Relugolix Combination Therapy for Endometriosis

Overseen By Whitney Pollard, BS

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

Trial Summary

What is the purpose of this trial?

The goal of this investigator-initiated single-site clinical trial is to compare the overall quality of life of participants taking Relugolix combination therapy (Rel-CT) following excisional surgery for endometriosis to participants that do not take Rel-CT following the same surgery. Rel-CT is an FDA approved form of medical treatment for endometriosis. It is known to work in treating endometriosis pain. However, investigators do not know whether or not there is a benefit to beginning Rel-CT immediately following surgery. This study will test if patients who take Rel-CT after surgery have better quality of life and less chance the endometriosis comes back, requiring additional surgery. The main question it aims to answer is: - Does taking Rel-CT following excisional surgery for endometriosis result in higher Endometriosis Health Profile 30 (EHP-30) scores, indicating a positive impact on overall health-related quality of life and well-being? Participants will: * Be randomly assigned to one of two treatment groups. One treatment group will take study drug Rel-CT after having excisional surgery, and the other treatment group will just have the surgery alone. * Be asked to complete questionnaires, called the Endometriosis Health Profile 30 (EHP-30) at 4 timepoints. The first time is before surgery, then at follow-up visits at 1 month, 3 months, and 6 months. The survey has 30 questions that ask about pain, control, powerlessness, emotional well-being, social support, and self-image. Researchers will compare the two treatment groups (Rel-CT and non Rel-CT) to see if there is a change in EHP-30 scores.

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.

What data supports the effectiveness of the drug Relugolix Combination Therapy for endometriosis?

Research shows that Relugolix, a drug that blocks certain hormones, effectively reduces pain associated with endometriosis. Studies have demonstrated that it works better than a placebo and is comparable to other treatments like leuprorelin, making it a promising option for managing endometriosis symptoms. ^{1 2 3 4 5}

Is Relugolix Combination Therapy safe for humans?

Relugolix has been studied for safety in treating conditions like endometriosis and uterine fibroids. While it can cause symptoms related to low estrogen levels, such as bone density loss and hot flashes, combining it with other hormones helps reduce these risks, making it generally safe for longer-term use. ^{1 2 4 5 6}

How does relugolix combination therapy differ from other drugs for endometriosis?

Relugolix combination therapy is unique because it is the first and only once-daily oral treatment that combines a GnRH receptor antagonist with estradiol and norethindrone acetate to manage endometriosis pain while minimizing side effects like bone density loss, which are common with other treatments. ^{2 4 7 8 9}

Research Team

Jordan Klebanoff, MD

Principal Investigator

Main Line Health

Eligibility Criteria

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.

English or Spanish is not my first language.

My surgery did not show any signs of endometriosis.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

References

1. United States 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. [2021]

2. United States 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. [2022]

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

Combination GnRH antagonists for endometriosis: Balancing efficacy with side effects. [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. 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]

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. England 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). [2022]

8. England pubmed.ncbi.nlm.nih.gov

A Plain Language Summary to learn about relugolix combination therapy for the treatment of pain associated with endometriosis. [2023]

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

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