Phase 3 Placebo Controlled Study of Nolasiban to Improve Pregnancy Rates in Women Undergoing IVF/ICSI (IMPLANT2)

A Phase 3, Double-blind, Randomized, Placebo-controlled Study to Assess the Efficacy and Safety of a Single Oral Administration of Nolasiban to Improve Pregnancy Rates Following IVF or ICSI in Day 3 and Day 5 Fresh Embryo Transfer Cycles

The primary objective of this study is to confirm the efficacy of a single oral 900mg dose of nolasiban to increase the ongoing clinical pregnancy rate at 10 weeks post embryo transfer (ET) day.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Nolasiban 900mg; Drug: Placebo

Detailed Description

The study is a prospective, randomized, parallel group, double-blind, placebo-controlled study to confirm the efficacy and the safety of the oxytocin receptor antagonist, nolasiban, in 760 women undergoing fresh embryo transfer following in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI).

• Study Type: Interventional
• Enrollment (Actual): 810
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Investigator ID 1001
  • Brussels, Belgium
    • Investigator ID 1002
  • Brussels, Belgium
    • Investigator ID 1003
  • Brussels, Belgium
    • Investigator ID 1004
• Czechia
  • Olomouc, Czechia
    • Investigator ID 1107
  • Prague, Czechia
    • Investigator ID 1101
  • Prague, Czechia
    • Investigator ID 1102
  • Prague, Czechia
    • Investigator ID 1103
  • Prague, Czechia
    • Investigator ID 1104
  • Prague, Czechia
    • Investigator ID 1108
  • Teplice, Czechia
    • Investigator ID 1109
  • Zlin, Czechia
    • Investigator ID 1106
• Denmark
  • Copenhagen, Denmark
    • Investigator ID 1204
  • Herlev, Denmark
    • Investigator ID 1205
  • Hvidovre, Denmark
    • Investigator ID 1202
  • Skive, Denmark
    • Investigator ID 1203
• Estonia
  • Tartu, Estonia
    • Investigator ID 1301
  • Tartu, Estonia
    • Investigator ID 1303
• Finland
  • Helsinki, Finland
    • Investigator ID 1401
  • Helsinki, Finland
    • Investigator ID 1402
  • Oulu, Finland
    • Investigator ID 1403
• Germany
  • Heidelberg, Germany
    • Investigator ID 1501
  • Lübeck, Germany
    • Investigator ID 1502
  • Mainz, Germany
    • Investigator ID 1504
  • Marburg, Germany
    • Investigator ID 1503
• Hungary
  • Budapest, Hungary
    • Investigator ID 1601
  • Budapest, Hungary
    • Investigator ID 1604
  • Pécs, Hungary
    • Investigator ID 1603
  • Tapolca, Hungary
    • Investigator ID 1602
• Poland
  • Białystok, Poland
    • Investigator ID 1701
  • Białystok, Poland
    • Investigator ID 1703
  • Białystok, Poland
    • Investigator ID 1705
  • Katowice, Poland
    • Investigator ID 1702
  • Szczecin, Poland
    • Investigator ID 1704
  • Warsaw, Poland
    • Investigator ID 1706
• Spain
  • Barakaldo, Spain
    • Investigator ID 1801
  • Barcelona, Spain
    • Investigator ID 1805
  • Barcelona, Spain
    • Investigator ID 1808
  • Leioa, Spain
    • Investigator ID 1809
  • Madrid, Spain
    • Investigator ID 1804
  • Madrid, Spain
    • Investigator ID 1807
  • Sevilla, Spain
    • Investigator ID 1811
  • Valencia, Spain
    • Investigator ID 1806

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:

• Indicated for IVF/ICSI in the context of assisted reproductive technology (ART)
• Follow a gonadotropin releasing hormone (GnRH) antagonist protocol, single injection of human chorionic gonadotropin (hCG) for triggering final follicular maturation and luteal phase support with vaginal micronized progesterone.
• Single, fresh D3 or D5 embryo transfer

Key Exclusion Criteria:

• Frozen-thawed embryo transfer
• More than 20 oocytes in the current controlled ovarian hyperstimulation (COH) cycle
• Serum P4 greater than 1.5 ng/mL on the day of hCG administration

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo dispersible tablets for single oral administration
Experimental: Nolasiban 900 mg	Drug: Nolasiban 900mg; Nolasiban dispersible tablets for single oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-uterine pregnancy with fetal heart beat at 10 weeks	Intra-uterine pregnancy with fetal heart beat at 10 weeks post embryo transfer day	10 weeks post ET day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth	Live birth after 24 weeks of gestation	Up to 42 weeks of gestation
Miscarriage	Any clinical pregnancy that does not result in a live birth prior 24 weeks	From 6 weeks post ET to 24 weeks gestation
Intra-uterine pregnancy at 6 weeks	Intra-uterine pregnancy with fetal heart beat at 6 weeks post ET day	6 weeks post ET
Positive blood pregnancy test	Positive blood pregnancy test at 14 days post oocyte pick-up (OPU)	14 days post OPU

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Frequency and severity of treatment emergent adverse events	Through study completion, up to 11 months
Neonatal assessments	Incidence of any malformation or any significant morbidity during the neonatal period	Birth of infant until 28 days
ASQ-3	Ages and Stages Questionnaire-3 (ASQ-3) domain score(s) at 6 months, adjusted for gestational age at birth	6 months after term

Collaborators and Investigators

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

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 (Actual): March 6, 2017
• Primary Completion (Actual): March 21, 2018
• Study Completion (Actual): February 19, 2019

Study Registration Dates

• First Submitted: March 6, 2017
• First Submitted That Met QC Criteria: March 9, 2017
• First Posted (Actual): March 16, 2017

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: IVF; ICSI
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: 16-OBE001-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No