A Phase 2 Study of OBE001 Versus Placebo in the Delay of Preterm Birth (TERM)

A Phase 2, Double-blind, Parallel Group, Randomised, Placebo Controlled, Proof of Concept Study to Assess the Safety and Efficacy of OBE001 After Oral Administration in Pregnant Women With Threatened Preterm Labour.

The primary objective of this study is to assess the efficacy of a single dose of OBE001, an oral oxytocin antagonist, given for up to 7 days to delay preterm birth by 7 days compared to placebo.

Study Overview

• Status: Terminated
• Conditions: Preterm Labor
• Intervention / Treatment: Drug: OBE001; Drug: Placebo

Detailed Description

The study will be a multi-centre, randomised, parallel group, double-blind, placebo-controlled study in pregnant women with threatened preterm labour between 34^0/7 and 35^6/7 weeks of gestation.

The study will be in 2 parts as follows:

• from screening until the day of delivery (including a treatment period up to seven days)
• a maternal and neonatal follow-up period from the day of delivery until 28 days post expected term date (or until 28 days post-delivery should this be later).

In addition, there will be an observational, safety follow-up of the infants for 2 years to evaluate developmental outcome.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
  • Leuven, Belgium
  • Liege, Belgium
• Germany
  • Bayreuth, Germany
  • Dusseldorf, Germany
  • Tuebingen, Germany
  • Ulm, Germany
• Poland
  • Bialystok, Poland
  • Chorzow, Poland
  • Lodz, Poland
  • Ruda Slaska, Poland
  • Warsaw, Poland
• Spain
  • Barcelona, Spain
  • El Palmar, Spain
  • Madrid, Spain
  • Vitoria - Gasteiz, Spain
  • Zaragoza, Spain
• Switzerland
  • Basel, Switzerland
  • Bern, Switzerland
  • Geneva, Switzerland
  • Lausanne, Switzerland
• United Kingdom
  • Leeds, United Kingdom
  • London, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Gestational age (GA) between 34^0/7 and 35^6/7 weeks.
• Subjects with symptoms of preterm labour.
• Subjects with a singleton pregnancy.

Exclusion Criteria:

• Foetal death in utero in current pregnancy or in previous pregnancy after gestational week 24 or expected high risk of foetal death in the current pregnancy.
• Any contraindications for the mother or the foetus to stop labour or prolong pregnancy or any maternal or foetal conditions likely to indicate iatrogenic delivery.
• Use of cervical cerclage or a pessary in situ in the current pregnancy.
• The Subject has any condition which in the opinion of the PI constitutes a risk or a contraindication for the participation of the subject in the trial.

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 a single oral dose a day for up to 7 days.
Experimental: OBE001	Drug: OBE001; OBE001 dispersible tablets for a single oral dose a day for up to 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
EFFICACY ENDPOINTS: Incidence of women delivering within 7 days post first dose	within 7 days of first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFFICACY ENDPOINTS: Incidence of women delivering within 48 hours post first dose		within 48 hours of first dose
EFFICACY ENDPOINTS: Incidence of women delivering before gestational age 37^0/7 weeks		up to 3 weeks post first dose
EFFICACY ENDPOINTS: Progression of uterine contractions from pre-dose to 6 hours and 24 hours post first dose	Contractions measured by tocodynamometry.	up to 24 hours post first dose
EFFICACY ENDPOINTS: Assessment of maternal and foetal exposure to OBE001 (Maternal plasma concentrations of OBE001)	Maternal plasma concentrations of OBE001 on Day 1 (2 hours post first dose), on Day 2 (pre-dose and 2 hours post-dose) on Day 3 (pre-dose), Day 7 (post-dose) and at the time of delivery. Umbilical cord plasma concentration of OBE001 at the time of delivery.	up to 7 weeks post first dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAFETY ENDPOINTS: Evaluation of the maternal safety of OBE001 (Maternal incidence of adverse events (AEs), treatment-emergent adverse events (TEAEs), clinically significant changes in laboratory safety tests, 12-lead ECGs morphology or vital signs)	Maternal incidence of adverse events (AEs), treatment-emergent adverse events (TEAEs), clinically significant changes in laboratory safety tests, 12-lead ECGs morphology or vital signs from Day 1 until 28 days after birth or term whichever is later.	up to 28 days post expected term date
SAFETY ENDPOINTS: Evaluation of the foetal safety of OBE001 (clinically significant changes in growth retardation and/or foetal heart rate monitoring and/or Amniotic Fluid Indices (AFI)	Incidence of foetal distress as determined by clinically significant changes in growth retardation and/or foetal heart rate monitoring and/or Amniotic Fluid Indices (AFI) from Day 1 to Day 14 or birth, whichever is earlier	up to 14 days post first dose or birth whichever is earlier
SAFETY ENDPOINTS: Evaluation of the newborn neonatal morbidity	Incidence of infants experiencing adverse events assessed by vital signs, temperature, APGAR score, weight and head circumference at birth as well as measures of neonatal morbidity from birth until 28 days after birth or term whichever is later	up to 28 days post expected term date
SAFETY ENDPOINTS: Evaluation of infant neurodevelopmental outocme.	Incidence of infants with one or more Ages and Stages Questionnaire-3 domain score(s) below the cutoff at 6, 12, and 24 months, adjusted for gestational age.	up to 2 years after birth

Collaborators and Investigators

• Sponsor: ObsEva SA

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: December 22, 2014
• First Submitted That Met QC Criteria: December 24, 2014
• First Posted (Estimate): December 25, 2014

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 3, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Premature Birth; Premature Obstetric Labor
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Premature Birth; Obstetric Labor, Premature
• Other Study ID Numbers: 14-OBE001-016