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PoC Study of OBE022 in Threatened Preterm Labour (PROLONG)

Primary Purpose

Preterm Labor

Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
OBE022
Placebos
Atosiban
Sponsored by
ObsEva SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Preterm Labor focused on measuring preterm labor, preterm birth, premature birth, tocolysis, prostaglandin F2α antagonist, PGF2α, tocolytic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Key Inclusion Criteria:

Part A

  • Pregnant females aged ≥ 18 years
  • Patients with a singleton or twin pregnancy
  • Gestational age between 28 0/7 and 33 6/7
  • Administered or prescribed atosiban for the treatment of preterm labour

Part B

  • Pregnant females aged ≥ 18 years
  • Patients with a singleton or twin pregnancy
  • Gestational age between 24 0/7 and 33 6/7
  • Administered or prescribed atosiban for the treatment of preterm labour
  • ≥4 uterine contractions per 30 minutes
  • Cervical dilatation of 1 to 4 cm inclusive

  • At least one of the following signs of preterm labour:

    1. positive IGFBP-1 or fœtal Fibronectin test
    2. cervical length ≤ 25mm
    3. progressive cervical change

Key Exclusion Criteria:

  • Fœtal death in utero in current or previous pregnancy after gestational week 24 or expected high risk of fœtal death in the coming days
  • Oligohydramnios
  • Known pathological Doppler ultrasound of the umbilical artery

  • Any contraindications for the mother or the fœtus to stop labour or prolong pregnancy or any maternal or fœtal conditions likely to indicate iatrogenic delivery in the next 7 days, including but not limited to:

    1. Premature rupture of membranes
    2. Evidence or suspicion of abruptio placenta
    3. Signs and/or symptoms of chorio-amnionitis
    4. Pre-eclampsia, eclampsia or HELLP-syndrome
  • Use of cervical cerclage in the current pregnancy or a pessary in situ
  • Current use of anti-hypertensive medication
  • Treatment with other tocolytics within specified time before the baseline assessment of uterine contractions

Sites / Locations

  • Gynekologicko-porodnická klinika Fakultní nemocnice Brno
  • Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze
  • Ústav pro péči o matku a dítě
  • Helsinki Universisty Hospital
  • Hilel Yafe Medical Center, Maternal Fetal Unit
  • Rambam Medical Center, Maternal Fetal Unit
  • Meir Medical Center, Obstetrics and Gynecology Department
  • Rabin Medical Center, Fetal-Maternal Medicine, Helen Schneider's Hospital for Women
  • Moscow Regional Perinatal Center
  • Kazan State Medical University
  • City clinical hospital № 15 named after O. M. Filatov of Healthcare Department of Moscow
  • Perinatal center of the City Clinical Hospital #24
  • Hospital La Paz
  • Hospital Clínico Universitario Virgen de la Arrixaca
  • Hospital Clínico Universitario de Santiago
  • Hospital Universitari i Politècnic La Fe
  • Hanoi Obstetrics and Gynecology Hospital
  • My Duc Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Active

Placebo

Arm Description

OBE022 plus atosiban: OBE022 will be given orally from Day 1 to Day 7. OBE022 treatment will be initiated ideally simultaneously or at a maximum within 24 h after atosiban start. Loading dose: 1 000 mg on Day 1. Maintenance dose on Day 1: 500 mg in the evening if loading dose was administered in the morning. If loading dose was administered in the afternoon, then the next dose will take place on the morning of Day 2. Maintenance dose from Day 2 to Day 7: 500 mg twice a day (only morning dose on Day 7) Atosiban will be administered over 48h as per label.

OBE022 matching placebo plus atosiban: OBE022 matching placebo administration will follow the same regimen as the active group. Atosiban will be administered over 48h as per label.

Outcomes

Primary Outcome Measures

Incidence of delivery within 2 days (48 h) from start of IMP administration
Incidence of delivery within 7 days (168 h) from start of IMP administration
Incidence of delivery before 37 weeks of GA
Time to delivery measured from start of IMP administration

Secondary Outcome Measures

Full Information

First Posted
November 30, 2017
Last Updated
June 4, 2021
Sponsor
ObsEva SA
Collaborators
Scope International AG, Iqvia Pty Ltd, Cytel Inc., PhinC Development
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1. Study Identification

