Pre-IVF GnRH Antagonist for Endometriosis-related Infertility

(PREGnant Trial)

No longer recruiting at 6 trial locations

Overseen By James Segars

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: Yale University

Must be taking: GnRH antagonists

Must not be taking: Depot GnRH agonists, MPA, Hormonal contraceptives

Disqualifiers: Pregnancy, Malignancy, Osteoporosis, Cirrhosis, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial researches a new treatment for women with endometriosis who face infertility and plan to undergo IVF (in vitro fertilization). The treatment, Elagolix, is taken as a pill and may improve the chances of a live birth compared to those not receiving it. Participants will take either Elagolix or a placebo (a harmless pill with no effect) before starting IVF. Women diagnosed with endometriosis and planning IVF might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires stopping certain medications like depot GnRH agonists, hormonal contraceptives, and others before starting, unless you are in the standard of care group. It's best to discuss your specific medications with the trial team to see if any changes are needed.

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

Research has shown that elagolix is generally safe for most people. In earlier studies, serious side effects like appendicitis, stomach pain, and back pain occurred in less than 1% of those taking the drug. The FDA has approved elagolix for treating pain related to endometriosis, confirming its safety for that purpose.

Although elagolix can cause low estrogen effects, such as hot flashes, when used alone, these effects are usually manageable. Overall, evidence indicates that elagolix has a good safety record for its intended use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometriosis-related infertility?

Researchers are excited about Elagolix for endometriosis-related infertility because it offers a novel approach by using a GnRH antagonist to directly lower hormone levels related to endometriosis. This is different from standard treatments like hormonal contraceptives or laparoscopic surgery, which either mask symptoms or require invasive procedures. Unlike these options, Elagolix is taken orally, making it a more convenient and less invasive option while specifically targeting the hormonal cause of endometriosis pain and dysfunction. By potentially improving fertility outcomes pre-IVF, Elagolix could provide a significant advantage for those struggling with infertility due to endometriosis.

What evidence suggests that this treatment might be an effective treatment for endometriosis-related infertility?

Research has shown that elagolix, an oral medication, can help manage pain from endometriosis. It reduces pelvic and menstrual pain, improving life for many women. Earlier studies found that elagolix eased symptoms more effectively than a placebo. The medication works by lowering certain hormones that cause endometriosis pain. In this trial, one group of participants will receive a 60-day course of elagolix before IVF, while another group will receive a placebo or continue with standard IVF care. Although researchers are still learning how this treatment affects live birth rates in IVF for women with endometriosis, its success in reducing symptoms suggests it might also improve reproductive outcomes. ^{4 5 6 7 8}

Who Is on the Research Team?

Hugh Taylor, MD

Principal Investigator

Yale University

Abisola Tepede, PharmD

Principal Investigator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

David Weinberg, PhD

Principal Investigator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Nanette Santoro, MD

Principal Investigator

University of Colorado, Denver

Emily Jungheim, MD

Principal Investigator

Northwestern University

Steven Young, MD, PhD

Principal Investigator

Duke University

Heping Zhang, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

Women aged 18-40 with diagnosed endometriosis planning IVF can join. They must have a BMI of 18-40, no severe uterine issues, at least one healthy ovary, and an AMH level over 0.5ng/ml within the last year. Exclusions include recent use of certain contraceptives or hormone treatments, more than two failed IVF attempts, untreated reproductive tract conditions, certain cancers in the past five years, planned pelvic surgeries during the trial period.

Inclusion Criteria

My endometriosis was confirmed by surgery or pathology within the last 10 years, or I have an ovarian cyst linked to endometriosis.

You are a woman who is planning to have in vitro fertilization (IVF) to help with infertility.

You are willing and able to comply with trial procedures, including reporting of obstetrical outcomes after delivery.

Exclusion Criteria

I have used hormone therapy for fertility within the last 6 months.

I have had fractures from minor injuries or have risk factors for weak bones.

You have had thoughts of hurting yourself or suicide within the past year, based on what you've said or what's written in your medical records.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-IVF Treatment

Participants receive a 60-day course of oral GnRH antagonist or placebo

8 weeks

Regular visits for medication adherence and monitoring

IVF Procedure

Participants undergo in vitro fertilization-embryo transfer (IVF-ET)

4-6 weeks

Multiple visits for egg retrieval and embryo transfer

Follow-up

Participants are monitored for pregnancy outcomes and complications

Up to 15 months

Regular visits for pregnancy monitoring and outcome assessment

What Are the Treatments Tested in This Trial?

Interventions

• Elagolix

Trial Overview The study is testing if taking Elagolix (a GnRH antagonist) before starting IVF improves live birth rates for women with endometriosis compared to those who don't take it but undergo standard IVF treatment.

How Is the Trial Designed?

