A Phase 3B Study to Evaluate Bone Mineral Density With Long-Term Use of Relugolix Combination Tablet in Women With Uterine Fibroids or Endometriosis
- Conditions
- Uterine FibroidsEndometriosis
- Interventions
- Registration Number
- NCT05862272
- Lead Sponsor
- Sumitomo Pharma Switzerland GmbH
- Brief 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.
- Detailed 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 & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 1000
- 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
-
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):
- For patients entering de novo a Z-score ≤ -1.5 or T-score ≤ -2.0 (if ≥ 40 years of age)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Relugolix Combination Tablet Relugolix Combination Tablet Participants will receive relugolix combination therapy orally once daily for 48 months.
- Primary Outcome Measures
Name Time Method Percent change from baseline in BMD (bone mineral density) at Month 48 on-treatment at lumbar spine (L1-L4) in women with uterine fibroids. Baseline up to Month 48 Assessed by dual-energy X-ray absorptiometry (DXA) scan.
Percent change from baseline in BMD at Month 48 on-treatment at lumbar spine (L1-L4) in women with endometriosis. Baseline up to Month 48 Assessed by dual-energy X-ray absorptiometry (DXA) scan.
- Secondary Outcome Measures
Name Time Method Percent change from baseline in BMD at Month 48 on-treatment at total hip and femoral neck in women with endometriosis. Baseline up to Month 48 Assessed by dual-energy X-ray absorptiometry (DXA) scan.
Percent change from baseline in BMD at Month 48 on-treatment at total hip and femoral neck in the overall study population. Baseline up to Month 48 Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
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. 6 months and 12 months post treatment Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
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. Baseline up to Month 48 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.
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. 6 months and 12 months post treatment Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
Percent change from baseline in BMD at Month 48 on-treatment at total hip and femoral neck in women with uterine fibroids. Baseline up to Month 48 Assessed by dual-energy X-ray absorptiometry (DXA) scan.
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. Baseline up to Month 6, 12, 18, 24, 30, 36, and 42 Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
Incidence and location of fractures during the 48 months on treatment and 12 months PTFU. Baseline up to Month 48 and 12 months post treatment 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.
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. Baseline up to Month 6, 12, 18, 24, 30, 36, and 42 Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
Percent change from baseline in BMD at Month 48 on-treatment at lumbar spine (L1-L4) in the overall study population. Baseline up to Month 48 Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
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. Baseline up to Month 6, 12, 18, 24, 30, 36, and 42 Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
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. 6 months and 12 months post treatment Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
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. 6 months and 12 months post treatment Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
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. 6 months and 12 months post treatment Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
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. 6 months and 12 months post treatment Assessed by dual-energy X-ray absorptiometry (DXA) scan at each designated time points.
Trial Locations
- Locations (82)
Mesa
🇺🇸Mesa, Arizona, United States
Erie
🇺🇸Erie, Pennsylvania, United States
Meridian
🇺🇸Meridian, Idaho, United States
Cleveland
🇺🇸Cleveland, Ohio, United States
Mobile
🇺🇸Mobile, Alabama, United States
Chandler
🇺🇸Chandler, Arizona, United States
Phoenix
🇺🇸Phoenix, Arizona, United States
Tucson
🇺🇸Tucson, Arizona, United States
Canoga Park
🇺🇸Canoga Park, California, United States
Encinitas
🇺🇸Encinitas, California, United States
Inglewood
🇺🇸Inglewood, California, United States
Long Beach
🇺🇸Long Beach, California, United States
Los Angeles
🇺🇸Los Angeles, California, United States
Palo Alto
🇺🇸Palo Alto, California, United States
Valley Village
🇺🇸Valley Village, California, United States
Greenwood Village
🇺🇸Greenwood Village, Colorado, United States
Lakewood
🇺🇸Lakewood, Colorado, United States
Washington
🇺🇸Washington, District of Columbia, United States
Aventura
🇺🇸Aventura, Florida, United States
Deland
🇺🇸Deland, Florida, United States
Hialeah
🇺🇸Hialeah, Florida, United States
Kissimmee
🇺🇸Kissimmee, Florida, United States
Lake Worth
🇺🇸Lake Worth, Florida, United States
Margate
🇺🇸Margate, Florida, United States
Miami Springs
🇺🇸Miami Springs, Florida, United States
Miami
🇺🇸Miami, Florida, United States
New Port Richey
🇺🇸New Port Richey, Florida, United States
Orlando
🇺🇸Orlando, Florida, United States
Panama City
🇺🇸Panama City, Florida, United States
Sarasota
🇺🇸Sarasota, Florida, United States
Tamarac
🇺🇸Tamarac, Florida, United States
Tampa
🇺🇸Tampa, Florida, United States
Venice
🇺🇸Venice, Florida, United States
West Palm Beach
🇺🇸West Palm Beach, Florida, United States
Atlanta
🇺🇸Atlanta, Georgia, United States
College Park
🇺🇸College Park, Georgia, United States
Norcross
🇺🇸Norcross, Georgia, United States
Savannah
🇺🇸Savannah, Georgia, United States
Smyrna
🇺🇸Smyrna, Georgia, United States
Idaho Falls
🇺🇸Idaho Falls, Idaho, United States
Chicago
🇺🇸Chicago, Illinois, United States
Shawnee
🇺🇸Shawnee, Kansas, United States
Wichita
🇺🇸Wichita, Kansas, United States
Marrero
🇺🇸Marrero, Louisiana, United States
Metairie
🇺🇸Metairie, Louisiana, United States
New Orleans
🇺🇸New Orleans, Louisiana, United States
Slidell
🇺🇸Slidell, Louisiana, United States
Towson
🇺🇸Towson, Maryland, United States
Bay City
🇺🇸Bay City, Michigan, United States
Dearborn Heights
🇺🇸Dearborn Heights, Michigan, United States
Jackson
🇺🇸Jackson, Tennessee, United States
St Louis
🇺🇸St Louis, Missouri, United States
Grand Island
🇺🇸Grand Island, Nebraska, United States
Norfolk
🇺🇸Norfolk, Virginia, United States
Las Vegas
🇺🇸Las Vegas, Nevada, United States
North Las Vegas
🇺🇸North Las Vegas, Nevada, United States
Passaic
🇺🇸Passaic, New Jersey, United States
Durham
🇺🇸Durham, North Carolina, United States
New Bern
🇺🇸New Bern, North Carolina, United States
Raleigh
🇺🇸Raleigh, North Carolina, United States
Winston Salem
🇺🇸Winston Salem, North Carolina, United States
Cincinnati
🇺🇸Cincinnati, Ohio, United States
Columbus
🇺🇸Columbus, Ohio, United States
Dublin
🇺🇸Dublin, Ohio, United States
Englewood
🇺🇸Englewood, Ohio, United States
Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
West Columbia
🇺🇸West Columbia, South Carolina, United States
Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Memphis
🇺🇸Memphis, Tennessee, United States
Arlington
🇺🇸Arlington, Texas, United States
Dallas
🇺🇸Dallas, Texas, United States
Houston
🇺🇸Houston, Texas, United States
League City
🇺🇸League City, Texas, United States
Pearland
🇺🇸Pearland, Texas, United States
San Antonio
🇺🇸San Antonio, Texas, United States
Sugar Land
🇺🇸Sugar Land, Texas, United States
Webster
🇺🇸Webster, Texas, United States
Draper
🇺🇸Draper, Utah, United States
Salt Lake City
🇺🇸Salt Lake City, Utah, United States
Newport News
🇺🇸Newport News, Virginia, United States
Reston
🇺🇸Reston, Virginia, United States
Seattle
🇺🇸Seattle, Washington, United States