A Multi-Center Study To Evaluate Multiple Doses of NT100 Following IVF In Women With Repeated IVF Failures (Thrive-IVF)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety and tolerability of multiple doses of subcutaneous NT100 vs placebo following in vitro fertilization (IVF) in women with a history of repeated IVF failures.

Detailed Description
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NT-03 will be a randomized, double blind, multi-center, placebo controlled study of multiple doses of subcutaneous NT100 following IVF in women with a history of repeated IVF failures. Approximately 150 subjects will be randomized in a 1:1:1 ratio to receive subcutaneous NT100 low dose, NT100 high dose, or placebo, qd for up to 4 weeks. Screening will include a standard IVF stimulation protocol, followed by fertilization and culture of embryos. If the subject remains eligible, she will be randomized to receive study drug. All subjects will be followed for 4 weeks after the last dose of study drug. At Week 10 of gestation, subjects who are pregnant will roll over into a follow-up study (NT-04) to assess subsequent pregnancy, delivery, and neonatal outcomes.

Official Title
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A Randomized, Double Blind, Multi-Center, Placebo Controlled Study To Evaluate The Efficacy, Safety, And Tolerability Of Multiple Doses Of NT100 Following IVF In Women With A History Of Repeated IVF Failures (Thrive-IVF)

Conditions
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Repeated IVF Failure

Intervention / Treatment
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* Drug: NT100
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-menopausal female 21-38 years of age at screening History of repeated IVF failures despite transfer of good-quality embryos, defined as follows: ...1) 3 or more IVF cycles involving transfer of at least two good-quality cleavage-stage embryos or at least one good-quality blastocyst (2010 SART (Society for Assisted Reproductive Technologies) grading criteria)that resulted in one of the following outcomes: * .....a) no pregnancy * .....b) biochemical pregnancy * .....c) spontaneous abortion of an intrauterine clinical pregnancy before or equal to completed Week 8 of gestation ...2) At least two of the eligible IVF failures must have involved transfer of fresh embryos ...3) At least two of the eligible IVF failures must have involved retrieval of at least 5 oocytes ...4) No live birth, abortion later than Week 8 of gestation, or stillbirth may have occurred since the first of these IVF failures Body mass index (BMI) of 19-38 kg per m2 at screening TSH (thyroid-stimulating hormone) less than or equal to 4.0 mIU/L(milli-International units per Liter) for subjects with no history of hypothyroidism, or TSH less than or equal to 2.5 mIU/L for subjects with a history of hypothyroidism, at screening Exclusion Criteria: Prior diagnosis of moderate or severe ovarian hyperstimulation syndrome (OHSS) Clinically confirmed polycystic ovary syndrome (PCOS) History of a major congenital anomaly in the subject, her current male partner, or first degree relative of either the subject or her current male partner Known karyotype abnormalities in either the subject or her current male partner / sperm donor Any prior pregnancy terminated for a fetal medical condition History of severe (stage IV) endometriosis Current or past systemic autoimmune disease Any uncontrolled clinically significant medical condition (e.g. asthma, Type II diabetes, infection)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NT100 Dose 1<br>NT100 Dose 1 | Drug: NT100<br> <br> |
| Experimental: NT100 Dose 2<br>NT100 Dose 2 | Drug: NT100<br> <br> |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing clinical pregnancy rate | The primary efficacy outcome measure is the ongoing clinical pregnancy rate at Week 8 of gestation. | Week 8 of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical evidence of pregnancy rate (as measured by hCG) |  | Week 4 of gestation | 
| Ongoing clinical pregnancy rate |  | Weeks 6 and 10 of gestation | 
| Implantation rate following embryo transfer |  | Week 8 of gestation | 
| Number of subjects with adverse events and serious adverse events |  | through 4 weeks after last dose of study drug (up to Week 10 of gestation) | 
| Changes in clinical laboratory parameters following study drug exposure |  | through 4 weeks after the last dose of study drug (up to Week 10 of gestation) | 
| Moderate to severe ovarian hyperstimulation syndrome (OHSS) rate |  | through Week 10 of gestation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF failure, Repeated IVF failure, Implantation failure, Repeated implantation failure, IVF, NT100