SIRT-1 Antagonism for Endometrial Receptivity (SAFER)

Wake Forest University (WFU)

Status and phase: Withdrawn; Phase 2

Conditions: Infertility Unexplained; Endometrial Diseases; Endometriosis; Uterine Diseases; Infertility; Female, Nonimplantation

Treatments: Drug: EX-527 (Selisistat); Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04184323

BL5280

Details and patient eligibility

About

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.

Full 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.

Sex: Female

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 2 patient groups, including a placebo group

EX-527

Active Comparator group

Description:

The drug will be administered daily for 5 days beginning with the start of progesterone therapy and ended 24 hours before embryo transfer

Treatment:

Drug: EX-527 (Selisistat)

Placebo

Placebo Comparator group

Description:

The placebo will be administered daily for 5 days beginning with the start of progesterone therapy and ended 24 hours before embryo transfer

Treatment:

Drug: Placebo