Pre-IVF Treatment With a GnRH Antagonist in Women With Endometriosis

NCT04173169 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: 20000271211R01HD100336-01
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 5

Brief Summary

A Phase 3 clinical trial of oral GnRH antagonist pre-treatment for women with endometriosis who are undergoing IVF, with a primary outcome of live birth rate. The investigators' central hypothesis is that in infertile woman with endometriosis undergoing in vitro fertilization-embryo transfer (IVF-ET), live birth rates will improve in those pretreated with GnRH antagonist compared to those not pretreated with GnRH antagonist.

Conditions

Infertility; Endometriosis

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  Live birth rate per participant is defined as live birth at ≥24 weeks of gestation.

  Up to 15 months

Secondary Outcomes (9)

• Fertilization rate

  Up to 9 months

• Number of embryos transferred

  Up to 9 months

• Implantation rate

  Up to 9 months

• Biochemical pregnancy rate

  Up to 9 months

• Clinical pregnancy rate

  Up to 10 months

Study Arms (2)

Pre-IVF Treatment with 60 day course of oral GnRH antagonist

ACTIVE COMPARATOR

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.

Drug: Elagolix 200 MG

Pre-IVF Treatment with 60 day course of Placebo or SOC IVF

OTHER

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.

Other: Placebo or SOC IVF

Interventions

Elagolix 200 MG DRUG

Elagolix tablet

Also known as: Orlissa

Pre-IVF Treatment with 60 day course of oral GnRH antagonist

Placebo or SOC IVF OTHER

Sugar pill manufactured to mimic Elagolix 200mg

Pre-IVF Treatment with 60 day course of Placebo or SOC IVF

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women who plan to undergo IVF for treatment of infertility.
• Age ≥18 and \<40 years at time of egg retrieval or signing informed consent.
• Documentation of diagnosis of endometriosis by surgical visualization of endometriosis (laparoscopy or laparotomy) or diagnosis by pathology within the last 10 years before the initial trial entry visit or documentation of ovarian endometrioma \>2 cm or two or more smaller endometriomas that total \>2 cm in diameter. If entry is based on the presence of an endometrioma, transvaginal ultrasound evaluation must document the same unambiguous endometrioma on two separate occasions in more than one menstrual cycle. Images will be printed or transmitted electronically and read centrally by investigators at Yale to assure uniform diagnostic criteria (classic ground glass appearance) are applied.
• Body mass index (BMI) of 18-40 kg/m2 (both inclusive) at screening.
• AMH \> 0.5ng/ml, within 12 months of a fresh IVF cycle start. For frozen embryo transfers (FET) , AMH level eligibility criteria may not be met as long as the patient has at least one good quality blastocyst stored for the FET.
• Presence of at least one ovary with no clinically significant abnormalities other than endometrioma. For eligible women with evidence of a hemorrhagic ovarian cyst, a repeat US will be needed in a subsequent menstrual cycle to ensure persistent cyst for patient to be deemed eligible.
• Negative urine or cervical swab for gonorrhea and chlamydia within 12 months of screening.
• Willing and able to comply with trial procedures, including reporting of obstetrical outcomes after delivery.

You may not qualify if:

• Use of depot GnRH agonists within 6 months of study start. Use of subcutaneous antagonists or nasal agonist within 2 months of study start unless part of regular IVF or previous IUI cycle°.
• Use of depot medroxyprogesterone acetate (MPA) (injectable) or birth control implants (e.g., Implanon® or Nexplanon®) within 6 months of study start°.
• Continuous use of oral progestins (MPA, NETA) within 1 month of study start°.
• Use of aromatase inhibitors, danazol or hormonal contraceptives (Including combined oral contraceptive pill, progestin-only pill, transdermal patch or contraceptive ring, or double barrier contraception) within 1 month of study start.
• Pregnancy greater than 8 weeks in length within the last 6 months.
• Number of previous IVF/ICSI attempts ≥3 unsuccessful (negative pregnancy test).
• Presence of hydrosalpinx measuring \>2cm on ultrasound, untreated endometrial polyps or intrauterine adhesions.
• Abnormal cytology on a cervical screening based on the American College of Obstetricians and Gynecologists (ACOG) guidelines and patient age. (CIN1 or HPV allowed to participate in the study, CIN2 excluded unless treated and cleared, CIN3 excluded).
• History of malignancy within 5 years of the start of screening, except for treated basal cell carcinoma and squamous cell carcinoma of the skin.
• Any thoughts of suicide in the last 12 months per self-report, or documented in the electronic medical record (EMR).
• Hypersensitivity to the study drugs.
• Planned surgical treatment of endometriosis or planned surgery in the abdominal-pelvic area within the duration of the trial.
• Untreated abnormal prolactin or TSH
• Any conditions that preclude pregnancy.
• Patients with a known history of a low-trauma fracture or other risk factors for osteoporosis or bone loss.

