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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Relugolix-Combination Therapy to evaluate its effectiveness for women with pelvic pain. Special imaging and sensory tests will help determine why the treatment affects individuals differently. Participants will be divided into two groups: one for those with unexplained pelvic pain and another for those with endometriosis (a condition where tissue similar to the uterine lining grows outside the uterus). This trial may suit individuals who have experienced non-menstrual pelvic pain rated 4 or higher out of 10 over the past six months and either have endometriosis or lack a diagnosis for another cause of their pain. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that Relugolix-Combination Therapy is likely to be safe for humans?

Research has shown that Relugolix-Combination Therapy is generally well-tolerated. After two years of use, 95.3% of women reported little to no menstrual pain, demonstrating its effectiveness. Safety data from earlier studies indicate that many patients experience no serious side effects with this treatment.

In another study, 58% of patients with non-menstrual pelvic pain responded positively to the therapy. Relugolix-Combination Therapy, which includes relugolix, estradiol, and norethindrone, also treats heavy menstrual bleeding caused by fibroids, further supporting its safety. These studies suggest that the therapy is safe for most people, though some side effects may occur. Always consult a doctor to determine if it is suitable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pelvic pain?

Relugolix-combination therapy is unique because it combines relugolix, a GnRH receptor antagonist, with estradiol and norethindrone acetate to specifically target pelvic pain conditions like idiopathic pelvic pain and endometriosis. Unlike standard treatments that often rely on surgical interventions or long-term use of hormonal therapies, relugolix offers a non-invasive option that directly blocks the receptors responsible for signaling pain and inflammation associated with these conditions. Researchers are excited because this combination not only alleviates pain but also aims to maintain hormonal balance, potentially reducing the side effects commonly associated with other hormonal treatments.

What evidence suggests that Relugolix-Combination Therapy might be an effective treatment for pelvic pain?

This trial will evaluate Relugolix-Combination Therapy for pelvic pain in participants with either idiopathic pelvic pain or endometriosis. Studies have shown that Relugolix-Combination Therapy effectively reduces pelvic pain and heavy menstrual bleeding in conditions like endometriosis and uterine fibroids. For women with endometriosis, this therapy improved pain and overall quality of life for up to two years. Specifically, up to 88.6% of participants experienced significant improvements over time. This treatment combines relugolix with two other medications, estradiol and norethindrone acetate, which work together to manage pain and bleeding. Taken as a daily oral pill, it is easy to use, and most people have tolerated it well. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

Citations

1. 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.

2. 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 ...

3. 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 ...

4. obgproject.com obgproject.com/2024/11/14/rct-extension-study-does-relugolix-combination-therapy-improve-quality-of-life-for-women-with-endometriosis/

RCT Extension Study: Does Relugolix Combination ... CONCLUSION: Relugolix combined therapy was associated with improvements in endometriosis-related pain up to 104 weeks and health-related QoL ...

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

LIBERTY randomized withdrawal study: relugolix ... At week 104, 69.8% of women on relugolix combination therapy maintained menstrual blood loss volume <80 mL vs 11.8% in the placebo group ( ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03204331

SPIRIT 2: Efficacy and Safety Study of Relugolix in Women ... The purpose of this study is to determine the benefit and safety of relugolix 40 milligrams (mg) once daily, co-administered with low-dose estradiol (E2) and ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/relugolix-estradiol-and-norethindrone-oral-route/description/drg-20516721

Relugolix, estradiol, and norethindrone (oral route) Relugolix, estradiol, and norethindrone combination is used to manage heavy menstrual bleeding caused by uterine leiomyomas (fibroids) in premenopausal women.

8. link.springer.com link.springer.com/article/10.1007/s40265-024-02018-3

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.