Group I: Pre-IVF Treatment with 60 day course of Placebo or SOC IVF Experimental Treatment 1 Intervention

For those who agree to be randomized, subjects will be randomized to placebo, BID. The medication will be taken orally and subjects will be counseled to take the medication at the same time each day. This arm will also include participants who want to continue their ongoing or planned IVF and follow standard of care (SOC) (SOC IVF) if they do not want to delay the IVF procedure.

Group II: Pre-IVF Treatment with 60 day course of oral GnRH antagonist Active Control 1 Intervention

For those who agree to be randomized, subjects will be randomized to elagolix 200mg BID. The medication will be taken orally and subjects will be counseled to take the medication at the same time each day. This arm will also include participants who do not want to be randomized while choose elagolix.

Elagolix is already approved in United States for the following indications:

Approved in United States as Orilissa for:

• Management of moderate to severe pain associated with endometriosis

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

University of North Carolina

Collaborator

Trials

174

Recruited

1,457,000+

Published Research Related to This Trial

Elagolix, a GnRH receptor antagonist, significantly reduces dysmenorrhea and non-menstrual pelvic pain in women with moderate to severe endometriosis, based on pooled data from over 1600 participants in two 6-month phase 3 studies.

The treatment was effective across various subgroups, with significant improvements in pain reported at 3 months and enhancements in health-related quality of life, indicating its broad applicability for different women with endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reductions in endometriosis-associated pain among women treated with elagolix are consistent across a range of baseline characteristics reflective of real-world patients. Abrao, MS., Surrey, E., Gordon, K., et al.[2022]

After 12 months of treatment with elagolix, 52.1% of women taking 150 mg once daily and 78.2% taking 200 mg twice daily reported significant reductions in dysmenorrhea, indicating its efficacy in managing endometriosis-associated pain.

The treatment was generally safe, with no new safety concerns identified; however, some participants experienced decreased bone mineral density and increased lipid levels, which are consistent with reduced estrogen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies. Surrey, E., Taylor, HS., Giudice, L., et al.[2019]

Elagolix (Orilissa) is an FDA-approved oral treatment for endometriosis-related pain that works by blocking gonadotropin-releasing hormone receptors, leading to reduced hormone levels and decreased inflammation of endometrial tissue.

This medication is significant for the estimated 10% of reproductive-age women affected by endometriosis, as it addresses symptoms like chronic pelvic pain and dysmenorrhea, although it also has contraindications and potential adverse effects that healthcare providers need to consider.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elagolix as a Novel Treatment for Endometriosis-Related Pain. Fantasia, HC.[2020]

Elagolix (ORILISSA™) is an FDA-approved oral medication for managing moderate to severe pain from endometriosis, based on positive results from two phase III trials.

It is currently being tested in additional phase III trials for both endometriosis and heavy menstrual bleeding associated with uterine fibroids, indicating its potential for broader applications in treating reproductive hormone-dependent disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elagolix: First Global Approval. Lamb, YN.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04039204

Study Details | NCT04039204 | Elagolix for Fertility ... Studies suggest that undiagnosed endometriosis results in poor reproductive outcomes in the setting of In Vitro Fertilization and Embryo Transfer (IVF-ET).

2. sciencedirect.com sciencedirect.com/science/article/pii/S0002937824007312

Efficacy, tolerability, and bone density outcomes of elagolix ... We report 12-month results on efficacy of elagolix with add-back therapy vs placebo in reducing dysmenorrhea, nonmenstrual pelvic pain, dyspareunia, and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8064963/

A Clinician's Guide to the Treatment of Endometriosis with ... In clinical trials, elagolix has been shown to reduce pelvic pain (including dysmenorrhea, NMPP, and dyspareunia), improve quality of life, and decrease the ...

4. fertstert.org fertstert.org/article/S0015-0282(21)01152-3/fulltext

REAL-WORLD EFFECTIVENESS OF ELAGOLIX IN ... This real-world, patient-reported data demonstrates that elagolix had a positive impact on women's quality of life at 3M and 6M.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7901127/

An Evidence-Based Review of Elagolix for the Treatment of ... Elagolix phase 3 trials were effective in improving both dysmenorrhea and non-menstrual pain associated with endometriosis compared to placebo in 6 months. With ...

6. orilissa.com orilissa.com/hcp/clinical-data/safety-information-and-tolerability

Safety and Tolerability Profile of ORILISSA® (elagolix) The most common serious adverse events reported with ORILISSA in ELARIS EM-1 and EM-2 included appendicitis (0.3%), abdominal pain (0.2%), and back pain (0.2%).

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39096881/

The short- and mid-term efficacy and safety of elagolix in ... The efficacy of elagolix in reducing pain in premenopausal women with endometriosis has been demonstrated over the short- to mid-term.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00973973

NCT00973973 | Efficacy and Safety Study of Elagolix in ... The purpose of this study is to evaluate elagolix (NBI-56418) compared to placebo for its effects on endometriosis related pelvic pain and its safety.