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

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.

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)