SIRT-1 Antagonism for Endometrial Receptivity

Phase 2

Withdrawn

• Conditions: Infertility; Female, Nonimplantation; Endometrial Diseases; Infertility Unexplained; Endometriosis; Uterine Diseases
• Interventions: Drug: EX-527 (Selisistat); Drug: Placebo

• Registration Number: NCT04184323
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

Progesterone resistance is mediated through epigenetic modification through SirT1 activation and is thought to contribute to infertility and progression of endometriosis. Endometriosis is a leading cause of unexplained IVF failure secondary to inflammatory changes that induce SirT1. The current study is designed to investigate a small molecule inhibitor of SirT1, in the clinical setting of In Vitro Fertilization and Embryo Transfer. The SAFER trial will compare EX-527 to placebo in a randomized, double-blind trial. Primary endpoints include Live Birth Rate (LBR) and secondary outcomes include pregnancy rate (PR), miscarriage rate (MR) and implantation failure rate.

Detailed Description

The SAFER Trial will enroll women with unexplained failure after embryo transfer with euploid embryos. Subjects must have existing euploid embryos for transfer and test positive for SirT1 testing on endometrial biopsy. To qualify, they must be 18 to 40 years of age, have a normal uterine cavity, no serious systemic diseases (diabetes, lupus, cancer, etc) and be willing to be randomized to treatment with a SirT1 inhibitor, EX-527 or placebo. The medication will be provided and administered for 5 days prior to embryo transfer, after progesterone therapy is begun. The drug will be stopped 24 hr before embryo transfer. Standard protocols will be used including administration of progesterone, checking hCG 8 days after transfer, ultrasound monitoring of pregnancy and pregnancy outcomes recording, with Live Birth Rate (LBR) being the primary outcome of interest. We expect to enroll 30 women, with 15 subjects per arm. The goal of this study is to demonstrate efficacy for a specific inhibitor of SirT1 as a primary treatment of defects in endometrial receptivity due to endometriosis.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2019-11-27
• Study First Submitted QC: 2019-12-02
• Study First Posted: 2019-12-03
• Status Verified: 2020-11
• Last Update Submitted: 2021-11-08
• Last Update Posted: 2021-11-17
• Study Start: 2022-01
• Primary Completion: 2023-12
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

• Must test positive for SIRT1 on mid-luteal endometrial biopsy
• Prior failed embryo transfer with euploid embryos
• Have at least one euploid embryo for transfer

Read More

Exclusion Criteria

• systemic illness affecting kidneys or liver; chronic headache or severe migraine
• Endometritis, hydrosalpinges, and known adenomyosis
• Uterine septum, uterine fibroids, endometrial polyps

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EX-527	EX-527 (Selisistat)	The drug will be administered daily for 5 days beginning with the start of progesterone therapy and ended 24 hours before embryo transfer
Placebo	Placebo	The placebo will be administered daily for 5 days beginning with the start of progesterone therapy and ended 24 hours before embryo transfer

Primary Outcome Measures

Name	Time	Method
Live birth rate	9 months to 2 years	The number of successful pregnancies ending in live birth at the conclusion of the study divided by the number of embryo transfers in each group

Secondary Outcome Measures

Name	Time	Method
Miscarriage rate	9 months to 2 years	The number of sustained pregnancies lost divided by the number of pregnancies in each group
Pregnancy rate	9 months to 2 years	The number of subjects with a demonstrated pregnancy based on elevated and sustained hCG levels divided by the number of embryo transfers per group

Trial Locations

Locations (1)

Wake Forest School of Medicine; 🇺🇸 Winston-Salem, North Carolina, United States