Elagolix + COC for Endometriosis

(ELARIS EM-COC Trial)

Not currently recruiting at 219 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Combined oral contraceptives

Disqualifiers: Pregnancy, Hysterectomy, Osteoporosis, others

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 explores whether elagolix, combined with birth control pills (also known as combined oral contraceptives or COCs), can effectively reduce severe pain from endometriosis compared to a placebo (a pill with no active drug). Endometriosis occurs when tissue similar to the uterine lining grows outside the uterus, causing painful periods and affecting daily life. Women surgically diagnosed with endometriosis and experiencing moderate to severe pain might be suitable for this trial. Participants will join one of three groups to receive different treatments for up to 18 months and must attend regular check-ups. 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 protocol does not specify if you must stop taking your current medications. However, you must agree to use non-hormonal contraception during certain periods of the study, which might affect your current medication use.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that elagolix, the drug tested in this trial, is generally well-tolerated. In previous studies, serious side effects such as appendicitis, abdominal pain, and back pain were rare, affecting fewer than 1% of participants. Among over 2,000 people who took elagolix, four reports of suicidal thoughts occurred.

When combined with birth control pills, elagolix might increase the likelihood of experiencing side effects related to the contraceptive, similar to those from ethinyl estradiol, a common ingredient in birth control. However, the FDA has already approved elagolix for treating endometriosis pain, indicating its safety for this condition.

This trial is in a later stage, suggesting the treatment has already demonstrated reasonable safety in earlier tests. Researchers will closely monitor participants for any side effects during the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Elagolix for endometriosis because it offers a new approach compared to standard treatments like NSAIDs, hormonal therapies, and surgery. Elagolix is a non-peptide small molecule that acts as a GnRH antagonist, which helps to reduce estrogen levels and alleviate pain from endometriosis. This contrasts with the standard use of hormonal therapies, which often come with a wider range of side effects. Additionally, the combination of Elagolix with a combined oral contraceptive could provide a balanced approach, managing symptoms while potentially minimizing hormonal fluctuations. This dual-action strategy has the potential to improve quality of life for patients who have not found relief with existing treatments.

What evidence suggests that this trial's treatments could be effective for endometriosis?

Research has shown that elagolix effectively reduces pain from endometriosis, including painful periods and other pelvic pain. In studies, up to 75% of women reported less menstrual pain, and about 50-60% experienced reduced non-menstrual pain. Elagolix is already approved for treating moderate to severe endometriosis pain. In this trial, participants will receive either elagolix alone, elagolix with combined oral contraceptives (COC), or a placebo. When combined with birth control pills, elagolix has shown positive results in real-world settings, with over 70% of women reporting improved pain relief. These findings suggest that elagolix, either alone or with birth control pills, could be a promising option for managing endometriosis pain. ^{6 7 8 9 10}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for adult women who have endometriosis with moderate to severe pain and are suitable candidates for combined oral contraceptives (COCs). They must not be pregnant, breastfeeding, or planning pregnancy until the study ends. Participants should not have had a hysterectomy or oophorectomy, osteoporosis, other metabolic bone diseases, or any chronic pain conditions that could affect their pain assessment.

Inclusion Criteria

Documented surgical confirmation of endometriosis and associated moderate to severe pain.

Have you been surgically diagnosed with Endometriosis and have documentation?

Are your menstrual cycles regular, meaning every 21-35 days?

Exclusion Criteria

Are you currently breastfeeding, pregnant, or planning a pregnancy.

You have been diagnosed with PCOS

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-Blind Treatment

Participants receive double-blind elagolix or placebo in combination with COC for 3 months

3 months

Regular visits at a hospital or clinic

Open-Label Treatment

All participants receive open-label elagolix in combination with COC for 15 months

15 months

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Combined Oral Contraceptive (COC)
• Elagolix
• Placebo for COC
• Placebo for Elagolix

Trial Overview

The study tests how well elagolix works with COCs compared to a placebo in managing painful periods due to endometriosis. About 800 participants will be randomly assigned to one of three groups: two receiving different treatments and one receiving a placebo. After three months on varied regimens, all participants will receive elagolix with COCs from Month 4 through Month 18.

How Is the Trial Designed?

Group I: Double-Blind: Elagolix + COC Experimental Treatment 2 Interventions

Participants will receive double-blind elagolix in combination with COC (combined oral contraceptive) on Day 1 for 3 months. At month 4, participants will receive open-label elagolix in combination with COC for 15 months. Participants will be followed-up for up to 12 months.

Group II: Double-Blind: Elagolix Experimental Treatment 2 Interventions

Participants will receive double-blind Elagolix on Day 1 for 3 months. At month 4, participants will receive open-label elagolix in combination with COC (combined oral contraceptive) for 15 months. Participants will be followed-up for up to 12 months.

Group III: Double-Blind: Placebo Placebo Group 3 Interventions

Participants will receive double-blind placebo on Day 1 for 3 months. At month 4, participants will receive open-label elagolix in combination with COC (combined oral contraceptive) for 15 months. Participants will be followed-up for up to 12 months.

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?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

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]

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 (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]

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, 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]

In two phase III trials involving patients with moderate to severe endometriosis pain, elagolix significantly improved health-related quality of life (HRQOL) as measured by the EHP-30 questionnaire, with the 200 mg dose showing the greatest improvements across multiple subscales compared to placebo.

Both doses of elagolix (150 mg and 200 mg) led to clinically meaningful improvements in pain and emotional well-being, with the 200 mg group showing up to 169% higher probabilities of achieving these improvements at 6 months, indicating its efficacy in managing endometriosis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life Improvements in Patients With Endometriosis Treated With Elagolix. Taylor, HS., Soliman, AM., Johns, B., et al.[2022]

Citations

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pubmed.ncbi.nlm.nih.gov

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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 ...

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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 ...

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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 ...

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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.

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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.

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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%).

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orilissa.com

orilissa.com/about/side-effects-and-safety-considerations

Understanding Side Effects

The most common serious adverse events reported in the clinical studies included appendicitis (0.3%), abdominal pain (0.2%), and back pain (0.2%). For more ...

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pmc.ncbi.nlm.nih.gov

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

A Clinician's Guide to the Treatment of Endometriosis with ...

Although preclinical data do not suggest that elagolix has teratogenic effects, 2 congenital malformations occurred among the 49 reported pregnancies. Overall, ...

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accessdata.fda.gov/drugsatfda_docs/label/2021/210450s004s005s006lbl.pdf

ORILISSA® (elagolix) tablets, for oral use - accessdata.fda.gov

Among the 2090 subjects exposed to ORILISSA in the endometriosis Phase 2 and Phase 3 studies, there were four reports of suicidal ideation. In addition to the ...

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This is a Phase 3, dose-escalation study designed to evaluate the safety and efficacy of both elagolix alone and elagolix plus estradiol/norethindrone ...