitted for central reading. The central radiology laboratory collected and evaluated all DXA scans for acceptability and measured BMD. The LS mean was derived for each treatment group using a mixed-effects model with repeated measure.
Change From Pivotal Study Baseline In Predose Serum E2 Concentrations At Week 52 Week 52 Blood samples were collected from participants at predose for E2 measurements. These were analyzed at a central laboratory.
Percentage Of Participants Who Achieved Or Maintained Amenorrhea Over The Last 35 Days Of Treatment Week 24 up to last 35 days of treatment (up to Week 52) Amenorrhea was defined as meeting 1 of the following criteria for 2 consecutive visits:
* No feminine product returned due to reported amenorrhea;
* No feminine product returned due to reports of spotting/negligible bleeding coupled with other data (participant's paper diary) indicating infrequent non-cyclic bleeding/spotting; and
* Feminine product collection with a negligible observed MBL volume coupled with data (participant's paper diary) indicating infrequent non-cyclic bleeding/spotting.Number Of Participants With Hemoglobin Increase Of ≥1 g/dL From Pivotal Study Baseline At Week 52 Among Those With A Hemoglobin Concentration Below Lower Limit Of Normal At Pivotal Baseline Week 52 Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin concentration below the lower limit of normal (11.6 g/dL) at pivotal study Baseline and reported at Week 52.
Percentage Of Participants With A Hemoglobin Level ≤10.5 Gram/Deciliter (g/dL) At Pivotal Study Baseline Who Achieved An Increase Of >2 g/dL From Pivotal Study Baseline At Week 52 Week 52 Blood samples were collected from participants for hemoglobin measurements. Percentages are based on number of participants with hemoglobin ≤10.5 g/dL at pivotal study Baseline and reported at Week 52.
Trial Locations
- Locations (129)
Andalusia
🇺🇸Andalusia, Alabama, United States
Birmingham
🇺🇸Birmingham, Alabama, United States
Mobile
🇺🇸Mobile, Alabama, United States
Mesa
🇺🇸Mesa, Arizona, United States
Tucson
🇺🇸Tucson, Arizona, United States
Little Rock
🇺🇸Little Rock, Arkansas, United States
Canoga Park
🇺🇸Canoga Park, California, United States
Huntington Beach
🇺🇸Huntington Beach, California, United States
La Mesa
🇺🇸La Mesa, California, United States
Long Beach
🇺🇸Long Beach, California, United States
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