Study of the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are at Risk for Pregnancy (SERENE)

• ClinicalTrials.gov Identifier: NCT04756037
• Recruitment Status: Recruiting
• First Posted: February 16, 2021
• Last Update Posted: October 13, 2023
• Sponsor: Myovant Sciences GmbH
• Information provided by (Responsible Party): Myovant Sciences GmbH

Tracking Information

• First Submitted Date: February 12, 2021
• First Posted Date: February 16, 2021
• Last Update Posted Date: October 13, 2023
• Actual Study Start Date: March 18, 2021
• Estimated Primary Completion Date: April 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 2, 2021)

Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the At-Risk Pearl Index (PI) [ Time Frame: 13 consecutive 28-day treatment cycles ]

The At-Risk PI is defined as the number of on treatment pregnancies per 100 women-years of treatment. The At-Risk PI will be calculated on the basis of cycles considered at-risk of pregnancy, that is, consecutive 28-day periods without use of any other contraceptive methods and with affirmed occurrence of vaginal intercourse. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.

Original Primary Outcome Measures (submitted: February 12, 2021)

Contraceptive Efficacy Of Relugolix Combination Therapy As Assessed By The At-Risk Pearl Index (PI) [ Time Frame: 13 consecutive 28-day treatment cycles ]

The At Risk PI is defined as the number of on treatment pregnancies per 100 women-years of treatment. The At-Risk PI will be calculated on the basis of cycles considered at-risk of pregnancy, that is, consecutive 28-day periods without use of any other contraceptive methods and with affirmed occurrence of vaginal intercourse. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.

Current Secondary Outcome Measures (submitted: September 2, 2021)

• Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Modified At-Risk PI [ Time Frame: 13 consecutive 28-day treatment cycles ]
  The Modified At-Risk PI is based on the number of on-treatment pregnancies occurring during cycles without any other contraceptive methods, regardless of occurrence of vaginal intercourse. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.
• Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Gross PI [ Time Frame: 13 consecutive 28-day treatment cycles ]
  The "typical use" contraceptive efficacy will be assessed using the Gross PI, based on the number of on-treatment pregnancies occurring during all cycles regardless of the use of other contraceptive methods, confirmed vaginal intercourse, or protocol compliance. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.
• Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Method Failure PI [ Time Frame: 13 consecutive 28-day treatment cycles ]
  The "perfect use" contraceptive efficacy will be assessed using the Method Failure PI, based on the number of on-treatment pregnancies occurring during cycles that are at risk and without major protocol deviations. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.
• Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Cumulative 1-Year Pregnancy Rates [ Time Frame: 13 consecutive 28-day treatment cycles ]
• Incidence of Treatment-Emergent Adverse Events [ Time Frame: 54 Weeks ]
• Number of Participants Who Do Not Complete 13 Treatment Cycles [ Time Frame: 13 consecutive 28-day treatment cycles ]
• Percent Change in Bone Mineral Density from Baseline to 6 and 12 Months On-Treatment [ Time Frame: 12 Months On-Treatment or EOT ]
  The percent change in bone mineral density will be measured from baseline to 6- and 12-months on treatment at the lumbar spine (L1-L4), total hip, and femoral neck.
• Percent Change in Bone Mineral Density from Baseline an 12 Months On-Treatment (or EOT) to 6 and 12 Months Post-Treatment [ Time Frame: 12 Months Post-Treatment Follow-Up ]
  The percent change in bone mineral density will be measured from baseline and 12-months on-treatment (or End-of-Treatment) to 6- and 12-months post-treatment at the lumbar spine (L1-L4), total hip, and femoral neck.

Original Secondary Outcome Measures (submitted: February 12, 2021)

• Contraceptive Efficacy Of Relugolix Combination Therapy As Assessed By The Modified At-Risk PI [ Time Frame: 13 consecutive 28-day treatment cycles ]
  The Modified At-Risk PI is based on the number of on-treatment pregnancies occurring during cycles without any other contraceptive methods, regardless of occurrence of vaginal intercourse. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.
• Contraceptive Efficacy Of Relugolix Combination Therapy As Assessed By The Gross PI [ Time Frame: 13 consecutive 28-day treatment cycles ]
  The "Typical use" contraceptive efficacy will be assessed using the Gross PI, based on the number of on-treatment pregnancies occurring during all cycles regardless of the use of other contraceptive methods, confirmed vaginal intercourse, or protocol compliance. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.
• Contraceptive Efficacy Of Relugolix Combination Therapy As Assessed By The Method Failure PI [ Time Frame: 13 consecutive 28-day treatment cycles ]
  The "Perfect use" contraceptive efficacy will be assessed using the Method Failure PI, based on the number of on-treatment pregnancies occurring during cycles that are at risk and without major protocol deviations. On-treatment pregnancies are pregnancies with an estimated conception date between the first day of study intervention intake up to and including 7 days after the last intake of study medication.
• Contraceptive Efficacy Of Relugolix Combination Therapy As Assessed By The Cumulative 1-year Pregnancy Rates [ Time Frame: 13 consecutive 28-day treatment cycles ]
• Incidence Of Treatment-emergent Adverse Events [ Time Frame: 54 Weeks ]
• Number Of Participants Who Do Not Complete 13 Treatment Cycles [ Time Frame: 13 consecutive 28-day treatment cycles ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are at Risk for Pregnancy
• Official Title: A Phase 3, Single-Arm, Open-Label Study to Evaluate the Safety and Contraceptive Efficacy of Relugolix Combination Therapy in Women With Uterine Fibroids or Endometriosis Who Are 18 to 50 Years of Age and at Risk for Pregnancy
• Brief Summary: The purpose of this study is to assess the contraceptive efficacy of relugolix combination therapy.
• Detailed Description: This is a single-arm, open-label, phase 3 study to assess the contraceptive efficacy of relugolix combination therapy (relugolix 40 milligrams [mg], estradiol [E2] 1 mg, and norethindrone acetate [NETA] 0.5 mg).
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Contraception

