Clinical trial NCT05862272: A Phase 3B Study to Evaluate Bone Mineral Density with Long-Term Use of Relugolix Combination Tablet in Women with Uterine Fibroids or Endometriosis
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Uterine Fibroids
Endometriosis
Keywords: Uterine Leiomyomas
Fibroids
Endometriosis
Bone Mineral Density
Relugolix
Estradiol
Norethindrone acetate
Lead sponsor: Sumitomo Pharma Switzerland GmbH
Sponsor class: INDUSTRY
First posted: 2023-05-17
Enrollment: 1000
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent change from baseline in BMD (bone mineral density) at Month 48 on-treatment at lumbar spine (L1-L4) in women with uterine fibroids.
timeFrame: Baseline up to Month 48
measure: Percent change from baseline in BMD at Month 48 on-treatment at lumbar spine (L1-L4) in women with endometriosis.
timeFrame: Baseline up to Month 48
Secondary outcomes:
measure: Percent change from baseline in BMD at Month 48 on-treatment at total hip and femoral neck in women with uterine fibroids.
timeFrame: Baseline up to Month 48
measure: Percent change from baseline in BMD at Month 48 on-treatment at total hip and femoral neck in women with endometriosis.
timeFrame: Baseline up to Month 48
measure: 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.
timeFrame: Baseline up to Month 6, 12, 18, 24, 30, 36, and 42
measure: 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.
timeFrame: Baseline up to Month 6, 12, 18, 24, 30, 36, and 42
measure: Percent change from baseline in BMD at Month 48 on-treatment at lumbar spine (L1-L4) in the overall study population.
timeFrame: Baseline up to Month 48
measure: Percent change from baseline in BMD at Month 48 on-treatment at total hip and femoral neck in the overall study population.
timeFrame: Baseline up to Month 48
measure: 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.
timeFrame: Baseline up to Month 6, 12, 18, 24, 30, 36, and 42
measure: 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.
timeFrame: 6 months and 12 months post treatment
measure: 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.
timeFrame: 6 months and 12 months post treatment
measure: 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.
timeFrame: 6 months and 12 months post treatment
measure: 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.
timeFrame: 6 months and 12 months post treatment
measure: 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.
timeFrame: 6 months and 12 months post treatment
measure: 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.
timeFrame: 6 months and 12 months post treatment
measure: 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.
timeFrame: Baseline up to Month 48
measure: Incidence and location of fractures during the 48 months on treatment and 12 months PTFU.
timeFrame: Baseline up to Month 48 and 12 months post treatment
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile
state: Alabama
city: Chandler
country: United States
facility: Chandler
state: Arizona
city: Mesa
country: United States
facility: Mesa
state: Arizona
city: Phoenix
country: United States
facility: Phoenix
state: Arizona
city: Tucson
country: United States
facility: Tucson
state: Arizona
city: Canoga Park
country: United States
facility: Canoga Park
state: California
city: Encinitas
country: United States
facility: Encinitas
state: California
city: Inglewood
country: United States
facility: Inglewood
state: California
city: Long Beach
country: United States
facility: Long Beach
state: California
city: Los Angeles
country: United States
facility: Los Angeles
state: California
city: Palo Alto
country: United States
facility: Palo Alto
state: California
city: Valley Village
country: United States
facility: Valley Village
state: California
city: Greenwood Village
country: United States
facility: Greenwood Village
state: Colorado
city: Lakewood
country: United States
facility: Lakewood
state: Colorado
city: Washington
country: United States
facility: Washington
state: District of Columbia
city: Aventura
country: United States
facility: Aventura
state: Florida
city: Deland
country: United States
facility: Deland
state: Florida
city: Hialeah
country: United States
facility: Hialeah
state: Florida
city: Kissimmee
country: United States
facility: Kissimmee
state: Florida
city: Lake Worth
country: United States
facility: Lake Worth
state: Florida
city: Margate
country: United States
facility: Margate
state: Florida
city: Miami Springs
country: United States
facility: Miami Springs
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: Miami
country: United States
facility: Miami
state: Florida
city: New Port Richey
