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CompletedNCT03412890Updated May 9, 2024Results posted

LIBERTY EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

A Phase 3 interventional study of Relugolix and Estradiol/norethindrone acetate in Heavy Menstrual Bleeding and Uterine Fibroid, sponsored by Myovant Sciences GmbH. Completed at 150 sites in 9 countries. Open to female participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2024-05-09.

Sponsored by Myovant Sciences GmbH · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
477
Allocation
Not applicable
Ages
18 Years to 50 Years
Sex
Female
01

Study 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).

Read the 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.

02

Conditions studied

  • Heavy Menstrual Bleeding
  • Uterine Fibroid

Keywords

  • Uterine Fibroid
  • Heavy Menstrual Bleeding
  • Menstrual Blood Volume
03

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  1. Completed 24 weeks of study drug treatment and study participation in either pivotal study, MVT-601-3001 or MVT-601-3002

Key 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 pivotal study (MVT-601-3001 or MVT-601-3002)
  2. Met a withdrawal criterion in the pivotal study (MVT-601-3001 or MVT-601-3002).
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
477 participants (actual)

Study arms

  • Experimental
    Relugolix plus E2/NETA

    Relugolix co-administered with E2/NETA for 28 weeks.

    Drug: Relugolix · Drug: Estradiol/norethindrone acetate

Interventions

  • DrugRelugolix

    Relugolix 40-mg tablet administered orally once daily

    Also known as: MVT-601, TAK-385

  • DrugEstradiol/norethindrone acetate

    Capsule containing co-formulated tablet of E2 (1 mg) and NETA (0.5 mg) administered orally once daily

    Also known as: E2/NETA

05

What researchers measure

Primary outcomes

  1. 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

    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.

    Time frame: Week 52/End of Treatment

Secondary outcomes

  1. Change From Pivotal Study Baseline In MBL Volume At 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.

    Time frame: Week 52

  2. Percentage Of Participants Who Achieved Or Maintained Amenorrhea Over The Last 35 Days Of Treatment

    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.

    Time frame: Week 24 up to last 35 days of treatment (up to Week 52)

  3. 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

    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.

    Time frame: Week 52

  4. 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

    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.

    Time frame: Week 52

  5. Change From Pivotal Study Baseline In Hemoglobin Concentration At 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.

    Time frame: Week 52

  6. Change From Pivotal Study Baseline In The UFS-QoL Symptom Severity Scale At 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.

    Time frame: Week 52

  7. Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At 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.

    Time frame: Week 52

  8. Change From Pivotal Study Baseline In The UFS-QoL Score By Health-Related Quality of Life Total Score At 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.

    Time frame: Week 52

  9. 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

    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.

    Time frame: Week 52

  10. Change From Pivotal Study Baseline In Uterine Volume At 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.

    Time frame: Week 52

  11. Change From Pivotal Study Baseline In Uterine Fibroid Volume At 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.

    Time frame: Week 52

  12. 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

    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.

    Time frame: Week 52

  13. Change From Pivotal Study Baseline In Predose Serum E2 Concentrations At Week 52

    Blood samples were collected from participants at predose for E2 measurements. These were analyzed at a central laboratory.

    Time frame: Week 52

Other outcomes

  1. Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52

    The EQ-5D-5L scale is a standardized instrument for use as a measure of health outcomes. Mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were each assessed on 5-point categorical scales of no problems to unable to complete specified activity, or no pain/discomfort to extreme pain/discomfort, or not anxious/depressed to extremely anxious/depressed. The change from baseline is summarized by amount of improvement (1-4 categories), amount of deterioration (1-4 categories), or no change.

    Time frame: Week 52

06

Results

Posted May 9, 2024

Participant flow

All participants who completed their participation in one of the pivotal studies (MVT-601-3001 or MVT-601-3002) were eligible to enroll in this study.

