Elagolix for Endometriosis

Recruiting at 1 trial location

Overseen By Nina Stachenfeld, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Yale University

Disqualifiers: Smoking, Diabetes, Sleep apnea, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests treatments for endometriosis, a condition where tissue similar to the uterine lining grows outside the uterus, causing pain and other issues. Researchers aim to determine if lowering estrogen levels can help manage the condition and improve blood vessel function. Participants will receive either Elagolix, which lowers estrogen levels, or Ganirelix Acetate, which blocks certain hormones. The trial includes women with endometriosis and a control group of healthy women with regular menstrual cycles. Women who have experienced cyclic pelvic pain or have been diagnosed with endometriosis through surgery might be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

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

Research shows that Elagolix is generally safe, though it can cause some side effects. Serious issues like appendicitis, stomach pain, and back pain occurred in very few cases (0.3% or less). Other side effects included nausea, anxiety, and headaches. Despite these, Elagolix is considered safe for use. The FDA has approved it for treating endometriosis, indicating it is usually well-tolerated.

For Ganirelix Acetate, studies indicate it is safe and well-tolerated, with no new safety concerns found in everyday use. It aids in ovarian stimulation in women, suggesting a good safety record.

Overall, previous studies have shown both treatments to be safe, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Elagolix is unique because it targets endometriosis by directly inhibiting gonadotropin-releasing hormone (GnRH), which reduces estrogen production and alleviates symptoms. Unlike typical treatments like hormonal contraceptives or GnRH agonists, Elagolix offers a non-invasive oral option with a faster onset of action and potentially fewer side effects. Researchers are excited about Ganirelix Acetate as it acts as a GnRH antagonist, potentially providing a more immediate reduction in symptoms compared to traditional therapies. This combination of treatments offers promising alternatives that could improve quality of life for those with endometriosis.

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

Research has shown that Elagolix, a treatment under study in this trial, effectively reduces pain from endometriosis. Studies have found it can decrease painful periods by up to 75% and lessen other pelvic pain by 50-60%. This treatment lowers estrogen levels, which helps reduce pain. Real-world evidence supports these findings, showing significant pain relief after six months of use. While Ganirelix Acetate is also being tested in this trial, Elagolix has a proven track record of reducing pain related to endometriosis. ^{2 4 6 7 8}

Who Is on the Research Team?

Nina Stachenfeld, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for young women aged 18-45, both healthy and those with endometriosis. It's not open to women who have diabetes, severe acute pain from endometriosis needing immediate treatment, high blood pressure (BP>140/90), sleep apnea, or those who smoke.

Inclusion Criteria

I am a woman aged between 18 and 45.

I am a woman aged 18-45 with endometriosis.

Exclusion Criteria

You are a smoker.

I have diabetes.

I do not have severe acute pain from endometriosis needing immediate treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive estrogen suppression treatment to assess its impact on endothelial dysfunction and cardiovascular risk

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Elagolix
• Ganirelix Acetate

Trial Overview The study is testing Elagolix to see if reducing estrogen levels affects the health of blood vessels in women with endometriosis. The idea is that less estrogen might lead to worse vessel function.

How Is the Trial Designed?

Group I: patients with endometriosis Experimental Treatment 1 Intervention

Endometriosis will be diagnosed by history of the disease seen at the time of prior surgery or will be diagnosed by classic clinical symptoms of the disease (cyclic progressive pelvic pain) using prior surgical report reviewed by Dr. Taylor.

Group II: patients without endometriosis Active Control 1 Intervention

Control subjects will be healthy women, with regular menses every 26-34 days. Subjects will be excluded if they have any symptoms of endometriosis, including severe dysmenorrhea or progressive cyclic pelvic pain or prior surgery showing evidence of endometriosis

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+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

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]

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]

In a phase III trial involving 860 women, elagolix, an oral GnRH antagonist, significantly reduced fatigue levels in women suffering from moderate to severe endometriosis-associated pain, with notable improvements observed at 6 months.

Women taking elagolix at 200 mg twice daily experienced the greatest reduction in fatigue, with a significant decrease in fatigue T-scores compared to those on placebo, highlighting its efficacy in managing fatigue related to endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of elagolix treatment on fatigue experienced by women with moderate to severe pain associated with endometriosis. Surrey, ES., Soliman, AM., Agarwal, SK., et al.[2019]

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 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]

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]

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. 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.

8. icer.org icer.org/news-insights/press-releases/elagolix-final-report/

Institute for Clinical and Economic Review Final Report ... Elagolix has known short-term side effects and no long-term comparative safety and efficacy data in relation to several other well-established treatment options ...