country: United States
facility: New Port Richey
state: Florida
city: Orlando
country: United States
facility: Orlando
state: Florida
city: Panama City
country: United States
facility: Panama City
state: Florida
city: Sarasota
country: United States
facility: Sarasota
state: Florida
city: Tamarac
country: United States
facility: Tamarac
state: Florida
city: Tampa
country: United States
facility: Tampa
state: Florida
city: Venice
country: United States
facility: Venice
state: Florida
city: West Palm Beach
country: United States
facility: West Palm Beach
state: Florida
city: Atlanta
country: United States
facility: Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Atlanta
state: Georgia
city: College Park
country: United States
facility: College Park
state: Georgia
city: Norcross
country: United States
facility: Norcross
state: Georgia
city: Savannah
country: United States
facility: Savannah
state: Georgia
city: Smyrna
country: United States
facility: Smyrna
state: Georgia
city: Idaho Falls
country: United States
facility: Idaho Falls
state: Idaho
city: Meridian
country: United States
facility: Meridian
state: Idaho
city: Chicago
country: United States
facility: Chicago
state: Illinois
city: Shawnee
country: United States
facility: Shawnee
state: Kansas
city: Wichita
country: United States
facility: Wichita
state: Kansas
city: Marrero
country: United States
facility: Marrero
state: Louisiana
city: Metairie
country: United States
facility: Metairie
state: Louisiana
city: New Orleans
country: United States
facility: New Orleans
state: Louisiana
city: Slidell
country: United States
facility: Slidell
state: Louisiana
city: Towson
country: United States
facility: Towson
state: Maryland
city: Bay City
country: United States
facility: Bay City
state: Michigan
city: Dearborn Heights
country: United States
facility: Dearborn Heights
state: Michigan
city: Jackson
country: United States
facility: Jackson
state: Mississippi
city: St Louis
country: United States
facility: St Louis
state: Missouri
city: Grand Island
country: United States
facility: Grand Island
state: Nebraska
city: Norfolk
country: United States
facility: Norfolk
state: Nebraska
city: Las Vegas
country: United States
facility: Las Vegas
state: Nevada
city: North Las Vegas
country: United States
facility: North Las Vegas
state: Nevada
city: Passaic
country: United States
facility: Passaic
state: New Jersey
city: Durham
country: United States
facility: Durham
state: North Carolina
city: New Bern
country: United States
facility: New Bern
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh
state: North Carolina
city: Winston Salem
country: United States
facility: Winston Salem
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland
state: Ohio
city: Columbus
country: United States
facility: Columbus
state: Ohio
city: Columbus
country: United States
facility: Columbus
state: Ohio
city: Dublin
country: United States
facility: Dublin
state: Ohio
city: Englewood
country: United States
facility: Englewood
state: Ohio
city: Erie
country: United States
facility: Erie
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia
state: Pennsylvania
city: West Columbia
country: United States
facility: West Columbia
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga
state: Tennessee
city: Jackson
country: United States
facility: Jackson
state: Tennessee
city: Memphis
country: United States
facility: Memphis
state: Tennessee
city: Memphis
country: United States
facility: Memphis
state: Tennessee
city: Arlington
country: United States
facility: Arlington
state: Texas
city: Dallas
country: United States
facility: Dallas
state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: Houston
country: United States
facility: Houston
state: Texas
city: League City
country: United States
facility: League City
state: Texas
city: Pearland
country: United States
facility: Pearland
state: Texas
city: San Antonio
country: United States
facility: San Antonio
state: Texas
city: Sugar Land
country: United States
facility: Sugar Land
state: Texas
city: Webster
country: United States
facility: Webster
state: Texas
city: Draper
country: United States
facility: Draper
state: Utah
city: Salt Lake City
country: United States
facility: Salt Lake City
state: Utah
city: Newport News
country: United States
facility: Newport News
state: Virginia
city: Norfolk
country: United States
facility: Norfolk
state: Virginia
city: Reston
country: United States
facility: Reston
state: Virginia
city: Seattle
country: United States
facility: Seattle
state: Washington
Study officials:
affiliation: Myovant Sciences GmbH
name: Myovant Medical Director
role: STUDY_DIRECTOR
References: