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LIBERTY 1: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03049735
Recruitment Status : Active, not recruiting
First Posted : February 10, 2017
Last Update Posted : June 23, 2020
Sponsor:
Information provided by (Responsible Party):
Myovant Sciences GmbH

Tracking Information
First Submitted Date  ICMJE February 8, 2017
First Posted Date  ICMJE February 10, 2017
Last Update Posted Date June 23, 2020
Actual Study Start Date  ICMJE April 26, 2017
Actual Primary Completion Date April 29, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2020)
Percentage Of Participants Who Achieve A Menstrual Blood Loss (MBL) Volume Of < 80 mL And A ≥ 50% Reduction From Baseline MBL Volume Over The Last 35 Days Of Treatment [ Time Frame: From Baseline up to the last 35 days of treatment (up to 24 weeks) ]
MBL volume is measured using the alkaline hematin method. For the primary analysis, the Relugolix plus E2/NETA group (Group A) will be compared with the Placebo group (Group C). Comparison of Relugolix plus Delayed E2/NETA group (Group A) with the Placebo group (Group C) will be a secondary analysis.
Original Primary Outcome Measures  ICMJE
 (submitted: February 8, 2017)
Menstrual blood loss volume Group A vs Group C [ Time Frame: 24 weeks ]
Proportion of women in the relugolix Group A versus the placebo Group C who achieve a menstrual blood loss volume of < 80 mL and a 50% reduction from baseline.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2020)
  • Percentage Of Participants With Amenorrhea (No Or Negligible Bleeding) Over The Last 35 Days Of Treatment [ Time Frame: From Baseline up to last 35 days of treatment (up to 24 weeks) ]
    Will be assessed using MBL volume measured using the alkaline hematin method and participant daily electronic diary (eDiary) data.
  • Percent Change From Baseline At Week 24 In MBL Volume [ Time Frame: Baseline, Week 24 ]
    MBL volume is measured using the alkaline hematin method.
  • Change From Baseline At Week 24 In Uterine Fibroid Symptom (UFS)-Quality of Life (QoL) Bleeding And Pelvic Discomfort Scale Score As Measured By The UFS-QoL Questions 1, 2, and 5 [ Time Frame: Baseline, Week 24 ]
    Will be assessed with 3 questions (each with a 5-point scale ranging from 'Not at all' to 'A very great deal') related to menstrual bleeding and pelvic tightness/pressure.
  • Percentage of Participants With A Hemoglobin Level ≤ 10.5 g/dL At Baseline Who Have An Increase In Hemoglobin > 2 g/dL From Baseline At Week 24 [ Time Frame: From Baseline up to Week 24 ]
    Blood samples will be collected from participants for hemoglobin measurements.
  • Percentage Of Participants With A Maximum Numerical Rating Scale (NRS) Score ≤ 1 For Uterine Fibroid-Associated Pain Over The Last 35 Days Of Treatment [ Time Frame: From Baseline up to the last 35 days of treatment (up to 24 weeks) ]
    Uterine fibroid-associated pain will be assessed with a daily eDiary using an NRS score (11-point scale) in a subset of participants with a maximum NRS score ≥ 4 for pain associated with uterine fibroids during the last 35 days prior to randomization and at least 28 days with e-Diary entries of the last 35 days of treatment.
  • Percent Change From Baseline At Week 24 In Primary Uterine Fibroid Volume [ Time Frame: Baseline, Week 24 ]
    Volume of the primary uterine fibroid will be measured by transvaginal or transabdominal ultrasound.
  • Percent Change From Baseline At Week 24 In Uterine Volume [ Time Frame: Baseline, Week 24 ]
    Volume of the uterus will be measured by transvaginal or transabdominal ultrasound.
  • Time To MBL Response [ Time Frame: From Baseline through Week 24 ]
    Defined as the time to achieve an MBL volume of < 80 mL and a ≥ 50% reduction from baseline MBL volume as measured by the alkaline hematin method.
  • Change From Baseline At Week 24 In Impact On QoL, Assessed Using The UFS-QoL Questionnaire [ Time Frame: Baseline, Week 24 ]
  • Change From Baseline At Week 24 In Symptoms Assessed Using The Patient Global Assessment (PGA) Questionnaire [ Time Frame: Baseline, Week 24 ]
    The PGA for symptoms is a 1-item questionnaire designed to assess participant's impression of the severity of their symptoms related to uterine fibroids.
