Elagolix for Endometriosis

(PREGnant Trial)

Recruiting at 4 trial locations

Overseen By Heping Zhang, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: Yale University

Must be taking: GnRH antagonists

Must not be taking: GnRH agonists, Medroxyprogesterone, Aromatase inhibitors, 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

297 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the medication Elagolix can improve live birth rates for women with endometriosis undergoing IVF. It involves two groups: one taking Elagolix and the other a placebo (sugar pill). Women planning to undergo IVF and diagnosed with endometriosis are suitable candidates for this trial. The goal is to determine if those taking Elagolix achieve higher IVF success rates compared to those who do not. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting, such as depot GnRH agonists, depot medroxyprogesterone acetate, and continuous oral progestins, among others. However, if you are in the standard of care arm, you may not need to meet these criteria. It's best to discuss your specific medications with the trial team.

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

Studies have shown that elagolix is generally well-tolerated. Earlier research identified the most common serious side effects as appendicitis (0.3%), stomach pain (0.2%), and back pain (0.2%). Long-term use of elagolix did not reveal any new safety concerns. This safety information comes from studies with many participants, ensuring reliable results. The FDA has approved elagolix for treating endometriosis, indicating its safety for this condition. Understanding these findings can help prospective trial participants make more informed decisions. ^{1 2 3 4 5}

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

Elagolix is unique because it targets endometriosis by acting as a GnRH antagonist, which helps to reduce the hormone levels that fuel the growth of endometrial tissue. Unlike standard treatments like hormonal birth control or surgery, Elagolix offers a non-invasive oral option that can provide relief without the need for long-term hormonal suppression or surgical intervention. Researchers are excited about Elagolix because it has the potential to offer quicker symptom relief and improved quality of life for patients with endometriosis compared to current therapies.

What evidence suggests that Elagolix might be an effective treatment for endometriosis?

Studies have shown that elagolix effectively reduces pain caused by endometriosis. Research indicates it can lower menstrual pain by up to 75% and non-menstrual pain by 50%–60%, suggesting significant relief for women with endometriosis. In this trial, participants will receive either elagolix or a placebo to assess its effects on live birth rates during IVF. Although the current trial focuses on live birth rates, elagolix's success in easing endometriosis symptoms suggests potential benefits in this new area. Overall, many patients have experienced significant relief from endometriosis-related pain with elagolix. ^{5 6 7 8 9}

Who Is on the Research Team?

Hugh Taylor, MD

Principal Investigator

Yale University

Heping Zhang, PhD

Principal Investigator

Yale University

Nanette Santoro, MD

Principal Investigator

University of Colorado, Denver

Emily Jungheim, MD

Principal Investigator

Northwestern University

Steven Young, MD, PhD

Principal Investigator

Duke University

Jim Segars, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for women with endometriosis who are struggling to get pregnant and planning to undergo IVF. Participants should not have received any hormonal treatments within the last three months.

Inclusion Criteria

Women who plan to undergo IVF for treatment of infertility

My AMH level is above 0.5ng/ml, or I have a high-quality blastocyst for FET.

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

Exclusion Criteria

Number of previous IVF/ICSI attempts ≥3 unsuccessful (negative pregnancy test)

Untreated abnormal prolactin or TSH

I have been taking oral progestins for the last month.

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 live birth rate and other pregnancy outcomes

Up to 15 months

Regular follow-up visits for pregnancy monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Elagolix

Trial Overview The study tests if taking a GnRH antagonist called Elagolix before starting IVF can increase the chances of giving birth. Women in the trial will either receive Elagolix or a placebo (a pill without active medication).

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 the participants 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+

University of North Carolina

Collaborator

Trials

174

Recruited

1,457,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

Elagolix, a medication for managing endometriosis and uterine fibroids, was studied in a large population of 2168 women across 13 clinical trials, showing that its pharmacokinetics are consistent and do not require dose adjustments based on patient-related factors.

The study found that only body weight and a specific genetic factor had minor effects on the drug's absorption and distribution, indicating that the standard dosage of 300 mg twice daily remains effective and safe for women with heavy menstrual bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Elagolix in Combination with Low-Dose Estradiol/Norethindrone Acetate in Women with Uterine Fibroids. Beck, D., Winzenborg, I., Liu, M., 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]

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]

A novel and sensitive LC-MS-compatible method was developed to quantify organic impurities in elagolix sodium tablets, achieving significant resolution of impurities in just 46 minutes.

The method demonstrated high stability and specificity, effectively identifying major degradation products under various stress conditions, making it suitable for quality control in pharmaceutical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LC-MS-Compatible Chromatographic Method for Quantification of Potential Organic Impurities of Elagolix Sodium in Tablet Dosage Form with Identification of Major Degradation Products. Desai, P., Prajapati, R., Chokshi, A.[2023]

Elagolix effectively suppresses ovulation in a dose-dependent manner, with the lowest ovulation rates observed at higher doses (27% at 300 mg BID), indicating its potential as a contraceptive method for women with endometriosis.

The treatment also leads to significant suppression of key hormones like luteinizing hormone and estradiol, but does not affect ovarian reserve, suggesting it may be a safe option for managing endometriosis-associated pain without compromising fertility in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elagolix Suppresses Ovulation in a Dose-Dependent Manner: Results From a 3-Month, Randomized Study in Ovulatory Women. Archer, DF., Ng, J., Chwalisz, K., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38955323/

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 ...

2. ajog.org ajog.org/article/S0002-9378(24)00731-2/fulltext

Efficacy, tolerability, and bone density outcomes of elagolix ... The results from the current study indicate that endometriosis-associated pain treatment with ELA+AB therapy provides efficacious reductions in ...

3. orilissa.com orilissa.com/hcp/clinical-data/study-design

ORILISSA® (elagolix) Clinical Study Design The efficacy, safety, and tolerability of ORILISSA were demonstrated in the largest endometriosis Phase 3 study program to date (N=1686) · Endpoints ...

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

An Evidence-Based Review of Elagolix for the Treatment of ... Studies up to 12 months long showed continued efficacy and reduction in dysmenorrhea of up to 75%, with 50%–60% reduction in non-menstrual pain. Elagolix was ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1553465021008517

Real-World Effectiveness of Elagolix in Reducing ... This real-world study demonstrated that Elagolix had a beneficial impact by improving endometriosis-associated pain outcomes at 6M, consistent with previously ...

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/29889764/

Long-Term Outcomes of Elagolix in Women With ... The safety was consistent with reduced estrogen levels and no new safety concerns were associated with long-term elagolix use.

8. 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 ...

9. 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.