Relugolix for Uterine Fibroids

Recruiting at 85 trial locations

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Myovant Sciences GmbH

Must be taking: Vitamin D

Must not be taking: Hormonal contraceptives

Disqualifiers: Cushing's, Rheumatoid arthritis, CKD, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to stop using hormonal contraceptives or other prohibited medications. If you are currently using these, you will need to discontinue them to join the study.

What data supports the effectiveness of the drug Relugolix Combination Tablet for treating uterine fibroids?

Research shows that the Relugolix Combination Tablet significantly reduces heavy menstrual bleeding and other symptoms associated with uterine fibroids. In clinical trials, it was well tolerated and helped maintain bone health over long-term use. ^{1 2 3 4 5}

Is Relugolix safe for treating uterine fibroids?

Relugolix combination therapy, used for uterine fibroids, is generally well tolerated with the most common side effects being hot flashes and other vasomotor symptoms (like sweating and flushing). Long-term use did not lead to significant bone loss in most women, making it a safe option for many. ^{1 2 3 4 6}

How is the drug Relugolix Combination Tablet unique for treating uterine fibroids?

Relugolix Combination Tablet is unique because it is the first and only once-daily oral therapy that combines a GnRH receptor antagonist with estradiol and norethindrone acetate to manage heavy menstrual bleeding and other symptoms of uterine fibroids, while also preventing bone loss and hot flashes. ^{1 2 3 4 7}

Research Team

Myovant Medical Director

Principal Investigator

Myovant Sciences GmbH

Eligibility Criteria

This trial is for premenopausal women aged 18-50 with uterine fibroids or endometriosis causing heavy menstrual bleeding or pain. Participants must not be at risk of pregnancy or agree to nonhormonal contraception for 4 years, have a BMI ≥ 18 kg/m^2, and cannot have certain bone density issues, vitamin D deficiencies without supplementation, history of specific cancers, organ transplants, psychiatric disorders affecting study participation, or use prohibited medications.

Inclusion Criteria

If at risk of pregnancy, is willing to avoid pregnancy for 4 years using nonhormonal methods of contraception

I am in good physical and mental health according to recent exams and tests.

Has a body mass index ≥ 18 kg/m^2

Exclusion Criteria

I have or am at risk for hormone-sensitive cancer, or I'm taking medication for it.

I have had an organ or bone marrow transplant.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive relugolix combination therapy orally once daily for 48 months to assess changes in bone mineral density.

48 months

DXA scans every 6 months

Follow-up

Participants are monitored for changes in bone mineral density post-treatment.

12 months

DXA scans at Month 6 and Month 12

Treatment Details

Interventions

• Relugolix Combination Tablet (Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist)

Trial Overview The trial studies the long-term effects (up to 48 months) of Relugolix Combination Tablet on bone mineral density in women with uterine fibroids or endometriosis. It includes continuous treatment and a follow-up year to monitor changes in bone health.

Participant Groups

Group I: Relugolix Combination Tablet Experimental Treatment 1 Intervention

Participants will receive relugolix combination therapy orally once daily for 48 months.

Who Is Running the Clinical Trial?

Myovant Sciences GmbH

Lead Sponsor

Trials

23

Recruited

12,500+

Sumitomo Pharma Switzerland GmbH

Lead Sponsor

Trials

19

Recruited

6,900+

Findings from Research

The combination of relugolix, estradiol, and norethisterone acetate (Ryeqo®; Myfembree®) effectively reduces heavy menstrual bleeding and improves other symptoms associated with uterine fibroids, as demonstrated in two phase 3 LIBERTY trials.

This treatment is generally well tolerated, with minimal risk of clinically significant bone loss over up to 2 years, making it a safe and convenient once-daily option for premenopausal women suffering from symptomatic uterine fibroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids. Syed, YY.[2022]

In a post hoc analysis of the LIBERTY 1 and LIBERTY 2 trials involving 124 European women, relugolix combination therapy (relugolix-CT) significantly reduced uterine fibroid-associated symptoms, with 85.4% of women responding positively compared to only 19.1% in the placebo group.