Participant flow — Overall Study
MilestoneRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Started163150164
Received at least 1 dose of study drug163149164
Completed133108122
Not completed304242
Withdrew: Adverse event559
Withdrew: Protocol deviation212
Withdrew: Lost to follow-up71010
Withdrew: Withdrawal by subject91211
Withdrew: Lack of efficacy275
Withdrew: Other565
Withdrew: Participants who did not receive any study drug010

Outcome measures

PrimaryPercentage 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

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.

Time frame:
Week 52/End of Treatment
Reported as:
Number · percentage of participants
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
percentage of participantsRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
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 Treatment86.50 (80.28 to 91.34)79.87 (72.52 to 85.98)75.00 (67.65 to 81.42)
SecondaryChange From Pivotal Study Baseline In MBL Volume At 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.

Time frame:
Week 52
Reported as:
Least squares mean · mL
Change From Pivotal Study Baseline In MBL Volume At Week 52
mLRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Change From Pivotal Study Baseline In MBL Volume At Week 52-251.6 ± 16.38-219.1 ± 13.91-204.7 ± 13.31
SecondaryPercentage Of Participants Who Achieved Or Maintained Amenorrhea Over The Last 35 Days Of Treatment

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.

Time frame:
Week 24 up to last 35 days of treatment (up to Week 52)
Reported as:
Number · percentage of participants
Percentage Of Participants Who Achieved Or Maintained Amenorrhea Over The Last 35 Days Of Treatment
percentage of participantsRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Percentage Of Participants Who Achieved Or Maintained Amenorrhea Over The Last 35 Days Of Treatment70.55 (62.92 to 77.42)68.46 (60.35 to 75.82)57.93 (49.98 to 65.58)
SecondaryPercentage 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

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.

Time frame:
Week 52
Reported as:
Number · percentage of participants
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
percentage of participantsRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
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 5258.97 (42.10 to 74.43)78.95 (62.68 to 90.45)42.11 (26.31 to 59.18)
SecondaryNumber 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

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.

Time frame:
Week 52
Reported as:
Number · participants
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
participantsRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
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 Baseline566045
SecondaryChange From Pivotal Study Baseline In Hemoglobin Concentration At 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.

Time frame:
Week 52
Reported as:
Least squares mean · g/dL
Change From Pivotal Study Baseline In Hemoglobin Concentration At Week 52
g/dLRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Change From Pivotal Study Baseline In Hemoglobin Concentration At Week 522.7 ± 0.243.0 ± 0.231.9 ± 0.22
SecondaryChange From Pivotal Study Baseline In The UFS-QoL Symptom Severity Scale At 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.

Time frame:
Week 52
Reported as:
Least squares mean · score on a scale
Change From Pivotal Study Baseline In The UFS-QoL Symptom Severity Scale At Week 52
score on a scaleRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Change From Pivotal Study Baseline In The UFS-QoL Symptom Severity Scale At Week 52-37.3 ± 2.47-38.2 ± 2.77-35.0 ± 2.48
SecondaryChange From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At 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.

Time frame:
Week 52
Reported as:
Least squares mean · score on a scale
Change From Pivotal Study Baseline In The UFS-QoL Score Health-Related Quality of Life Subscales Score At Week 52
score on a scaleRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Concern56.4 ± 2.9256.4 ± 3.1051.2 ± 3.10
Activities47.8 ± 2.7246.9 ± 2.8245.2 ± 2.81
Revised activities49.2 ± 2.7848.0 ± 2.9746.9 ± 2.85
Energy/mood35.6 ± 2.6738.6 ± 2.8836.5 ± 2.79
Control33.0 ± 2.6936.4 ± 2.8232.2 ± 2.91
Self-conscious31.2 ± 3.0635.4 ± 3.4031.0 ± 3.14
Sexual function22.7 ± 3.4022.0 ± 3.8724.1 ± 3.62
SecondaryChange From Pivotal Study Baseline In The UFS-QoL Score By Health-Related Quality of Life Total Score At 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.

Time frame:
Week 52
Reported as:
Least squares mean · score on a scale
Change From Pivotal Study Baseline In The UFS-QoL Score By Health-Related Quality of Life Total Score At Week 52
score on a scaleRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Change From Pivotal Study Baseline In The UFS-QoL Score By Health-Related Quality of Life Total Score At Week 5240.4 ± 2.5041.7 ± 2.6839.0 ± 2.63
SecondaryChange 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

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.

Time frame:
Week 52
Reported as:
Least squares mean · score on a scale
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
score on a scaleRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
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 52-51.3 ± 2.66-51.6 ± 3.11-48.6 ± 2.76
SecondaryChange From Pivotal Study Baseline In Uterine Volume At 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.

Time frame:
Week 52
Reported as:
Least squares mean · cm^3
Change From Pivotal Study Baseline In Uterine Volume At Week 52
cm^3Relugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Change From Pivotal Study Baseline In Uterine Volume At Week 52-73.31 ± 14.471-91.67 ± 20.143-37.62 ± 14.541
SecondaryChange From Pivotal Study Baseline In Uterine Fibroid Volume At 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.

Time frame:
Week 52
Reported as:
Least squares mean · cm^3
Change From Pivotal Study Baseline In Uterine Fibroid Volume At Week 52
cm^3Relugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Change From Pivotal Study Baseline In Uterine Fibroid Volume At Week 52-31.84 ± 5.353-28.18 ± 5.523-17.07 ± 5.726
SecondaryPercent Change From Pivotal Study Baseline In Bone Mineral Density (BMD) At The Lumbar Spine (L1-L4), Femoral Neck, And Total Hip At 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.

Time frame:
Week 52
Reported as:
Least squares mean · percentage change
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
percentage changeRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Lumbar Spine (L1-L4)-0.804 ± 0.2803-2.045 ± 0.2679-0.775 ± 0.2781
Total Hip-0.153 ± 0.2337-0.842 ± 0.2308-0.065 ± 0.2086
Femoral Neck-0.575 ± 0.3208-0.513 ± 0.45030.004 ± 0.3886
SecondaryChange From Pivotal Study Baseline In Predose Serum E2 Concentrations At Week 52

Blood samples were collected from participants at predose for E2 measurements. These were analyzed at a central laboratory.

Time frame:
Week 52
Reported as:
Mean · pg/mL
Change From Pivotal Study Baseline In Predose Serum E2 Concentrations At Week 52
pg/mLRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Change From Pivotal Study Baseline In Predose Serum E2 Concentrations At Week 52-21.83 ± 91.525-33.77 ± 106.407-29.99 ± 81.465
Other pre-specifiedChange From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52

The EQ-5D-5L scale is a standardized instrument for use as a measure of health outcomes. Mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were each assessed on 5-point categorical scales of no problems to unable to complete specified activity, or no pain/discomfort to extreme pain/discomfort, or not anxious/depressed to extremely anxious/depressed. The change from baseline is summarized by amount of improvement (1-4 categories), amount of deterioration (1-4 categories), or no change.

