Embryo implantation in women undergoing embyo transfer following IVF/ICSI in the context of Assisted Reproductive Technology (ART). MedDRA version: 17.0 Level: LLT Classification code 10073184 Term: Embryo transfer System Organ Class: 100000004865
Conditions
Interventions
Product Name: OBE001
Product Code: OBE001
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: NA
CAS Number: 1477482-19-1
Current Sponsor code: OBE001
Other descriptive name: OBE001
Concentra
Sponsors
ObsEva SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The Subject must provide written informed consent prior to initiation of any study related procedures, as shown by a signature on the volunteer consent form. 2. The Subject must be a healthy female volunteer aged from 18 years to 36 years inclusive at screening. 3. The Subject must be medically indicated for IVF/ICSI in the context of ART. 4. The Subject must have undergone not more than 1 previous IVF or ICSI cycle that resulted in a negative ßhCG test, despite transfer of at least one embryo/blastocyst of good quality during the cycle (but not counting any attempts before a prior pregnancy). 5. The Subject must in the current COH cycle for IVF/ICSI follow a GnRH antagonist protocol with or without pre-treatment with an oral contraceptive pill. 6. The Subject must in the current COH cycle for IVF/ICSI receive a single injection of hCG for triggering final follicular maturation. 7. The Subject must in the current COH cycle for IVF/ICSI receive a luteal phase support with vaginal micronized progesterone at 600 mg per day (3 × 200 mg) beginning either on the day of oocyte retrieval or on the day after oocyte retrieval. 8. The Subject must undergo oocyte retrieval for IVF/ICSI for the purpose of fresh transfer on day 3 post-Oocyte Pick-Up day (OPU day + 3 days). 9. The Subject must have had at least 4 mature oocytes picked-up in the preceding COH cycle, if any. 10. The Subject must have at least 4 mature oocytes picked-up in the current COH cycle. 11. The Subject must have at least one good quality embryo in the current COH cycle being defined as having six to eight blastomeres of uniform size and shape at Day 3, ooplasm having no granularity, absence of multinucleation and a maximum fragmentation of 10%. 12. The Subject must present evidence of uterine contractions on transvaginal ultrasound video at baseline (prior to OBE001/placebo administration). 13. The Subject must have at least 1 functional ovary. 14. The Subject must have a BMI = 18 kg/m2 and = 35 kg/m2. 15. The Subject must be able to communicate well with the investigator and research staff and to comply with the requirements of the study protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 240 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. The Subject is programmed for a transfer of 3 or more embryos in the current COH cycle. 2. The Subject is programmed for a blastocyst stage transfer in the current COH cycle. 3. The Subject undergo a frozen-thaw embryo transfer in the current COH cycle. 4. The Subject’s partner is requiring a surgical testicular sperm extraction. 5. The Subject has a known abnormal karyotype. 6. The Subject has a known acquired or congenital thrombophilia disease. 7. The Subject has any condition, including findings in the medical history or in the pre-trial assessments, which in the opinion of the PI constitutes a risk or a contraindication for the participation of the subject in the trial or that could interfere with the trial objectives, conduct or evaluation. 8. The Subject has any clinically significant abnormality in the results of the screening safety laboratory tests, including AST, ALT, GGT, alkaline phosphatase or total bilirubin above twice upper limit of normal. In case of isolated GGT increase, a single re-test is allowed. 9. The Subject has any significant abnormality relevant to the ART procedure and outcome, in the results of the screening gynaecological examination, which in the opinion of the PI could interfere with the trial objectives, conduct or evaluation (e.g. significant uterine anomaly or hydrosalpinges documented during screening ultrasound). 10. The Subject has a known severe endometriosis (stage III or IV) and/or adenomyosis. 11. The Subject is at risk of severe Ovarian Hyper Stimulation Syndrome (OHSS). 12. The Subject has any clinically significant abnormality on the 12-lead ECG recording at screening. 