Relugolix-Combination Therapy for Pelvic Pain

Overseen By Kevin Hellman, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Endeavor Health

Disqualifiers: Diabetes, Migraines, Osteoporosis, Smoking, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Relugolix-Combination Therapy for pelvic pain?

Research shows that Relugolix-Combination Therapy effectively reduces pain and heavy menstrual bleeding in women with uterine fibroids and endometriosis, which are conditions that can cause pelvic pain. The therapy is well tolerated and helps maintain bone health over time. ^{1 2 3 4 5}

How is relugolix combination therapy different from other drugs for pelvic pain?

Relugolix combination therapy is unique because it is an oral medication that combines relugolix, a gonadotropin-releasing hormone antagonist, with estradiol and norethindrone acetate to manage pelvic pain while preserving bone health, unlike other treatments that may lead to bone density loss. ^{1 3 4 5 6}

What is the purpose of this trial?

The mechanisms underlying variable efficacy of Relugolix-Combination Therapy (REL-CT) in mitigating unexplained pelvic pain will be evaluated with uterine imaging techniques and quantitative sensory testing.

Eligibility Criteria

This trial is for women with severe endometriosis (stage III-IV) or those with unexplained pelvic pain, both experiencing a certain level of pain over the past 6 months. Participants should not be overweight, have blood clotting issues, liver disorders, allergies to REL-CT ingredients, hormone-sensitive cancers, metal in their body that affects MRI scans, thyroid problems or other specific health conditions.

Inclusion Criteria

I have had pelvic pain not related to periods, averaging 2/10 or more, for the past 6 months without a known cause.

I have severe endometriosis and experience significant pelvic pain.

Exclusion Criteria

Intrauterine device use

My BMI is over 40.

I have a liver condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Relugolix-combination therapy for 6 months, starting within 7 days of their period

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Relugolix-Combination Therapy

Trial Overview The study tests Relugolix combination therapy's effectiveness on pelvic pain using advanced uterine imaging and sensory testing. It aims to understand why this treatment works well for some women but not others by looking at how their bodies respond differently.

Participant Groups

Group I: Idiopathic Pelvic Pain Experimental Treatment 1 Intervention

Participants with Idiopathic Pelvic Pain must: 1. Self-report an average non-menstrual pelvic pain rating of ≥ 4/10 (on a 0 to 10 Numeric Rating Scale) over the past 6 months. 2. Not have received a prior diagnosis attributed to a secondary cause (e.g., leiomyoma, endometriosis). Participants will be instructed to start taking Relugolix-combination therapy (40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate) within 7 days of their period starting, at the same time every day for the next 6 months.

Group II: Endometriosis: Experimental Treatment 1 Intervention

Participants with Endometriosis: 1. Must self-report an average non-menstrual pelvic pain rating of ≥ 4/10 (on a 0 to 10 Numeric Rating Scale) over the past 6 months. 2. Have a previously confirmed surgical diagnosis of stage III-IV endometriosis, indicating potential remission. Participants will be instructed to start taking Relugolix-combination therapy (40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate) within 7 days of their period starting, at the same time every day for the next 6 months.

Who Is Running the Clinical Trial?

Endeavor Health

Lead Sponsor

Trials

135

Recruited

742,000+

NorthShore University HealthSystem

Lead Sponsor

Trials

134

Recruited

740,000+

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

Findings from Research

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 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]

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 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]

References

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

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

2. 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]

3. 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]

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

Long-term Relugolix Combination Therapy for Symptomatic Uterine Leiomyomas. [2023]

5. 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]

6. 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]