Time frame:
Week 52
Reported as:
Count of participants · Participants
Change From Pivotal Study Baseline In European Quality Of Life Five Dimension Five Level (EQ-5D-5L) Scale At Week 52
ParticipantsRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Mobility - 4 Category deterioration000
Mobility - 3 Category deterioration010
Mobility - 2 Category deterioration200
Mobility - 1 Category deterioration354
Mobility - No change1028999
Mobility - 1 Category improvement15910
Mobility - 2 Category improvement534
Mobility - 3 Category improvement010
Mobility - 4 Category improvement000
Self-care - 4 Category deterioration000
Self-care - 3 Category deterioration000
Self-care - 2 Category deterioration010
Self-care - 1 Category deterioration112
Self-care - No change122105108
Self care - 1 Category improvement305
Self care - 2 Category improvement111
Self care - 3 Category improvement000
Self care - 4 Category improvement001
Usual activities - 4 Category deterioration000
Usual activities - 3 Category deterioration010
Usual activities - 2 Category deterioration302
Usual activities - 1 Category deterioration424
Usual activities - No change917173
Usual activities - 1 Category improvement152222
Usual activities - 2 Category improvement101012
Usual activities - 3 Category improvement323
Usual activities - 4 Category improvement101
Pain/discomfort - 4 Category deterioration000
Pain/discomfort - 3 Category deterioration012
Pain/discomfort - 2 Category deterioration320
Pain/discomfort - 1 Category deterioration17810
Pain/discomfort - No change464545
Pain/discomfort - 1 Category improvement373137
Pain/discomfort - 2 Category improvement161417
Pain/discomfort - 3 Category improvement866
Pain/discomfort - 4 Category improvement010
Anxiety/depression - 4 Category deterioration001
Anxiety/depression - 3 Category deterioration000
Anxiety/depression - 2 Category deterioration435
Anxiety/depression - 1 Category deterioration112012
Anxiety/depression - No change795369
Anxiety/depression - 1 Category improvement242517
Anxiety/depression - 2 Category improvement8711
Anxiety/depression - 3 Category improvement001
Anxiety/depression - 4 Category improvement101

Adverse events

Collected over Week 24 up to Week 52. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Relugolix Plus E2/NETA (Group A)0/163 (0%)1/163 (0.6%)22/163 (13.5%)
Relugolix Plus Delayed E2/NETA (Group B)0/149 (0%)5/149 (3.4%)12/149 (8.1%)
Placebo (Group C)0/164 (0%)11/164 (6.7%)38/164 (23.2%)
Most frequent serious events
Showing 10 of 18
Most frequent serious events
EventRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
AppendicitisInfections and infestations0/1630/1492/164
MenorrhagiaReproductive system and breast disorders0/1630/1492/164
CholecystitisHepatobiliary disorders0/1631/1490/164
CholelithiasisHepatobiliary disorders0/1631/1490/164
Ankle fractureInjury, poisoning and procedural complications0/1631/1490/164
Forearm fractureInjury, poisoning and procedural complications0/1631/1490/164
Wrist fractureInjury, poisoning and procedural complications0/1631/1490/164
Uterine leiomyomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1631/1490/164
Uterine haemorrhageReproductive system and breast disorders1/1630/1490/164
AnaemiaBlood and lymphatic system disorders0/1630/1491/164
Most frequent other events
Most frequent other events
EventRelugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)
Hot flushVascular disorders4/1630/14913/164
HeadacheNervous system disorders6/1637/14911/164
NasopharyngitisInfections and infestations10/1633/1498/164
HypertensionVascular disorders2/1633/14910/164

Baseline characteristics

Extension Safety Population: all enrolled participants who received any amount of open-label study drug in the open-label extension study.

Age, Continuous
Age, Continuous(years)Relugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)Total
Mean42.6 ± 5.0842.1 ± 5.5841.9 ± 5.4342.2 ± 5.36
Sex: Female, Male
Sex: Female, Male(Participants)Relugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)Total
Female163149164476
Male0000
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Relugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)Total
Hispanic or Latino383436108
Not Hispanic or Latino122113126361
Unknown or Not Reported3227
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Relugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)Total
American Indian or Alaska Native27110
Asian0303
Black or African American698188238
Native Hawaiian or Other Pacific Islander0000
White855171207
Other2327
Multiple2215
Not Reported3216
Region of Enrollment
Region of Enrollment(participants)Relugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)Total
United States113104117335
Belgium0314
Brazil46212
Chile56819
Czechia4228
Hungary64717
Italy75315
Poland14141947
South Africa105520
Mean Menstrual Blood Loss (MBL) volume
Mean Menstrual Blood Loss (MBL) volume(mL)Relugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)Total
Mean248.71 ± 196.694238.78 ± 155.332216.01 ± 123.786234.33 ± 161.753
Body Mass Index
Body Mass Index(kg/m^2)Relugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)Total
Mean31.384 ± 7.047030.997 ± 6.400032.577 ± 7.455631.675 ± 7.0162
Bone Mineral Density (BMD)
Bone Mineral Density (BMD)(g/cm^2)Relugolix Plus E2/NETA (Group A)Relugolix Plus Delayed E2/NETA (Group B)Placebo (Group C)Total
Lumbar Spine (L1-L4)1.186 ± 0.15991.225 ± 0.17301.239 ± 0.15731.217 ± 0.1645
Total Hip1.044 ± 0.13821.062 ± 0.14631.069 ± 0.14011.058 ± 0.1415
Femoral Neck0.960 ± 0.15720.994 ± 0.16570.994 ± 0.16480.982 ± 0.1630
07

