Relugolix Combination Therapy for Endometriosis

Overseen By Sara Burke, MPH

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Main Line Health

Must not be taking: Hormonal suppression

Disqualifiers: Thrombotic disorder, Pregnancy, Osteoporosis, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 6 months

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether Relugolix combination therapy (Rel-CT) after endometriosis surgery can improve quality of life and reduce the likelihood of recurrence. Endometriosis often causes pain and other symptoms, and the study aims to determine if Rel-CT can alleviate these issues when initiated immediately post-surgery. Participants will be divided into two groups: one will receive Rel-CT after surgery, and the other will not. Ideal candidates for this trial are those planning endometriosis surgery and not seeking pregnancy within the next six months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using any hormonal treatments for endometriosis, you must stop them at least 4 weeks before the surgery.

Is there any evidence suggesting that Relugolix combination therapy is likely to be safe for humans?

Previous studies have shown that relugolix combination therapy (Rel-CT) is well-tolerated. Research indicates that most patients experienced less endometriosis pain without major issues. For up to two years, women treated with Rel-CT reported better pain management and overall function.

One study found that taking Rel-CT daily significantly reduced endometriosis-related pain and was generally well-tolerated. However, like any medication, some people might experience side effects, although serious problems were rare.

Rel-CT is already approved by the FDA for treating endometriosis pain, indicating a known safety profile in humans. While not risk-free, it has been thoroughly tested for safety. Always discuss any concerns with a healthcare provider before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for endometriosis?

Researchers are excited about relugolix combination therapy for endometriosis because it offers a new approach in managing symptoms. Unlike standard treatments that often rely on continuous hormonal therapies like gonadotropin-releasing hormone (GnRH) agonists, relugolix works as a GnRH antagonist, providing a different mechanism that directly blocks hormone signals responsible for endometriosis pain. Additionally, the combination with estradiol and norethindrone acetate helps minimize bone density loss, a common side effect of hormone treatments. This approach not only targets the root cause of symptoms but also aims to improve the overall quality of life for patients with fewer side effects.

What is the effectiveness track record for Relugolix in treating endometriosis?

Research has shown that Relugolix combination therapy (Rel-CT), which participants in this trial may receive, effectively treats endometriosis. Studies have found that Rel-CT significantly reduces pain associated with endometriosis, including both menstrual and non-menstrual pain. This treatment also lessens pain during sex and improves daily functioning for women with the condition. Additionally, Rel-CT improved scores on the Endometriosis Health Profile 30 (EHP-30), a health survey measuring pain and well-being. These findings suggest that Rel-CT can enhance the quality of life for people with endometriosis. ^{3 4 5 6 7}

Who Is on the Research Team?

Jordan Klebanoff, MD

Principal Investigator

Main Line Health

Are You a Good Fit for This Trial?

This trial is for individuals who have undergone excisional surgery for endometriosis. It's designed to determine if taking Relugolix combination therapy (Rel-CT) post-surgery improves their quality of life compared to just having the surgery alone.

Exclusion Criteria

I cannot take Rel-CT due to health reasons.

My surgery did not show any signs of endometriosis.

English or Spanish is not my first language.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo excisional surgery for endometriosis

1 day

1 visit (in-person)

Treatment

Participants receive Rel-CT or no study drug following surgery

6 months

4 visits (in-person) at 1 month, 3 months, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

3 visits (in-person) at 1 month, 3 months, and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Relugolix

Trial Overview

The study compares two groups: one receiving Relugolix combination therapy after endometriosis surgery, and another undergoing only the surgery. The main focus is on whether Rel-CT leads to better health-related quality of life as measured by EHP-30 scores over time.

How Is the Trial Designed?

Group I: Rel-CT Active Control 1 Intervention

40 mg relugolix, 1 mg estradiol, 0.5 mg norethindrone acetate, one tablet daily for 6 months

Group II: no study drug Active Control 1 Intervention

no study drug

Who Is Running the Clinical Trial?

Main Line Health

Lead Sponsor

Trials

22

Recruited

6,900+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Sumitomo Pharma America, Inc.

Industry Sponsor

Trials

244

Recruited

51,500+

Jatin Shah

Sumitomo Pharma America, Inc.

Chief Medical Officer since 2024

MD from an unspecified institution

Tsutomu Nakagawa

Sumitomo Pharma America, Inc.

