Elagolix for Fertility Enhancement Clinical Trial

Endometriosis Clinical Trial

— EFFECT  

Official title:

Elagolix for Fertility Enhancement Clinical Trial (EFFECT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04039204
• Other study ID #: IRB00059474
• Status: Completed
• Phase: Phase 2
• Start date: January 15, 2022
• Est. completion date: August 9, 2023

Study information

• Verified date: December 2023
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Studies suggest that undiagnosed endometriosis results in poor reproductive outcomes in the setting of In Vitro Fertilization and Embryo Transfer (IVF-ET). Biomarkers that predict endometriosis including B-cell lymphoma (BCL6) and Sirtuin 1 (SIRT1) are associated with reduced pregnancy rates following IVF-ET. Treatment with gonadotropin releasing hormone (GnRHr) receptor agonists (leuprolide acetate depot) has been shown to improve pregnancy rates following embryo transfer (ET). In this randomized controlled trial, a new generation GnRHr antagonist, elagolix, will be compared to oral contraceptives (OCPs) for suppression of suspected endometriosis prior to ET. Both groups will receive two months of treatment prior to frozen embryo transfer of a single euploid embryo. Outcomes will include pregnancy rate, miscarriage rate and ongoing and live birth rate following treatment. Patients experiencing unanticipated problems or who experience adverse events such that they do not tolerate the treatment they are assigned, will be allowed to discontinue treatment and be provided the opportunity to use the other treatment if they so choose. The outcomes of such cycles would be collected separately and included as observational data only and not included in the randomized data analysis. Alternatively, they can simply drop out of the study and resume medical therapy as appropriate or pursue frozen embryo transfer as previously planned.

Description:

Although meta-analyses have not demonstrated an effect of endometriosis on IVF outcomes, most women with endometriosis undergoing IVF have not been diagnosed or treated for their disease. Recent evidence suggests that biomarkers for endometriosis predict IVF failure and miscarriage. Further suppression of endometriosis prior to IVF has been shown to dramatically improve pregnancy rates in unexplained infertility with suspected endometriosis. Elagolix (Orilissa) is a new generation FDA approved orally active GnRHr antagonist that is rapidly reversible, for the treatment of endometriosis and pelvic pain. There have been no studies on the efficacy of elagolix for the treatment of endometriosis-associated infertility. Given the recent study in Fertility and Sterility demonstrating IVF outcome prediction using BCL6 as a biomarker for the presence of endometriosis and subsequent preliminary data showing benefit using surgery and GnRH agonist therapy, there is adequate rationale to examine the use of the orally active, non-peptide compound (elagolix) for estrogen suppression prior to frozen embryo transfer in women who test positive for BCL6 and an associated protein, SIRT1. In this multi-central randomized controlled trial (RCT), the EFFECT Trial, the investigators plan to recruit 100 subjects with prior unexplained IVF failure with positive endometrial BCL6/SIRT1 expression. To qualify all subjects will need to have a preimplantation genetic testing (PGT-A) tested euploid embryo and intentions to undergo frozen embryo transfer. Subjects will be randomized to receive elagolix (200 mg BID) or OCPs for 2 months prior to standardized FET. Primary study outcomes will be pregnancy outcome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: August 9, 2023
• Est. primary completion date: August 9, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

Inclusion Criteria:

• Anti-Mullerian Hormone (AMH) > 0.5 and < 10
• At least 1 euploid embryo for transfer
• Prior endometrial biopsy showing elevated BCL6 and SIRT1 expression
• Endometrial thickness > 5.9 and < 14 mm

Exclusion Criteria:

• Uterine fibroids > 4 cm (intramural)
• Polycystic ovary syndrome (Rotterdam criteria)
• Ovarian failure and donor eggs or oocytes
• Positive lupus anticoagulant or positive anti-cardiolipin antibody testing
• Diabetes mellitus (Type I or II)
• Untreated hypothyroidism
• Untreated hyperprolactinemia
• BMI <17 or > 35
• Uncorrected uterine anomaly

Related Conditions & MeSH terms

• Endometriosis
• Infertility
• Unexplained Infertility

Intervention

Drug:
• Elagolix
This orally active, reversible GnRH antagonist will be used to suppress endometriosis by lowering estrogen levels for 2 months prior to FET
• Oral Contraceptive
Oral contraceptive prescribed by physician.

Locations

Country	Name	City	State
United States	Wake Forest Univesity Health Sciences	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	Stanford University, University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

References & Publications (5)

Almquist LD, Likes CE, Stone B, Brown KR, Savaris R, Forstein DA, Miller PB, Lessey BA. Endometrial BCL6 testing for the prediction of in vitro fertilization outcomes: a cohort study. Fertil Steril. 2017 Dec;108(6):1063-1069. doi: 10.1016/j.fertnstert.2017.09.017. Epub 2017 Nov 7. — View Citation

Likes CE, Cooper LJ, Efird J, Forstein DA, Miller PB, Savaris R, Lessey BA. Medical or surgical treatment before embryo transfer improves outcomes in women with abnormal endometrial BCL6 expression. J Assist Reprod Genet. 2019 Mar;36(3):483-490. doi: 10.1007/s10815-018-1388-x. Epub 2019 Jan 4. — View Citation

Littman E, Giudice L, Lathi R, Berker B, Milki A, Nezhat C. Role of laparoscopic treatment of endometriosis in patients with failed in vitro fertilization cycles. Fertil Steril. 2005 Dec;84(6):1574-8. doi: 10.1016/j.fertnstert.2005.02.059. — View Citation

Surrey E, Taylor HS, Giudice L, Lessey BA, Abrao MS, Archer DF, Diamond MP, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Singh SS, Rechberger T, Agarwal SK, Duan WR, Schwefel B, Thomas JW, Peloso PM, Ng J, Soliman AM, Chwalisz K. Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies. Obstet Gynecol. 2018 Jul;132(1):147-160. doi: 10.1097/AOG.0000000000002675. Erratum In: Obstet Gynecol. 2018 Dec;132(6):1507-1508. — View Citation

Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, Surrey E, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Rowan JP, Duan WR, Ng J, Schwefel B, Thomas JW, Jain RI, Chwalisz K. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. N Engl J Med. 2017 Jul 6;377(1):28-40. doi: 10.1056/NEJMoa1700089. Epub 2017 May 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ongoing pregnancy rate	The number of viable pregnancies divided by number of frozen embryo transfers	12 to 15 weeks
Primary	Live birth rate	The number of live births divided by number of transfers	9 months
Primary	Number of subjects with categorical outcome of cancellation	based on ultrasound	1 year
Primary	Number of subjects with categorical outcome of not pregnant	based on ultrasound	1 year
Primary	Number of subjects with categorical outcome of biochemical pregnancy	based on ultrasound	1 year
Primary	Number of amniotic sacs	(0, 1, 2, 3) based on ultrasound	1 year
Secondary	Miscarriage rate	The number of subjects with a first trimester pregnancy loss divided by the number of pregnancies	15 week