13. The Subject has any clinically significant abnormality on arterial blood pressure (BP) or heart rate (HR) at screening. 14. The Subject has a known positive results from virology tests for hepatitis B surface antigen (HBsAg) (not due to vaccination), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) 1 or 2. 15. The Subject is prone to frequent, severe hypersensitivity to drugs, in particular with chemical structure similar to OBE001. 16. The Subject has been administered with any experimental drug in the 12 weeks before dosing. 17. The Subject has forfeit her freedom by administrative or legal award or who was under guardianship. 18. The Subject is likely to require treatment with drugs that are not permitted during the study from the day of hCG single injection up to the study visit V3 (OPU day + 14 days) such as: • Drugs with utero-relaxant properties: Ca channel blockers, beta-sympathomimetic agents, nitroglycerine, magnesium sulfate (MgSO4), potassium channel openers, NSAIDs, drugs for functional GI disorders • Drugs with utero-tonic properties: Dopamine, progesterone antagonists, prostaglandin analogues • triptins and ergotamines 19. The Subject has a history of, or known current (within twelve months) problems with alcohol or drug abuse. 20. The Subject has participated in any previous studies involving oxytocin receptor antagonists during this and any previous ART cycles.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy objective: • To assess the efficacy of a range of single oral doses of OBE001 compared to placebo to increase the clinical pregnancy rate defined as a positive embryo heart-beat at 5 weeks post Oocyte Pick-Up (OPU) day. Safety Objective: • To evaluate the safety and tolerability of OBE001 when administered orally to women undergoing embryo transfer following IVF or ICSI. Pharmacokinetic- Pharmacodynamic Objective: • To establish the possible relationship between inhibition of uterine contractions and OBE001 plasma levels.;Secondary Objective: Efficacy Objectives: • To assess the efficacy of a range of single oral doses of OBE001 compared to placebo on the following: - to increase the pregnancy rate defined as a positive blood pregnancy test at 14 days post OPU day. - to increase the on-going pregnancy rate defined as a positive embryo heart-beat at 10 weeks post OPU day. - to increase the embryo-implantation rate defined as the number of intra-uterine embryos with positive heart-beat at 5 weeks post OPU day divided by the number of embryos transferred. - to decrease the rate of uterine contractions (UC/min) prior to embryo transfer. ;Primary end point(s): Efficacy endpoint: • Percentage of women with an intra-uterine pregnancy with positive embryo heart-beat at 5 weeks post OPU day. Safety endpoints: • Treatment emergent adverse events frequency and severity (until the End-of-Study visit). • Haematology and biochemistry assessments at screening (prior to OBE001/placebo administration) and at visit V3 (14 days post OPU day). Pharmacokinetic-Pharmacodynamic endpoints: • Plasma levels of OBE001 (pre-dose and at the time of embryo transfer). • Uterine contractions relationship to OBE001 plasma levels, with possible covariates of serum E2 and P4 levels and uterine contractions at baseline.;Timepoint(s) of evaluation of this end point: - Interim analysis will be performed when 120 randomised subjects will have either completed the study visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: • Percentage of women with positive blood pregnancy test at 14 days post OPU day. • Percentage of women with an intra-uterine pregnancy with positive embryo heart-beat at 10 weeks post OPU day. • The embryo-implantation rate defined as the number of intra-uterine embryos with positive heart-beat at 5 weeks post OPU day divided by the number of embryos transferred. • Change (absolute and relative) from baseline (prior to OBE001/placebo administration) to the time of ET (about 3.5 hours after OBE001/placebo administration and prior to ET) in the rate of uterine contractions (UC/min). ;Timepoint(s) of evaluation of this end point: - Interim analysis will be performed when 120 randomised subjects will have either completed the study visit V4 and/or have terminated the study and/or have been early withdrawn. - At the end of the study | — |
Countries
Belgium, Czech Republic, Denmark, Poland, Spain, United Kingdom
Contacts
Public ContactVéronique Lecomte
ObsEva SA
Outcome results
None listed