Relugolix-CT not only improved menstrual blood loss and pain but also preserved bone mineral density, indicating it is a safe and effective treatment option for women suffering from heavy menstrual bleeding due to uterine fibroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix combination therapy in European women with symptomatic uterine fibroids: a subgroup analysis from the randomized phase 3 LIBERTY pivotal trials. Venturella, R., Rechberger, T., Zatik, J., et al.[2023]

In a 2-year study involving 229 women with uterine fibroids, relugolix combination therapy significantly maintained low menstrual blood loss volume (<80 mL) in 78.4% of participants compared to only 15.1% in the placebo group, demonstrating its efficacy in managing symptoms associated with uterine fibroids.

The treatment was well tolerated over the 2 years, with no new safety concerns and stable bone mineral density, indicating that relugolix combination therapy is a safe long-term option for women suffering from heavy menstrual bleeding due to uterine fibroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LIBERTY randomized withdrawal study: relugolix combination therapy for heavy menstrual bleeding associated with uterine fibroids. Al-Hendy, A., Venturella, R., Arjona Ferreira, JC., et al.[2023]

Relugolix is an innovative oral GnRH receptor antagonist that effectively reduces heavy menstrual bleeding and pain associated with uterine fibroids and endometriosis by suppressing estrogen and progesterone production, making it a significant advancement in medical management for these conditions.

The combination therapy of relugolix with estradiol and norethindrone acetate has been approved as MYFEMBREE in the U.S. and RYEQO in the EU, providing a long-term treatment option that mitigates the risk of hypoestrogenic side effects, such as bone density loss, while improving quality of life for women suffering from these disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of relugolix combination therapy as a medical treatment option for women with uterine fibroids or endometriosis. Arjona Ferreira, JC., Migoya, E.[2023]

In a study involving 241 Black or African American women with uterine fibroids, 82.9% achieved significant reductions in heavy menstrual bleeding after 52 weeks of treatment with once-daily relugolix combination therapy, indicating its high efficacy in this population.

The treatment was well-tolerated, with preserved bone mineral density and manageable side effects, such as hot flushes and headaches, suggesting that relugolix combination therapy is a safe option for managing uterine fibroid symptoms in Black or African American women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix combination therapy in Black/African American women with symptomatic uterine fibroids: LIBERTY Long-Term Extension study. Stewart, EA., Al-Hendy, A., Lukes, AS., et al.[2023]

In a Phase 3 study involving 65 premenopausal women, relugolix significantly reduced uterine fibroid-associated pain, with 57.6% of patients achieving a maximum pain score of ≤1 compared to only 3.1% in the placebo group.

While relugolix was associated with a higher incidence of mild to moderate treatment-emergent adverse events (87.9% vs. 56.3% for placebo), the overall safety profile was acceptable, with low rates of treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix, a novel oral gonadotropin-releasing hormone antagonist, in the treatment of pain symptoms associated with uterine fibroids: a randomized, placebo-controlled, phase 3 study in Japanese women. Osuga, Y., Enya, K., Kudou, K., et al.[2020]

Relugolix combination therapy is an effective and safe treatment option for managing symptoms associated with uterine myomatosis, offering a non-invasive approach to assess excessive menstrual bleeding and serving as a fertility-sparing option before surgery.

This therapy expands treatment options for reproductive medicine specialists, allowing for a combination of pharmacological and surgical interventions, which can enhance the effectiveness of treatments and improve the quality of life for women suffering from myomatosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix combination therapy and symptoms of uterine myomatosis - selected case reports of indication spectrum and treatment outcomes. Hudeček, R., Klát, J., Pohl, K., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Relugolix combination therapy in European women with symptomatic uterine fibroids: a subgroup analysis from the randomized phase 3 LIBERTY pivotal trials. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

LIBERTY randomized withdrawal study: relugolix combination therapy for heavy menstrual bleeding associated with uterine fibroids. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Development of relugolix combination therapy as a medical treatment option for women with uterine fibroids or endometriosis. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Relugolix combination therapy in Black/African American women with symptomatic uterine fibroids: LIBERTY Long-Term Extension study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Relugolix, a novel oral gonadotropin-releasing hormone antagonist, in the treatment of pain symptoms associated with uterine fibroids: a randomized, placebo-controlled, phase 3 study in Japanese women. [2020]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

Relugolix combination therapy and symptoms of uterine myomatosis - selected case reports of indication spectrum and treatment outcomes. [2023]