Intervention

Drug: Relugolix Combination Therapy

Participants will receive orally 1 fixed-dose combination tablet (relugolix 40 mg/E2 1 mg/NETA 0.5 mg) once daily.

Other Name: Myfembree

Study Arms

Experimental: Relugolix/E2/NETA

Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).

Intervention: Drug: Relugolix Combination Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 2, 2021): 1020
• Original Estimated Enrollment (submitted: February 12, 2021): 900
• Estimated Study Completion Date: April 2025
• Estimated Primary Completion Date: April 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Is a premenopausal woman, 18 to 50 years of age.
2. Is at risk of pregnancy (that is, having heterosexual intercourse at least once per month) and is seeking contraception.
3. Has normal, regular menstrual cycles that are between 21 and 35 days in duration.

4. Has a diagnosis of uterine fibroids or endometriosis meeting either of the following criteria:

   1. Diagnosis of uterine fibroids by confirmation of ultrasound performed in the last 2 years and patient report of heavy menstrual bleeding affecting quality of life.
   2. Diagnosis of endometriosis and has had surgical or direct visualization (laparoscopy or laparotomy) and/or histopathologic confirmation of endometriosis, and the patient reports moderate, severe, or very severe pain during the most recent menses and/or during nonmenstrual portion of the cycle in the prior month
5. Is willing to use the study intervention as the sole method of contraception for 13 consecutive 28-day treatment cycles and does not intend to use any other form of contraception (for example, condoms).

Key Exclusion Criteria:

1. Is pregnant, or breastfeeding, or has breastfed in the last year.
2. Has a known history of infertility or sub-fertility.
3. Has presence or history of a venous thromboembolic event (for example, deep vein thrombosis, pulmonary embolism), an arterial thrombotic or thromboembolic event (for example, myocardial infarction, stroke, or peripheral arterial), or a transient ischemic attack, angina pectoris, or claudication.
4. Has a higher risk of arterial, venous thrombotic, or thromboembolic disorders.
5. Has a history of migraine with aura or focal neurological symptoms.
6. Has uncontrolled hypertension, diabetes with inadequate control, or multiple cardiovascular risk factors.
7. Has a history of clinically significant ventricular arrhythmias.
8. Has clinically significant liver disease, including active viral hepatitis or cirrhosis.
9. Has a history of pancreatitis associated with severe hypertriglyceridemia.
10. Has known human immunodeficiency virus (HIV) infection or high risk of contracting HIV.
11. Has a hepatic hemangioma or has a history of cholestasis with prior estrogen use or during pregnancy.
12. Has a serious contraindication to pregnancy (for example, a medical condition or use of chronic medication such as isotretinoin or thalidomide).
13. History of suicidal ideation or behavior, or confirmed "yes" to any question (with exception of non-suicidal self-injurious behavior, unless deemed as an unacceptable risk by the investigator) on the C-SSRS.
14. Has a bone mineral density Z-score ≤ -2.0 at lumbar spine, femoral neck, or total hip during the screening period.
15. Has a history of or currently has osteoporosis, or other metabolic bone disease, collagen vascular disease, chronic kidney disease (CKD) stage 3 or greater with glomerular filtration rate (GFR) < 60 mL/min/m2 using Modification of Diet in Renal Disease (MDRD) method, hyperparathyroidism, hyperprolactinemia, known pituitary adenoma, hyperthyroidism, anorexia nervosa, abnormal bone mineral metabolism (eg, hypophosphatemia), or low traumatic (fragility) fracture.
16. Has used chronic glucocorticoids that are oral, parenteral, inhaled (prednisone equivalents of ≥ 2.5 mg daily for ≥ 3 months) in 12 months prior to the study.
17. Has known BRCA mutation or other mutation associated with increased risk of breast cancer.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials at Myovant; 650-278-8743; ClinicalTrials@Myovant.com

Contact: Myovant Medical Monitor Study Director

• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT04756037
• Other Study ID Numbers: MVT-601-050
• 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

• Plan to Share IPD: No

• Current Responsible Party: Myovant Sciences GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: Myovant Sciences GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Myovant Sciences GmbH
• Verification Date: October 2023