Chief Executive Officer since 2024

MBA from Waseda University

Sumitomo Pharma Switzerland GmbH

Industry Sponsor

Trials

19

Recruited

6,900+

Published Research Related to This Trial

In two phase 3 trials involving 1,261 women with endometriosis, relugolix combination therapy significantly reduced both dysmenorrhoea and non-menstrual pelvic pain compared to placebo, with 75% of participants responding positively to treatment.

The therapy was well tolerated, with common side effects including headache and hot flushes, and it also led to a decrease in opioid use, highlighting its potential as a long-term treatment option for endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). Giudice, LC., As-Sanie, S., Arjona Ferreira, JC., et al.[2022]

In a study involving 1261 women with moderate to severe endometriosis, those taking relugolix combination therapy experienced significantly less pelvic and groin pain during and between menstrual periods compared to those on a placebo, with 75% reporting pain relief during periods and 59% between periods after 24 weeks.

Relugolix combination therapy was found to be safe, with minimal impact on bone mineral density and common side effects including headaches and hot flushes, indicating it is a viable treatment option for women without major medical issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Plain Language Summary to learn about relugolix combination therapy for the treatment of pain associated with endometriosis. Giudice, LC., As-Sanie, S., Arjona Ferreira, JC., 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 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]

In a Phase 3 study involving women with endometriosis-associated pain, relugolix (40 mg daily) was found to be noninferior to leuprorelin in reducing pelvic pain over 24 weeks, with similar effectiveness in decreasing ovarian endometriomas.

Both medications had comparable safety profiles, but relugolix allowed for earlier return of menses, which could be advantageous for women planning to conceive after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain compared with leuprorelin in Japanese women: a phase 3, randomized, double-blind, noninferiority study. Harada, T., Osuga, Y., Suzuki, Y., et al.[2022]

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]

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 12-week study involving 399 premenopausal women with endometriosis, relugolix demonstrated significant pain relief, with the 40 mg dose showing the greatest reduction in pelvic pain compared to placebo and similar efficacy to leuprorelin.

Relugolix was generally well tolerated, although it did have side effects such as hot flushes and changes in menstrual patterns, with a dose-dependent decrease in bone mineral density observed, similar to those seen with leuprorelin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain in a dose-response manner: a randomized, double-blind, placebo-controlled study. Osuga, Y., Seki, Y., Tanimoto, M., et al.[2021]

Endometriosis affects approximately 1 in 10 women and is associated with chronic pain, highlighting the need for improved medical treatments.

The study focuses on trials of a combined hormone replacement therapy (HRT) and GnRH antagonist (Relugolix) as a potential treatment for pain associated with endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination GnRH antagonists for endometriosis: Balancing efficacy with side effects. Whitaker, LHR., Saraswat, L., Horne, AW.[2023]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10905503/

Two-year efficacy and safety of relugolix combination therapy ...

For up to 2 years, treatment with relugolix CT improved menstrual and non-menstrual pain, dyspareunia, and function in women with endometriosis.

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myfembreehcp.com

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MYFEMBREE® Endo Efficacy Data

Co-primary endpoints were the proportion of women who achieved a reduction from baseline in period pain 0-10 NRS scores of ≥2.8 points over the last 35 days of ...

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thelancet.com

thelancet.com/article/s0140-6736%2822%2900622-5/fulltext

Once daily oral relugolix combination therapy versus ...

Once-daily relugolix combination therapy significantly improved endometriosis-associated pain and was well tolerated. This oral therapy has the ...

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frontiersin.org

frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1650579/full

Relugolix's impact on endometriosis-associated pain and ...

Conclusion: Oral relugolix significantly improves EHP-30 pain domain scores and patient response rates in endometriosis, particularly when compared to placebo.

5.

ajog.org

ajog.org/article/S0002-9378(23)00600-2/fulltext

LIBERTY randomized withdrawal study: relugolix ...

Relugolix combination therapy (40 mg relugolix, 1 mg estradiol, 0.5 mg norethindrone acetate) reduced menstrual blood loss volume and pain among women with ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0015028225002511

Efficacy and safety of relugolix combination therapy in ...

Amenorrhea was achieved in 64.9% of women with adenomyosis treated with relugolix combination therapy and in 6.9% of women treated with placebo. The least ...

7.

accessdata.fda.gov

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

MYFEMBREE® (relugolix, estradiol, and norethindrone ...

There are insufficient data to conclude whether the presence of uterine fibroids or endometriosis reduces the likelihood of achieving pregnancy or increases the ...