Relugolix for Uterine Fibroids

Recruiting at 115 trial locations

Overseen By Clinical Trials at Myovant

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

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 All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 48 months

1000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called relugolix (a combination tablet) to assess its impact on bone health over four years. It focuses on women with heavy menstrual bleeding due to uterine fibroids or moderate-to-severe pain from endometriosis. The goal is to understand changes in bone mineral density, a measure of bone strength. The trial seeks premenopausal women diagnosed with either condition whose symptoms affect daily life. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the chance to contribute to the potential availability of a new treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the relugolix combination tablet is generally safe for treating uterine fibroids. In earlier studies, researchers tested this treatment on women experiencing heavy menstrual bleeding due to fibroids. Most participants tolerated the treatment well. Common side effects included headaches and hot flashes, which were usually mild.

Another study found that combining relugolix with hormones like estradiol and norethindrone reduced menstrual bleeding more effectively than a placebo. Importantly, this treatment helped maintain bone strength, crucial for long-term health.

Overall, evidence suggests that the relugolix combination tablet is both effective and well-tolerated for women with fibroids. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for uterine fibroids?

Relugolix is unique because it offers a new approach to managing uterine fibroids by combining relugolix with other hormone-balancing agents into a once-daily oral tablet. Unlike traditional treatments like surgery or GnRH agonists, which can have significant side effects or require invasive procedures, relugolix works by providing a balanced hormone suppression that reduces fibroid size and alleviates symptoms with a more convenient administration. Researchers are particularly excited about its potential to offer effective symptom relief with fewer side effects and without the need for injections or surgery.

What evidence suggests that this treatment might be an effective treatment for uterine fibroids?

Research shows that the relugolix combination tablet, which trial participants will receive, effectively treats symptoms of uterine fibroids. Studies have found that this treatment significantly reduces heavy menstrual bleeding in women with these fibroids. It also helps maintain healthy bones, crucial for long-term health. Additionally, evidence suggests that relugolix combination therapy eases painful periods in women with endometriosis. Overall, research supports its effectiveness in managing both heavy menstrual bleeding and pain related to these conditions. ^{3 5 6 7 8}

Who Is on the Research Team?

Myovant Medical Director

Principal Investigator

Myovant Sciences GmbH

Are You a Good Fit for This Trial?

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

Has a body mass index ≥ 18 kg/m^2

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Relugolix Combination Tablet

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.

How Is the Trial Designed?

Group I: Relugolix Combination Tablet Experimental Treatment 1 Intervention

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

Relugolix Combination Tablet is already approved in United States, European Union for the following indications:

Approved in United States as Myfembree for:

• Heavy menstrual bleeding associated with uterine fibroids
• Moderate to severe pain associated with endometriosis

Approved in European Union as Ryeqo for:

• Moderate to severe symptoms of uterine fibroids

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9684252/

Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate Relugolix + estradiol/norethisterone substantially reduced menstrual bleeding and improved several other symptoms in women with uterine fibroids-associated ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2008283

Treatment of Uterine Fibroid Symptoms with Relugolix ... Once-daily relugolix combination therapy resulted in a significant reduction in menstrual bleeding, as compared with placebo, and preserved bone mineral ...

3. myfembreehcp.com myfembreehcp.com/uf-efficacy-data/

Efficacy Data in UF | MYFEMBREE® (relugolix, estradiol, and ... Review the efficacy data of MYFEMBREE® for treating heavy menstrual bleeding due to uterine fibroids. See Safety Info and BOXED WARNING.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04756037

NCT04756037 | Study of the Safety and Contraceptive ... This is a single-arm, open-label, phase 3 study to assess the contraceptive efficacy of relugolix combination therapy.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11127801/

Relugolix/Estradiol/Norethisterone Acetate: A Review in ... Relugolix combination therapy significantly improved dysmenorrhoea and non-menstrual pelvic pain in premenopausal women with moderate to severe endometriosis.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12489269/

Safety and efficacy of relugolix combination therapy in ... Real-life clinical data support the use of relugolix-CT to treat symptomatic fibroids in isolation or combined with myomectomy. Keywords: ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/214846s002lbl.pdf

MYFEMBREE® (relugolix, estradiol, and norethindrone ... The safety of MYFEMBREE was evaluated in two placebo-controlled clinical trials, Study L1. (LIBERTY 1) and Study L2 (LIBERTY 2), in women with heavy menstrual ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0015028225002511

Efficacy and safety of relugolix combination therapy in ... Efficacy and safety of relugolix combination therapy in women with uterine fibroids and adenomyosis: subgroup analysis of LIBERTY 1 and LIBERTY 2. Author links ...