  • Change From Baseline At Week 24 In Function Assessed Using The PGA Questionnaire [ Time Frame: Baseline, Week 24 ]
    The PGA for function is a 1-item questionnaire designed to assess participant's impression of how their symptoms related to uterine fibroids affected their usual activities.
  • Percent Change From Baseline At Week 12 In Bone Mineral Density At The Lumbar Spine (L1 - L4) [ Time Frame: Baseline, Week 12 ]
    Assessed by a dual-energy X-ray absorptiometry (DXA) scan.
  • Percent Change From Baseline At Week 24 In Bone Mineral Density At The Lumbar Spine (L1 - L4), Total Hip, And Femoral Neck [ Time Frame: Baseline, Week 24 ]
    Assessed by a DXA scan.
  • Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 12 [ Time Frame: From Baseline through Week 12 ]
  • Percentage Of Participants Experiencing Vasomotor Symptoms Through Week 24 [ Time Frame: From Baseline through Week 24 ]
  • Predose Trough Concentrations Of Relugolix And NETA In The Relugolix Plus E2/NETA Group At Week 24 [ Time Frame: Week 24 ]
    Blood samples for determination of relugolix and NETA plasma concentrations will be collected for measurements.
  • Predose Trough Concentrations Of E2 In The Relugolix Plus E2/NETA Group At Week 24 [ Time Frame: Week 24 ]
    Blood samples for determination of E2 plasma concentrations will be collected for measurements.
  • Change In Serum Concentrations Of Luteinizing Hormone, Follicle-stimulating Hormone, Estradiol, And Progesterone [ Time Frame: Up to 24 weeks ]
    Blood samples will be collected from participants for hormonal measurements.
  • Percent Change From Baseline At Weeks 4, 8, 12, 16, And 20 In MBL Volume [ Time Frame: Baseline to Weeks 4, 8, 12, 16, and 20 ]
  • Time To Achieve An MBL Volume Of < 80 mL And At Least A 50% Reduction From Baseline MBL Volume [ Time Frame: From Baseline through Week 24 ]
    MBL volume is measured using the alkaline hematin method.
  • Percentage Of Participants In The Relugolix Plus E2/NETA Group Versus The Placebo Group Who Achieve An MBL Volume Of < 80 mL And At Least A 50% Reduction From Baseline MBL Volume By Visit [ Time Frame: From Baseline through Week 24 ]
  • Sustained Amenorrhea Rate (No Or Negligible Bleeding) By Visit [ Time Frame: From Baseline through Week 24 ]
  • Time To Achieving Sustained Amenorrhea (No Or Negligible Bleeding) [ Time Frame: From Baseline through Week 24 ]
  • Time To Achieving Amenorrhea (No Or Negligible Bleeding) [ Time Frame: From Baseline through Week 24 ]
  • Percentage Of Participants With A Hemoglobin Concentration Below The Lower Limit Of Normal At Baseline Who Achieve An Increase Of ≥ 1 g/dL From Baseline At Week 24 [ Time Frame: From Baseline through Week 24 ]
  • Change From Baseline At Week 24 In Hemoglobin For Participants With A Hemoglobin Concentration ≤ 10.5 g/dL At Baseline [ Time Frame: Baseline, Week 24 ]
  • Change From Baseline At Week 24 In The UFS-QoL Symptom Severity Scale Score [ Time Frame: Baseline, Week 24 ]
  • Change From Baseline At Week 24 In The UFS-QoL Activities Scale Score [ Time Frame: Baseline, Week 24 ]
  • Change From Baseline At Week 24 In The UFS-QoL Revised Activities Scale Score [ Time Frame: Baseline, Week 24 ]
  • Proportion Of Responders Who Achieve A Meaningful Increase Of At Least 20 Points From Baseline At Week 24 In UFS-QoL Revised Activities Scale Score [ Time Frame: From Baseline through Week 24 ]
  • Proportion Of Responders Who Achieve A Meaningful Reduction Of At Least 20 Points From Baseline At Week 24 In UFS-QoL Bleeding And Pelvic Discomfort Scale Score [ Time Frame: From Baseline through Week 24 ]
  • Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Physical Activities Based On UFS-QoL Question 11 [ Time Frame: Baseline, Week 24 ]
  • Change From Baseline At Week 24 In The Interference Of Uterine Fibroids With Social Activities Based On UFS-QoL Question 20 [ Time Frame: Baseline, Week 24 ]
  • Change From Baseline At Week 24 In Embarrassment Caused By Uterine Fibroids Based On UFS-QoL Question 29 [ Time Frame: Baseline, Week 24 ]
  • Participants Achieving Improvement From Baseline In PGA For UFS From Baseline At Week 24 [ Time Frame: From Baseline through Week 24 ]
  • Participants Achieving Improvement From Baseline In PGA For Uterine Fibroid-related Function From Baseline At Week 24 [ Time Frame: From Baseline through Week 24 ]
  • Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Physical Activities [ Time Frame: Baseline, Week 24 ]
  • Change From Baseline At Week 24 In The Menorrhagia Impact Questionnaire Score For Social And Leisure Activities [ Time Frame: Baseline, Week 24 ]
  • Participants Who Achieve A Maximum NRS Score For Pain Associated With Uterine Fibroids Over The Last 35 Days Of Treatment [ Time Frame: From Baseline up to the last 35 days of treatment (up to 24 weeks) ]
    The maximum NRS score should be at least a 30% reduction from baseline in the subset of participants with a maximum pain score ≥ 4 during the 35 days prior to randomization.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2017)
Menstrual blood loss volume Group B vs Group C [ Time Frame: 24 weeks ]
Proportion of women in the relugolix Group B versus the placebo Group C who achieve a menstrual blood loss volume of < 80 mL and a 50% reduction from baseline.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE LIBERTY 1: Efficacy & Safety Study of Relugolix in Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
Official Title  ICMJE LIBERTY 1: 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
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 women 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Heavy Menstrual Bleeding
  • Uterine Fibroid
Intervention  ICMJE
  • Drug: Relugolix
    Relugolix (40 mg) tablet administered orally once daily.
    Other Names:
    • TAK-385
    • MVT-601
  • Drug: Estradiol/norethindrone acetate
    E2 (1.0 mg)/NETA (0.5 mg) co-formulated capsule administered orally once daily.
    Other Names:
    • E2/NETA
    • low-dose hormonal add-back
  • Drug: Estradiol/norethindrone acetate placebo
    E2 (0 mg)/NETA (0 mg) placebo capsule administered orally once daily and designed to match the capsule containing E2/NETA in size, shape, color, and odor.
  • Drug: Relugolix placebo
    Relugolix (0 mg) placebo tablet administered orally once daily and manufactured to match the relugolix tablet in size, shape, color, and odor.
Study Arms  ICMJE
  • Experimental: Relugolix plus E2/NETA (Group A)
    Relugolix co-administered with E2/NETA for 24 weeks.
    Interventions:
    • Drug: Relugolix
    • Drug: Estradiol/norethindrone acetate
  • Experimental: Relugolix plus Delayed E2/NETA (Group B)
    Relugolix co-administered with E2/NETA placebo for 12 weeks, followed by relugolix co-administered with E2/NETA for 12 weeks.
    Interventions:
    • Drug: Relugolix
    • Drug: Estradiol/norethindrone acetate
    • Drug: Estradiol/norethindrone acetate placebo
  • Placebo Comparator: Placebo (Group C)
    Relugolix placebo co-administered with E2/NETA placebo for 24 weeks.
    Interventions:
    • Drug: Estradiol/norethindrone acetate placebo
    • Drug: Relugolix placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 16, 2020)
388
Original Estimated Enrollment  ICMJE
 (submitted: February 8, 2017)
390
Estimated Study Completion Date  ICMJE December 31, 2020
Actual Primary Completion Date April 29, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 patient'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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Italy,   Poland,   South Africa,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03049735
Other Study ID Numbers  ICMJE MVT-601-3001
2016-003727-27 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Myovant Sciences GmbH
Study Sponsor  ICMJE Myovant Sciences GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Myovant Medical Monitor Myovant Sciences
PRS Account Myovant Sciences GmbH
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP