A Phase 3B Study to Evaluate Bone Mineral Density With Long-Term Use of Relugolix Combination Tablet in Women With Uterine Fibroids or Endometriosis

Endometriosis Clinical Trial

Official title:

A Phase 3B, Single-Arm, Open-Label Study to Evaluate Bone Mineral Density With Long-Term Use of Relugolix Combination Tablet in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids or Moderate to Severe Pain Associated With Endometriosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05862272
• Other study ID #: MVT-601A-006
• Status: Recruiting
• Phase: Phase 3
• Start date: August 14, 2023
• Est. completion date: September 2030

Study information

• Verified date: March 2024
• Source: Sumitomo Pharma Switzerland GmbH
• Contact: Clinical Trials at Myovant
• Phone: 650-278-8743
• Email: ClinicalTrials[@]Myovant.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical trial to characterize changes in bone mineral density during continuous treatment with relugolix combination tablet for up to 48 months (4 years) and 1 year of post-treatment follow-up in premenopausal women with heavy menstrual bleeding associated with uterine leiomyomas (fibroids) or with moderate-to-severe pain associated with endometriosis.

Description:

A prospective, single-arm, open-label, Phase 3B study to assess the effect of continuous 48 months (4 years) of treatment with relugolix combination tablet (relugolix 40 mg/estradiol [E2] 1 mg/norethindrone acetate [NETA] 0.5 mg) on bone mineral density in premenopausal women with heavy menstrual bleeding associated with uterine leiomyomas (fibroids) and premenopausal women with moderate to severe pain associated with endometriosis. Approximately 1000 women (500 with heavy menstrual bleeding associated with uterine fibroids and 500 with moderate to severe pain associated with endometriosis) will receive relugolix combination tablet, during which time BMD will be assessed by dual-energy X-ray absorptiometry every 6 months. A subset of participants will be eligible to enter this study following completion of 1 year of treatment with relugolix combination therapy in MVT-601-050 (NCT04756037; SERENE) and will complete 3 years of treatment under this protocol. Upon completion of 48 months (4 years) of treatment or after early termination of treatment, participants will enter a 1-year post-treatment follow-up period during which time bone mineral density will be assessed at Month 6 and Month 12 following treatment cessation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: September 2030
• Est. primary completion date: July 2029
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Key Inclusion Criteria:

• Is a premenopausal woman, 18 to 50 years of age (inclusive);
• A diagnosis of uterine fibroids confirmed by imaging or review of medical records and reports heavy menstrual bleeding negatively affecting quality of life. or
• A diagnosis of endometriosis that is associated with moderate to severe pain.;
• If at risk of pregnancy is willing to avoid pregnancy for 4 years (the duration of the treatment period) using nonhormonal methods of contraception.
• Has a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at the allocation visit (or Month 12 if entering from MVT-601-050 [NCT04756037; SERENE]);
• In good physical and mental health based on medical, surgical, and gynecological history as well as physical, gynecological, and breast examinations, clinical laboratory test results, and vital sign measurements;
• Has a body mass index = 18 kg/m^2.

Key Exclusion Criteria:

• Has a weight or body habitus that exceeds the limit of the DXA scanner or has a condition that precludes an adequate DXA measurement at the lumbar spine or proximal femur
• Has a DXA result demonstrating the following criteria at any anatomic site (lumbar

spine, total hip, femoral neck):

1. For patients entering de novo a Z-score = -1.5 or T-score = -2.0 (if = 40 years of age)

2. For patients entering from MVT-601-050 (NCT04756037; SERENE) a 12-month on-treatment DXA demonstrating Z-score = -2.0, T-score = -2.5 (if = 40 years of age), or BMD loss = 8% compared with pre-treatment baseline;

• Screening 25-OH vitamin D level < 12 ng/mL (patients with 25-OH vitamin D deficiency with levels = 12 to < 20 ng/mL are permitted if supplementing with vitamin D or if vitamin D supplementation is started in the screening period);
• Has a history of or currently has Cushing's Syndrome, Rheumatoid Arthritis, metabolic bone disease, uncorrected hyperparathyroidism, Paget's disease of the bone, collagen vascular disease, Marfan's syndrome, Ehlers-Danlos syndrome (if confirmed on genetic testing or meets definitive criteria for hypermobility type), 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, hyperprolactinemia, known pituitary adenoma, hyperthyroidism, anorexia nervosa, bulimia (within the last year), abnormal bone mineral metabolism (eg, hypophosphatemia). Patients whose hyperparathyroidism or hyperthyroidism has been successfully treated or whose hyperprolactinemia has been successfully treated are allowed;
• History of low trauma (fragility) fracture.
• Past history of use or current use of medication used to treat bone loss other than calcium and vitamin D preparations;
• Prior use of depot-medroxyprogesterone acetate for a treatment period > 2 years (if treatment occurred within the past 5 years) or prior use of GnRH agonist or antagonist for > 12 months total (unless directly entering from MVT-601-050 [NCT04756037; SERENE]);
• Malabsorptive disease (including, but not limited to, inflammatory bowel disease and gastric bypass surgery);
• Current breast cancer, history of breast cancer or other hormone-sensitive malignancy, at increased risk for hormone-sensitive malignancy, or taking an aromatase inhibitor for breast cancer treatment or prevention
• History of organ transplantation or history of bone marrow
• BIRADS = 3 Mammogram at entry (or within the past 6 months).
• Has a known human immunodeficiency virus (HIV) infection or at high risk of contracting HIV
• Has a current psychiatric disorder that would, in the investigator or medical monitor's opinion, impair the ability of the patient to participate in the study or would impair interpretation of their data.
• Is currently using a hormonal intrauterine device or contraceptive implant, hormonal contraceptive, or other prohibited medication and is unwilling to discontinue this hormonal contraception

Related Conditions & MeSH terms

• Endometriosis
• Leiomyoma
• Uterine Fibroids

Intervention

Drug:
• Relugolix Combination Tablet
A fixed-dose combination tablet containing relugolix 40 mg, estradiol (E2) 1 mg, and norethindrone acetate (NETA) 0.5 mg.

Locations

Country	Name	City	State
United States	Arlington	Arlington	Texas
United States	Atlanta	Atlanta	Georgia
United States	Atlanta	Atlanta	Georgia
United States	Aventura	Aventura	Florida
United States	Bay City	Bay City	Michigan
United States	Canoga Park	Canoga Park	California
United States	Chandler	Chandler	Arizona
United States	Chattanooga	Chattanooga	Tennessee
United States	Chicago	Chicago	Illinois
United States	Cincinnati	Cincinnati	Ohio
United States	College Park	College Park	Georgia
United States	Columbus	Columbus	Ohio
United States	Columbus	Columbus	Ohio
United States	Dallas	Dallas	Texas
United States	Dearborn Heights	Dearborn Heights	Michigan
United States	Deland	DeLand	Florida
United States	Draper	Draper	Utah
United States	Dublin	Dublin	Ohio
United States	Durham	Durham	North Carolina
United States	Encinitas	Encinitas	California
United States	Englewood	Englewood	Ohio
United States	Erie	Erie	Pennsylvania
United States	Grand Island	Grand Island	Nebraska
United States	Greenwood Village	Greenwood Village	Colorado
United States	Hialeah	Hialeah	Florida
United States	Houston	Houston	Texas
United States	Houston	Houston	Texas
United States	Houston	Houston	Texas
United States	Idaho Falls	Idaho Falls	Idaho
United States	Inglewood	Inglewood	California
United States	Jackson	Jackson	Tennessee
United States	Jackson	Jackson	Mississippi
United States	Kissimmee	Kissimmee	Florida
United States	Lake Worth	Lake Worth	Florida
United States	Lakewood	Lakewood	Colorado
United States	Las Vegas	Las Vegas	Nevada
United States	League City	League City	Texas
United States	Long Beach	Long Beach	California
United States	Los Angeles	Los Angeles	California
United States	Margate	Margate	Florida
United States	Marrero	Marrero	Louisiana
United States	Memphis	Memphis	Tennessee
United States	Memphis	Memphis	Tennessee
United States	Meridian	Meridian	Idaho
United States	Mesa	Mesa	Arizona
United States	Metairie	Metairie	Louisiana
United States	Miami	Miami	Florida
United States	Miami	Miami	Florida
United States	Miami	Miami	Florida
United States	Miami Springs	Miami Springs	Florida
United States	Mobile	Mobile	Alabama
United States	New Bern	New Bern	North Carolina
United States	New Orleans	New Orleans	Louisiana
United States	New Port Richey	New Port Richey	Florida
United States	Newport News	Newport News	Virginia
United States	Norcross	Norcross	Georgia
United States	Norfolk	Norfolk	Nebraska
United States	Norfolk	Norfolk	Virginia
United States	North Las Vegas	North Las Vegas	Nevada
United States	Orlando	Orlando	Florida
United States	Palo Alto	Palo Alto	California
United States	Panama City	Panama City	Florida
United States	Passaic	Passaic	New Jersey
United States	Pearland	Pearland	Texas
United States	Philadelphia	Philadelphia	Pennsylvania
United States	Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix	Phoenix	Arizona
United States	Raleigh	Raleigh	North Carolina
United States	Raleigh	Raleigh	North Carolina
United States	Reston	Reston	Virginia
United States	St Louis	Saint Louis	Missouri
United States	Salt Lake City	Salt Lake City	Utah
United States	San Antonio	San Antonio	Texas
United States	Sarasota	Sarasota	Florida
United States	Savannah	Savannah	Georgia
United States	Seattle	Seattle	Washington
United States	Shawnee	Shawnee Mission	Kansas
United States	Slidell	Slidell	Louisiana
United States	Smyrna	Smyrna	Georgia
United States	Sugar Land	Sugar Land	Texas
United States	Tamarac	Tamarac	Florida
United States	Tampa	Tampa	Florida
United States	Towson	Towson	Maryland
United States	Tucson	Tucson	Arizona
United States	Valley Village	Valley Village	California
United States	Venice	Venice	Florida
United States	Washington	Washington	District of Columbia
United States	Webster	Webster	Texas
United States	West Columbia	West Columbia	South Carolina
United States	West Palm Beach	West Palm Beach	Florida
United States	Wichita	Wichita	Kansas
United States	Winston Salem	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma Switzerland GmbH

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change from baseline in BMD (bone mineral density) at Month 48 on-treatment at lumbar spine (L1-L4) in women with uterine fibroids.	Assessed by dual-energy X-ray absorptiometry (DXA) scan.	Baseline up to Month 48
Primary	Percent change from baseline in BMD at Month 48 on-treatment at lumbar spine (L1-L4) in women with endometriosis.	Assessed by dual-energy X-ray absorptiometry (DXA) scan.	Baseline up to Month 48
Secondary	Percent change from baseline in BMD at Month 48 on-treatment at total hip and femoral neck in women with uterine fibroids.	Assessed by dual-energy X-ray absorptiometry (DXA) scan.	Baseline up to Month 48
Secondary	Percent change from baseline in BMD at Month 48 on-treatment at total hip and femoral neck in women with endometriosis.	Assessed by dual-energy X-ray absorptiometry (DXA) scan.	Baseline up to Month 48
Secondary	Percent change from baseline in BMD at Month 6, 12, 18, 24, 30, 36, and 42 on-treatment at the lumbar spine (L1-L4), total hip, and femoral neck in women with uterine fibroids.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	Baseline up to Month 6, 12, 18, 24, 30, 36, and 42
Secondary	Percent change from baseline in BMD at Month 6, 12, 18, 24, 30, 36, and 42 on-treatment at the lumbar spine (L1-L4), total hip, and femoral neck in women with endometriosis.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	Baseline up to Month 6, 12, 18, 24, 30, 36, and 42
Secondary	Percent change from baseline in BMD at Month 48 on-treatment at lumbar spine (L1-L4) in the overall study population.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	Baseline up to Month 48
Secondary	Percent change from baseline in BMD at Month 48 on-treatment at total hip and femoral neck in the overall study population.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	Baseline up to Month 48
Secondary	Percent change from baseline in BMD at Month 6, 12, 18, 24, 30, 36, and 42 on-treatment at the lumbar spine (L1-L4), total hip, and femoral neck in the overall study population.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	Baseline up to Month 6, 12, 18, 24, 30, 36, and 42
Secondary	Percent change from baseline in BMD at post-treatment follow-up (PTFU) Month 6 and PTFU Month 12 at the lumbar spine (L1-L4), total hip, and femoral neck in women with uterine fibroids.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	6 months and 12 months post treatment
Secondary	Percent change from baseline in BMD at PTFU Month 6 and PTFU Month 12 at the lumbar spine (L1-L4), total hip, and femoral neck in women with endometriosis.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	6 months and 12 months post treatment
Secondary	Percent change from last on-treatment BMD measurement to PTFU Month 6 and PTFU Month 12 at the lumbar spine (L1-L4), total hip, and femoral neck in women with uterine fibroids.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	6 months and 12 months post treatment
Secondary	Percent change from last on-treatment BMD measurement to PTFU Month 6 and PTFU Month 12 at the lumbar spine (L1-L4), total hip, and femoral neck in women with endometriosis.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	6 months and 12 months post treatment
Secondary	Percent change from baseline in BMD at PTFU Month 6 and PTFU Month 12 at the lumbar spine (L1-L4), total hip, and femoral neck in the overall study population.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	6 months and 12 months post treatment
Secondary	Percent change from last on-treatment BMD measurement to PTFU Month 6 and PTFU Month 12 at the lumbar spine (L1-L4), total hip, and femoral neck in the overall study population.	Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.	6 months and 12 months post treatment
Secondary	Incidence of treatment-emergent serious adverse events, and non-serious adverse events leading to treatment discontinuation or withdrawal from the study during the 48 months of treatment.	Safety analyses will be conducted by each safety population: 1) women with uterine fibroids, 2) women with endometriosis, and 3) overall population. The treatment-emergent period will be defined as the period of time from the date of the first dose of the study drug through 14 days after the last dose of study drug, or the date of initiation of another investigational agent or hormonal therapy affecting the hypothalamic-pituitary gonadal axis or surgical intervention for uterine fibroids or for endometriosis, whichever occurs first.	Baseline up to Month 48
Secondary	Incidence and location of fractures during the 48 months on treatment and 12 months PTFU.	Safety analyses will be conducted by each safety population: 1) women with uterine fibroids, 2) women with endometriosis, and 3) overall population. All adverse events will be coded to preferred term and system organ class using Medical Dictionary for Regulatory Activities (MedDRA) version 24.0 or higher. The incidence of fractures will also be summarized by anatomical sites and whether the fracture qualifies as a fragility fracture. A participant reporting the same adverse event more than once is counted once, and at the maximum severity or strongest relationship to study drug treatment when calculating incidence.	Baseline up to Month 48 and 12 months post treatment