Pre-IVF GnRH Antagonist for Endometriosis-related Infertility

(PREGnant Trial)

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

103 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Elagolix for endometriosis-related infertility?

Elagolix has been shown to significantly reduce pain associated with endometriosis, which is a condition that can contribute to infertility. This drug is approved for managing moderate to severe endometriosis pain, suggesting it may help improve conditions related to endometriosis, potentially benefiting fertility. ^{1 2 3 4 5}

Is Elagolix safe for humans?

Elagolix has been approved by the FDA for managing pain associated with endometriosis, indicating it has been evaluated for safety in humans. It is generally considered safe, but like any medication, it may have side effects, which healthcare providers can discuss with you. ^{4 6 7 8 9}

How is the drug Elagolix unique for treating endometriosis-related infertility?

Elagolix is unique because it is an oral medication that works as a non-peptide GnRH antagonist, which means it blocks certain hormones to reduce pain and symptoms associated with endometriosis, unlike other treatments that often require injections. ^{1 4 5 9 10}

What is the purpose of this trial?

This trial tests a pill that helps women with endometriosis who are undergoing IVF. These women often have lower success rates with IVF, and the pill helps manage hormone levels to improve their chances of having a baby.

Research Team

Hugh Taylor, MD

Principal Investigator

Yale University

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

Abisola Tepede, PharmD

Principal Investigator

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

Heping Zhang, PhD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

References

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

Elagolix, an Oral GnRH Antagonist for Endometriosis-Associated Pain: A Randomized Controlled Study. [2022]

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

Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies. [2019]

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

Ultralong administration of gonadotropin-releasing hormone agonists before in vitro fertilization improves fertilization rate but not clinical pregnancy rate in women with mild endometriosis: a prospective, randomized, controlled trial. [2020]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Elagolix: First Global Approval. [2019]

5. England 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. [2022]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Elagolix in Healthy Women and Women with Endometriosis. [2019]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Real-World Characterization of Women with Diagnosed Endometriosis Initiating Therapy with Elagolix Using a US Claims Database. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Synthesis of [H-3]- and [C-14]-labeled elagolix. [2022]

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

Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix. [2022]