EndometriosisPhase 2SAFERNCT04184323
SIRT-1 Antagonism for Endometrial Receptivity
A Phase 2 study testing EX-527 (Selisistat) in people with Endometriosis and Uterine Diseases, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Endometriosis, Uterine Diseases, Endometrial Diseases
- What is being tested?
- EX-527 (Selisistat)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2022to Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- systemic illness affecting kidneys or liver; chronic headache or severe migraine
- Endometritis, hydrosalpinges, and known adenomyosis
- Uterine septum, uterine fibroids, endometrial polyps
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest School of Medicine
Winston-Salem, North Carolina, 27157
About this study
Official title: SIRT1-1 Antagonist Therapy Before Embryo Transfer to Improve Endometrial Receptivity and Life Pregnancy Rates
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.
Read the 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.
- Conditions
- Endometriosis, Uterine Diseases, Endometrial Diseases, Infertility Unexplained, Infertility; Female, Nonimplantation
- Being tested
- EX-527 (Selisistat), Placebo
- Keywords
- endometriosis, SIRT1, Progesterone resistance
- Medical subject headings
- Endometriosis, Uterine Diseases, Infertility, Progesterone Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EX-527 (Selisistat)Drug
Also called SEN0014196
EX-527 is a specific inhibitor of the histone deacetylase Sirtuin-1 (SirT1). It is being given to reverse the effects of endometriosis, namely progesterone resistance, that is thought to interfere with the establishment of pregnancy in women with endometriosis
PlaceboDrug
We will use the same vehicle for producing the active drug such as maltose without any hormones or active components
| Study group | Role | What they receive |
|---|---|---|
| EX-527 | Active comparator | The drug will be administered daily for 5 days beginning with the start of progesterone therapy and ended 24 hours before embryo transfer Receives: Drug: EX-527 (Selisistat) |
| Placebo | Placebo comparator | The placebo will be administered daily for 5 days beginning with the start of progesterone therapy and ended 24 hours before embryo transfer Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth rate
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
Measured: 9 months to 2 years
Secondary outcomes (2)
Pregnancy rate
The number of subjects with a demonstrated pregnancy based on elevated and sustained hCG levels divided by the number of embryo transfers per group
Measured: 9 months to 2 years
Miscarriage rate
The number of sustained pregnancies lost divided by the number of pregnancies in each group
Measured: 9 months to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2019
- Study startJan 2022 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double blind, placebo controlled comparison of SirT1 inhibitor treatment for implantation failure associated with endometriosis
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bruce A Lessey, MD, PhD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04184323
- Sponsor's protocol ID
- BL5280
- Acronym
- SAFER
- Status last verified
- Nov 2020
- First submitted
- 27 Nov 2019
- Last updated
- 17 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The demographic data, group assignment, and outcome data for each subject will be shared with other researchers including embryo grade, stage, pregnancy results (pregnant, not pregnant, miscarriage, ongoing pregnancy, Live birth)
Publications
Westerberg G, Chiesa JA, Andersen CA, Diamanti D, Magnoni L, Pollio G, Darpo B, Zhou M. Safety, pharmacokinetics, pharmacogenomics and QT concentration-effect modelling of the SirT1 inhibitor selisistat in healthy volunteers. Br J Clin Pharmacol. 2015 Mar;79(3):477-91. doi: 10.1111/bcp.12513.
PubMed 25223836Yoo JY, Kim TH, Fazleabas AT, Palomino WA, Ahn SH, Tayade C, Schammel DP, Young SL, Jeong JW, Lessey BA. KRAS Activation and over-expression of SIRT1/BCL6 Contributes to the Pathogenesis of Endometriosis and Progesterone Resistance. Sci Rep. 2017 Jul 28;7(1):6765. doi: 10.1038/s41598-017-04577-w.
PubMed 28754906Likes 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.
PubMed 30610661Almquist 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.
PubMed 29126613
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SIRT1-1 Antagonist Therapy Before Embryo Transfer to Improve Endometrial Receptivity and Life Pregnancy Rates
- ClinicalTrials.gov ID
- NCT04184323
- Acronym / sponsor ID
- SAFER / BL5280
- Conditions
- Endometriosis, Uterine Diseases, Endometrial Diseases, Infertility Unexplained, Infertility; Female, Nonimplantation
- Keywords
- endometriosis, SIRT1, Progesterone resistance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- Jan 2022 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 3 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Double blind, placebo controlled comparison of SirT1 inhibitor treatment for implantation failure associated with endometriosis
| Arm | Type | Receives |
|---|---|---|
| EX-527 | Active comparator | Drug: 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 comparator | Drug: PlaceboThe placebo will be administered daily for 5 days beginning with the start of progesterone therapy and ended 24 hours before embryo transfer |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- systemic illness affecting kidneys or liver; chronic headache or severe migraine
- Endometritis, hydrosalpinges, and known adenomyosis
- Uterine septum, uterine fibroids, endometrial polyps
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EX-527 (Selisistat)Also: SEN0014196EX-527 is a specific inhibitor of the histone deacetylase Sirtuin-1 (SirT1). It is being given to reverse the effects of endometriosis, namely progesterone resistance, that is thought to interfere with the establishment of pregnancy in women with endometriosis | Drug | EX-527 |
| PlaceboWe will use the same vehicle for producing the active drug such as maltose without any hormones or active components | Drug | Placebo |
Primary outcome
Live birth rate
Time frame: 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
2 secondary outcomes
Pregnancy rate
Time frame: 9 months to 2 years
Miscarriage rate
Time frame: 9 months to 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2021.
- Background: PubMed 25223836Westerberg G, Chiesa JA, Andersen CA, Diamanti D, Magnoni L, Pollio G, Darpo B, Zhou M. Safety, pharmacokinetics, pharmacogenomics and QT concentration-effect modelling of the SirT1 inhibitor selisistat in healthy volunteers. Br J Clin Pharmacol. 2015 Mar;79(3):477-91. doi: 10.1111/bcp.12513.
- Background: PubMed 28754906Yoo JY, Kim TH, Fazleabas AT, Palomino WA, Ahn SH, Tayade C, Schammel DP, Young SL, Jeong JW, Lessey BA. KRAS Activation and over-expression of SIRT1/BCL6 Contributes to the Pathogenesis of Endometriosis and Progesterone Resistance. Sci Rep. 2017 Jul 28;7(1):6765. doi: 10.1038/s41598-017-04577-w.
- Background: PubMed 30610661Likes 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.
- Background: PubMed 29126613Almquist 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.
- Individual participant dataSharing planned: Yes. The demographic data, group assignment, and outcome data for each subject will be shared with other researchers including embryo grade, stage, pregnancy results (pregnant, not pregnant, miscarriage, ongoing pregnancy, Live birth)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce A Lessey, MD, PhD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EX-527 (Selisistat) in people with Endometriosis and Uterine Diseases, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth rate (time frame: 9 months to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04184323, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2021.