Study locations

150 sites
  • Andalusia
    Andalusia, Alabama 36420, United States
  • Birmingham
    Birmingham, Alabama 35205, United States
  • Mobile
    Mobile, Alabama 36608, United States
  • Mesa
    Mesa, Arizona 85209, United States
  • Tucson
    Tucson, Arizona 85712, United States
  • Little Rock
    Little Rock, Arkansas 72204, United States
  • Canoga Park
    Canoga Park, California 91303, United States
  • Huntington Beach
    Huntington Beach, California 92647, United States
  • La Mesa
    La Mesa, California 91942, United States
  • Long Beach
    Long Beach, California 90806, United States
  • Los Angeles
    Los Angeles, California 90036, United States
  • Los Angeles
    Los Angeles, California 90057, United States
  • Norwalk
    Norwalk, California 90650, United States
  • Panorama
    Panorama City, California 91402, United States
  • San Diego
    San Diego, California 92108, United States
  • San Diego
    San Diego, California 92111, United States
  • Denver
    Denver, Colorado 80209, United States
  • Lakewood
    Lakewood, Colorado 80228, United States
  • Washington
    Washington, District of Columbia 20036, United States
  • Aventura
    Aventura, Florida 33180, United States
  • Clearwater
    Clearwater, Florida 33759, United States
  • DeLand
    DeLand, Florida 32720, United States
  • Ft. Lauderdale
    Fort Lauderdale, Florida 33316, United States
  • Fort Myers
    Fort Myers, Florida 33912, United States
  • Hialeah
    Hialeah, Florida 33016, United States
  • Jacksonville
    Jacksonville, Florida 32207, United States
  • Jupiter
    Jupiter, Florida 33458, United States
  • Loxahatchee
    Loxahatchee Groves, Florida 33470, United States
  • Margate
    Margate, Florida 33063, United States
  • Miami
    Miami, Florida 33126, United States
  • Miami
    Miami, Florida 33155, United States
  • Miami
    Miami, Florida 33165, United States
  • New Port Richey
    New Port Richey, Florida 34652, United States
  • Orlando
    Orlando, Florida 32808, United States
  • Oviedo
    Oviedo, Florida 32765, United States
  • Palm Harbor
    Palm Harbor, Florida 34684, United States
  • Saint Cloud
    Saint Cloud, Florida 34769, United States
  • Sarasota
    Sarasota, Florida 34239, United States
  • Tampa
    Tampa, Florida 33606, United States
  • Tampa
    Tampa, Florida 33613, United States
  • West Palm Beach
    West Palm Beach, Florida 33409, United States
  • Weston
    Weston, Florida 33327, United States
  • Atlanta
    Atlanta, Georgia 30342, United States
  • Atlanta
    Atlanta, Georgia 30363, United States
  • Augusta
    Augusta, Georgia 30904, United States
  • College Park
    College Park, Georgia 30349, United States
  • Decatur
    Decatur, Georgia 30034, United States
  • Duluth
    Duluth, Georgia 30097, United States
  • Norcross
    Norcross, Georgia 30093, United States
  • Savannah
    Savannah, Georgia 31406, United States
  • Chicago
    Chicago, Illinois 60611, United States
  • Naperville
    Naperville, Illinois 60540, United States
  • Oakbrook
    Oakbrook Terrace, Illinois 60523, United States
  • Shawnee
    Shawnee Mission, Kansas 66218, United States
  • Covington
    Covington, Louisiana 70433, United States
  • Marrero
    Marrero, Louisiana 70072, United States
