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)

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

The purpose of this study is to assess the contraceptive efficacy of relugolix combination therapy.

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: 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
• Enrollment (Actual): 1164
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Cidra, Puerto Rico, 00739
    • Cidra
  • San Juan, Puerto Rico, 00907
    • San Juan
  • San Juan, Puerto Rico, 00909
    • San Juan
• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • Mobile
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Chandler
    • Mesa, Arizona, United States, 85209
      • Mesa
    • Peoria, Arizona, United States, 85381
      • Peoria
    • Phoenix, Arizona, United States, 85020
      • Phoenix
  • California
    • Burbank, California, United States, 91506
      • Burbank
    • Canoga Park, California, United States, 91303
      • Canoga Park
    • Encinitas, California, United States, 92024
      • Encinitas
    • Gardena, California, United States, 90247
      • Gardena
    • Lancaster, California, United States, 93534
      • Lancaster
    • Long Beach, California, United States, 90806
      • Long Beach
    • Long Beach, California, United States, 90805
      • Long Beach
    • Palo Alto, California, United States, 94304
      • Palo Alto
    • Sacramento, California, United States, 95817
      • Sacramento
    • San Diego, California, United States, 92111
      • San Diego
    • San Fernando, California, United States, 91340
      • San Fernando
    • Valley Village, California, United States, 91607
      • Valley Village
    • West Covina, California, United States, 91790
      • West Covina
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Aurora
    • Greenwood Village, Colorado, United States, 80111
      • Greenwood Village
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20011
      • Washington
    • Washington D.C., District of Columbia, United States, 20036
      • Washington
  • Florida
    • Aventura, Florida, United States, 33180
      • Aventura
    • Boynton Beach, Florida, United States, 33435
      • Boynton Beach
    • Davie, Florida, United States, 33024
      • Davie
    • DeLand, Florida, United States, 32720
      • Deland
    • Hialeah, Florida, United States, 33016
      • Hialeah
    • Jacksonville, Florida, United States, 32256
      • Jacksonville
    • Kissimmee, Florida, United States, 34741
      • Kissimmee
    • Lake Worth, Florida, United States, 33461
      • Lake Worth
    • Loxahatchee Groves, Florida, United States, 33470
      • Loxahatchee
    • Margate, Florida, United States, 33063
      • Margate
    • Miami, Florida, United States, 33126
      • Miami
    • Miami, Florida, United States, 33155
      • Miami
    • Miami, Florida, United States, 33140
      • Miami
    • Miami, Florida, United States, 33173
      • Miami
    • New Port Richey, Florida, United States, 34652
      • New Port Richey
    • Orlando, Florida, United States, 32808
      • Orlando
    • Orlando, Florida, United States, 32822
      • Orlando
    • Panama City, Florida, United States, 32405
      • Panama City
    • Sarasota, Florida, United States, 34239
      • Sarasota
  • Georgia
    • Atlanta, Georgia, United States, 30363
      • Atlanta
    • Atlanta, Georgia, United States, 30328
      • Atlanta
    • College Park, Georgia, United States, 30349
      • College Park
    • Columbus, Georgia, United States, 31909
      • Columbus
    • Norcross, Georgia, United States, 30093
      • Norcross
    • Sandy Springs, Georgia, United States, 30328
      • Sandy Springs
    • Savannah, Georgia, United States, 31406
      • Savannah
    • Smyrna, Georgia, United States, 30082
      • Smyrna
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Meridian
    • Nampa, Idaho, United States, 83687
      • Nampa
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Chicago
    • Chicago, Illinois, United States, 60607
      • Chicago
  • Indiana
    • Brownsburg, Indiana, United States, 46112
      • Brownsburg
    • Mishawaka, Indiana, United States, 46545
      • Mishawaka
  • Kansas
    • Shawnee, Kansas, United States, 66218
      • Shawnee
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Covington
    • Marrero, Louisiana, United States, 70072
      • Marrero
    • Metairie, Louisiana, United States, 70001
      • Metairie
    • New Orleans, Louisiana, United States, 70127
      • New Orleans
    • Shreveport, Louisiana, United States, 71118
      • Shreveport
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Baltimore
    • Towson, Maryland, United States, 21204
      • Towson
  • Michigan
    • Dearborn Heights, Michigan, United States, 48127
      • Dearborn Heights
    • Detroit, Michigan, United States, 48201
      • Detroit
    • Saginaw, Michigan, United States, 48602
      • Saginaw
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Jackson
  • Missouri
    • St Louis, Missouri, United States, 63108
      • Saint Louis
    • St Louis, Missouri, United States, 63141
      • Saint Louis
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Las Vegas
    • Las Vegas, Nevada, United States, 89109
      • Las Vegas
    • North Las Vegas, Nevada, United States, 89030
      • North Las Vegas
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08034
      • Cherry Hill
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque
  • New York
    • New York, New York, United States, 10029
      • New York
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Durham
    • New Bern, North Carolina, United States, 28562
      • New Bern
    • Raleigh, North Carolina, United States, 27612
      • Raleigh
    • Raleigh, North Carolina, United States, 27607
      • Raleigh
    • Winston-Salem, North Carolina, United States, 27103
      • Winston-Salem
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Minot
  • Ohio
    • Columbus, Ohio, United States, 43231
      • Columbus
    • Columbus, Ohio, United States, 43210
      • Columbus
    • Columbus, Ohio, United States, 43213
      • Columbus
    • Fairfield, Ohio, United States, 45014
      • Fairfield
    • Franklin, Ohio, United States, 45005
      • Franklin
  • Oregon
    • Portland, Oregon, United States, 97239
      • Portland
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia
    • Philadelphia, Pennsylvania, United States, 19114
      • Philadelphia
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Myrtle Beach
    • Summerville, South Carolina, United States, 29485
      • Summerville
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga
    • Memphis, Tennessee, United States, 38120
      • Memphis
  • Texas
    • Austin, Texas, United States, 78705
      • Austin
    • Beaumont, Texas, United States, 77702
      • Beaumont
    • Dallas, Texas, United States, 75230
      • Dallas
    • Fort Worth, Texas, United States, 76104
      • Fort Worth
    • Houston, Texas, United States, 77054
      • Houston
    • Houston, Texas, United States, 77021
      • Houston
    • Houston, Texas, United States, 77024
      • Houston
    • League City, Texas, United States, 77573
      • League City
    • Pearland, Texas, United States, 77584
      • Pearland
    • San Antonio, Texas, United States, 78233
      • San Antonio
    • San Antonio, Texas, United States, 78258
      • San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Salt Lake City
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Annandale
    • Norfolk, Virginia, United States, 23502
      • Norfolk
  • Washington
    • Bellevue, Washington, United States, 98007
      • Bellevue
    • Seattle, Washington, United States, 98105
      • Seattle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relugolix/E2/NETA; Participants will receive relugolix combination therapy for 1 year (13 consecutive 28-day treatment cycles).	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 Names: Myfembree

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the At-Risk Pearl Index (PI)	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.	13 consecutive 28-day treatment cycles

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Modified At-Risk PI	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.	13 consecutive 28-day treatment cycles
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Gross PI	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.	13 consecutive 28-day treatment cycles
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Method Failure PI	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.	13 consecutive 28-day treatment cycles
Contraceptive Efficacy of Relugolix Combination Therapy as Assessed by the Cumulative 1-Year Pregnancy Rates	Cumulative 1-year pregnancy rate and the associated 95% CI will be estimated on each of the efficacy analysis populations by the Kaplan-Meier (KM) survival analysis.	13 consecutive 28-day treatment cycles
Number of Participants Who Do Not Complete 13 Treatment Cycles	Proportion of enrolled participants who do not complete 13 treatment cycles. Treatment cycle is defined as consecutive 28-day period	13 consecutive 28-day treatment cycles
Percent Change in Bone Mineral Density From Baseline to 6 and 12 Months On-Treatment	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.	Up to 12 months

Collaborators and Investigators

• Sponsor: Sumitomo Pharma Switzerland GmbH

Publications and helpful links

General Publications

• Neblett MF 2nd, Stewart EA. Oral Gonadotropin-Releasing Hormone Antagonists for the Treatment of Uterine Leiomyomas. Obstet Gynecol. 2023 May 1;141(5):901-910. doi: 10.1097/AOG.0000000000005145. Epub 2023 Apr 5.

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2021
• Primary Completion (Actual): February 25, 2025
• Study Completion (Actual): March 31, 2026

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 12, 2021
• First Posted (Actual): February 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Endometriosis; Uterine Fibroids; Estradiol; Relugolix; Norethindrone acetate
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Genital Diseases, Female; Neoplasms, Connective and Soft Tissue; Neoplasms, Muscle Tissue; Endometriosis; Leiomyoma; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Androgen Antagonists; Relugolix
• Other Study ID Numbers: MVT-601-050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No