OBE001 Phase 2 Dose-finding Study Versus Placebo in Women Undergoing Embryo Transfer in the Context of IVF-ICSI (IMPLANT)

A Phase 2, Double-blind, Dose-finding, Placebo-controlled Study to Assess the Safety and Efficacy of a Single Oral Administration of OBE001 to Improve Embryo Implantation Following IVF or ICSI

The primary objective of this study is to assess the increase in clinical pregnancy rate after administration of a range of single oral doses of OBE001, an oral oxytocin antagonist, compared to placebo.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Placebo; Drug: OBE001 dose 1; Drug: OBE001 dose 2; Drug: OBE001 dose 3

Detailed Description

The study is a prospective, dose-finding, randomised, parallel group, double-blind, placebo-controlled study investigating the efficacy and the safety of the oxytocin receptor antagonist OBE001 in 240 women undergoing embryo transfer following IVF or ICSI.

The four-arm study (OBE001 dose 1, dose 2, dose 3, and placebo) design will allow evaluation of a possible dose-dependent pattern of action of OBE001 and, simultaneously, comparison of active compound with placebo with regard to both efficacy and safety.

• Study Type: Interventional
• Enrollment (Actual): 247
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
• Czechia
  • Hradev Kralove, Czechia
  • Olomouc, Czechia
  • Prague, Czechia
  • Zlin, Czechia
• Denmark
  • Copenhagen, Denmark
  • Hvidovre, Denmark
• Poland
  • Bialystok, Poland
  • Katowice, Poland
  • Szczecin, Poland
  • Warsaw, Poland
• Spain
  • Alicante, Spain
  • Barakaldo, Spain
  • Barcelona, Spain
  • Bilbao, Spain
  • Sevilla, Spain
  • Vigo, Spain
• United Kingdom
  • London, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 36 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Key Inclusion Criteria

1. Women with medically indicated IVF or ICSI using her own oocytes.
2. GnRH antagonist protocol, a single injection of hCG for triggering final follicular maturation and luteal phase support with vaginal micronized progesterone.
3. Evidence of uterine contractions by transvaginal ultrasound at baseline.

Key Exclusion Criteria

1. Blastocyst stage or frozen-thaw transfers
2. Clinically significant abnormalities in ECG, vital signs, physical examination or clinical laboratory results
3. Severe endometriosis and/or adenomyosis or risk of ovarian hyper stimulation syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo dispersible tablets for single oral administration
Experimental: OBE001 dose 1	Drug: OBE001 dose 1; OBE001 dispersible tablets for single oral administration
Experimental: OBE001 dose 2	Drug: OBE001 dose 2; OBE001 dispersible tablets for single oral administration
Experimental: OBE001 dose 3	Drug: OBE001 dose 3; OBE001 dispersible tablets for single oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFFICACY ENDPOINTS Percentage of women with an intra-uterine pregnancy with positive embryo heart-beat	Percentage of women with an intra-uterine pregnancy with positive embryo heart-beat at about 6 weeks post ET day.	about 6 weeks post ET day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFFICACY ENDPOINTS Percentage of women with positive blood pregnancy test	Percentage of women with positive blood pregnancy test at 14 days post OPU day.	14 days post OPU day
EFFICACY ENDPOINTS Percentage of women with an intra-uterine pregnancy with positive embryo heart-beat	Percentage of women with an intra-uterine pregnancy with positive embryo heart-beat at 10 weeks post OPU day.	10 weeks post OPU day
EFFICACY ENDPOINTS The embryo-implantation rate	The embryo-implantation rate defined as the number of intra-uterine embryos with positive heart-beat at 6 weeks post ET day divided by the number of embryos transferred	6 weeks post ET day
EFFICACY ENDPOINTS Change from baseline to the time of ET in the rate of uterine contractions	Change from baseline to the time of ET in the rate of uterine contractions (UC/min).	at 3.5 hours after dose administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAFETY ENDPOINTS Treatment emergent adverse events frequency and severity	Treatment emergent adverse events frequency and severity	up to 10 weeks post OPU day
SAFETY ENDPOINTS (Haematology and biochemistry assessments)	Haematology and biochemistry assessments at screening and at visit V3 (14 days post OPU day)	14 days post OPU day
PHARMACOKINETIC ENDPOINTS Plasma levels of OBE001	Plasma levels of OBE001	at 3.5 hours after dose administration
PHARMACOKINETIC-PHARMACODYNAMIC ENDPOINTS :Uterine contractions relationship to OBE001 plasma levels and pregnancy rate	Uterine contractions relationship to OBE001 plasma levels and pregnancy rate	up 10 weeks post OPU day

Collaborators and Investigators

• Sponsor: ObsEva SA
• Investigators: Study Director: Clinical Study Director, ObsEva SA

Publications and helpful links

General Publications

• Griesinger G, Blockeel C, Pierzynski P, Tournaye H, Visnova H, Humberstone A, Terrill P, Pohl O, Garner E, Donnez J, Loumaye E. Effect of the oxytocin receptor antagonist nolasiban on pregnancy rates in women undergoing embryo transfer following IVF: analysis of three randomised clinical trials. Hum Reprod. 2021 Mar 18;36(4):1007-1020. doi: 10.1093/humrep/deaa369.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: November 19, 2014
• First Submitted That Met QC Criteria: December 4, 2014
• First Posted (Estimate): December 8, 2014

Study Record Updates

• Last Update Posted (Actual): October 23, 2017
• Last Update Submitted That Met QC Criteria: October 20, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: IVF; ICSI
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: 14-OBE001-013