Sponsors & Collaborators

• Yale University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• University of Colorado, Denver: collaborator
• Northwestern University: collaborator
• University of North Carolina: collaborator

Study Sites (5)

University of Colorado Department of Obstetrics & Gynecology

Aurora, Colorado, 80045, United States

Location

Yale School of Medicine Dept.of Ob/Gyn & Reproductive Sciences

New Haven, Connecticut, 06520, United States

Location

Northwestern University Department of Obstetrics and Gynecology

Chicago, Illinois, 60611, United States

Location

Johns Hopkins, Division of Reproductive Science and Women's Health Research

Baltimore, Maryland, 21205, United States

Location

Duke Fertility

Morrisville, North Carolina, 27560, United States

Location

Related Publications (2)

• Taylor H, Li HJ, Carson S, Flores V, Pal L, Robbins J, Santoro NF, Segars JH, Seifer D, Huang H, Young S, Zhang H. Pre-IVF treatment with a GnRH antagonist in women with endometriosis (PREGNANT): study protocol for a prospective, double-blind, placebo-controlled trial. BMJ Open. 2022 Jun 17;12(6):e052043. doi: 10.1136/bmjopen-2021-052043.

  PMID: 35715184 DERIVED

• Pretzel S, Kuhn K, Pal L, Polotsky A, Taylor HS, Zhang H, Robins J, Young SL, Santoro N. Willingness of Women with Endometriosis Planning to Undergo IVF to Participate in a Randomized Clinical Trial and the Effects of the COVID-19 Pandemic on Potential Participation. Reprod Sci. 2022 Feb;29(2):620-626. doi: 10.1007/s43032-021-00705-0. Epub 2021 Aug 6.

  PMID: 34363198 DERIVED

MeSH Terms

Conditions

Infertility; Endometriosis

Interventions

elagolix

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Study Officials

• David Weinberg, PhD

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

  STUDY DIRECTOR

• Hugh Taylor, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Heping Zhang, PhD

  Yale University

  STUDY DIRECTOR

• Nanette Santoro, MD

  University of Colorado, Denver

  STUDY DIRECTOR

• Emily Jungheim, MD

  Northwestern University

  STUDY DIRECTOR

• Steven Young, MD, PhD

  Duke University

  STUDY DIRECTOR

• Abisola Tepede, PharmD

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: For participants who agree to be randomized, a computer-generated randomization list will be created by the PREGnant Data Coordinating Center (DCC) and randomization will be performed prior to the first dose of elagolix. Randomization will have random sizes (2, 4, or 6) of blocks and be stratified by site, i.e. whole blocks are assigned to sites. The randomization list will not be available to any person involved in the conduct and evaluation of the trial until the trial is complete and database is declared clean and is released by the DCC. Likewise, treatment allocation information will not be accessible to investigators (except for serious safety concerns), trial staff at the site or central laboratory personnel during the trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Half of the subjects (200, randomized or not randomized) will receive elagolix 200mg twice a day (BID) and the other half of subjects will receive placebo BID or SOC IVF (200, placebo or SOC IVF). Elagolix or placebo will be taken for a minimum of 60 days before IVF cycle start. For convenience of IVF cycle scheduling, participants may receive up to an additional 14 days of intervention (elagolix or placebo) beyond the minimum 60 days of pre-IVF treatment, such that the last dose of study intervention (elagolix or placebo) is received no more than 24 hours before start of IVF treatment protocol.

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: November 21, 2019
• Study Start: March 15, 2022
• Primary Completion: May 2, 2025
• Study Completion: May 2, 2025
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

US (5)