  • Metairie
    Metairie, Louisiana 70001, United States
  • Metairie
    Metairie, Louisiana 70006, United States
  • Baltimore
    Baltimore, Maryland 21208, United States
  • Towson
    Towson, Maryland 21204, United States
  • Canton
    Canton, Michigan 48187, United States
  • Detroit
    Detroit, Michigan 48201, United States
  • Saginaw
    Saginaw, Michigan 48604, United States
  • Lincoln
    Lincoln, Nebraska 68510, United States
  • Las Vegas
    Las Vegas, Nevada 89109, United States
  • Las Vegas
    Las Vegas, Nevada 89113, United States
  • Las Vegas
    Las Vegas, Nevada 89128, United States
  • Lawrenceville
    Lawrenceville, New Jersey 08648, United States
  • Albuquerque
    Albuquerque, New Mexico 87102, United States
  • Brooklyn
    Brooklyn, New York 11201, United States
  • New York
    New York, New York 10022, United States
  • Williamsville
    Williamsville, New York 14221, United States
  • Durham
    Durham, North Carolina 27713, United States
  • Raleigh
    Raleigh, North Carolina 27607, United States
  • Raleigh
    Raleigh, North Carolina 27612, United States
  • Winston-Salem
    Winston-Salem, North Carolina 27103, United States
  • Cincinnati
    Cincinnati, Ohio 45212, United States
  • Cincinnati
    Cincinnati, Ohio 45219, United States
  • Columbus
    Columbus, Ohio 43231, United States
  • Englewood
    Englewood, Ohio 45322, United States
  • Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • Bluffton
    Bluffton, South Carolina 29910, United States
  • Charleston
    Charleston, South Carolina 29406, United States
  • Columbia
    Columbia, South Carolina 29201, United States
  • Chattanooga
    Chattanooga, Tennessee 37404, United States
  • Memphis
    Memphis, Tennessee 38119, United States
  • Memphis
    Memphis, Tennessee 38120, United States
  • Beaumont
    Beaumont, Texas 77702, United States
  • Dallas
    Dallas, Texas 75231, United States
  • Fort Worth
    Fort Worth, Texas 76104, United States
  • Houston
    Houston, Texas 77030, United States
  • Houston
    Houston, Texas 77054, United States
  • Houston
    Houston, Texas 77074, United States
  • Longview
    Longview, Texas 75605, United States
  • San Antonio
    San Antonio, Texas 78229, United States
  • San Antonio
    San Antonio, Texas 78258, United States
  • Sugar Land
    Sugar Land, Texas 77479, United States
  • Webster
    Webster, Texas 77598, United States
  • Salt Lake City
    Salt Lake City, Utah 84107, United States
  • Salt Lake City
    Salt Lake City, Utah 84124, United States

Showing the first 100 of 150 sites across 9 countries.

08

References and documents

Publications

  • 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. PubMed 36357960 ↗

Study documents

  • Study protocol · Oct 18, 2018
  • Statistical analysis plan · Jan 31, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03412890
Lead sponsor
Myovant Sciences GmbH
Responsible party
Sponsor
First posted
Jan 29, 2018
Start date
Oct 19, 2017
Primary completion
Jan 21, 2020
Completion
Jan 13, 2021
Results posted
May 9, 2024
Last update
May 9, 2024

Study contacts

Myovant Medical Monitor
study director · Myovant Sciences

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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