Unique Protocol Identification Number
NCT03369262
Brief Title
PoC Study of OBE022 in Threatened Preterm Labour
Acronym
PROLONG
Official Title
A Phase 2a, Double-blind, Parallel Group, Randomised, Placebo Controlled, Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of OBE022 added-on to Atosiban, After Oral Administration in Pregnant Women With Threatened Spontaneous Preterm Labour
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Unknown status
Study Start Date
January 10, 2018 (Actual)
Primary Completion Date
July 8, 2020 (Actual)
Study Completion Date
August 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ObsEva SA
Collaborators
Scope International AG, Iqvia Pty Ltd, Cytel Inc., PhinC Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a proof-of-concept study in 2 parts. In Part A, patients will receive OBE022 open-label in order to assess the safety and pharmacokinetics in pregnant women with spontaneous preterm labour with a gestational age between 28 0/7 and 33 6/7 weeks. Part B has a double-blind, randomised, placebo controlled, parallel group and multicentre design and will assess the efficacy, safety and pharmacokinetics in pregnant women with threatened spontaneous preterm labour with a gestational age between 24 0/7 and 33 6/7 weeks. All patients in part A and part B must receive atosiban infusion for 48 hours as standard of care treatment. Patients from Part A will receive OBE022 open label. Patients from Part B will be randomised to receive OBE022 or matching placebo. IMP treatment duration will be up to 7 days. IMP treatment will be stopped in case of delivery prior to Day 7.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preterm Labor
Keywords
preterm labor, preterm birth, premature birth, tocolysis, prostaglandin F2α antagonist, PGF2α, tocolytic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A phase 2a, double-blind, parallel group, randomised, placebo controlled, added-on to atosiban.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Matching placebo.
Allocation
Randomized
Enrollment
115 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active
Arm Type
Experimental
Arm Description
OBE022 plus atosiban: OBE022 will be given orally from Day 1 to Day 7. OBE022 treatment will be initiated ideally simultaneously or at a maximum within 24 h after atosiban start. Loading dose: 1 000 mg on Day 1. Maintenance dose on Day 1: 500 mg in the evening if loading dose was administered in the morning. If loading dose was administered in the afternoon, then the next dose will take place on the morning of Day 2. Maintenance dose from Day 2 to Day 7: 500 mg twice a day (only morning dose on Day 7) Atosiban will be administered over 48h as per label.
Arm Title
Placebo
Arm Type
Active Comparator
Arm Description
OBE022 matching placebo plus atosiban: OBE022 matching placebo administration will follow the same regimen as the active group. Atosiban will be administered over 48h as per label.
Intervention Type
Drug
Intervention Name(s)
OBE022
Intervention Description
Oral
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
Oral
Intervention Type
Drug
Intervention Name(s)
Atosiban
Intervention Description
I.V.
Primary Outcome Measure Information:
Title
Incidence of delivery within 2 days (48 h) from start of IMP administration
Time Frame
48 hours
Title
Incidence of delivery within 7 days (168 h) from start of IMP administration
Time Frame
168 hours
Title
Incidence of delivery before 37 weeks of GA
Time Frame
Up to 13 weeks from start of IMP administration
Title
Time to delivery measured from start of IMP administration
Time Frame
Up to 17 weeks from start of IMP administration
Other Pre-specified Outcome Measures:
Title
Maternal incidence of AEs from Day 1 until 28 days after birth.
Time Frame
28 days after birth
Title
Maternal incidence of TEAEs from Day 1 until 28 days after birth.
Time Frame
28 days after birth
Title
Maternal incidence of clinically significant changes in laboratory safety tests, from Day 1 until 28 days after birth.
Time Frame
28 days after birth
Title
Maternal incidence of clinically significant changes in vital signs, from Day 1 until 28 days after birth.
Time Frame
28 days after birth
Title
Incidence of AEs indicating fœtal distress such as growth retardation and/or changes in fœtal heart rate monitoring and/or amniotic fluid index (AFI) from Day 1 to Day 7 and Day 14 (or earlier if birth).
Time Frame
Up to 14 days after start of IMP administration
Title
In Part A only: Incidence of fœtal adverse events in relation with the cardiovascular function assessed by Doppler ultrasound on Day 1 to 3 and Day 7 from IMP start.
Time Frame
Up to 7 days after start of IMP administration
Title
Incidence of infants experiencing adverse events from birth until 28 days after birth.
Time Frame
Up to 28 days after birth
Title
Incidence of infants experiencing clinical significant changes in vital signs from birth until 28 days after birth.
Time Frame
Up to 28 days after birth
Title
Apgar score.
Description
The score is a rapid method for assessing a neonate immediately after birth. Elements of the Apgar score include color, heart rate, reflexes, muscle tone, and respiration, each weighted evenly and assigned a value of 0, 1, or 2. The components are then added together to give a total score (0 to 10) that is recorded at 1 and 5 minutes after birth.
Time Frame
At birth, at 1 minute and 5 minute
Title
Weight.
Time Frame
At birth and 28 days after birth.
Title
Head circumference.
Time Frame
At birth and 28 days after birth.
Title
Incidence of infants experiencing prematurity-related events
Time Frame
At birth.
Title
Incidence of duration of hospitalization and or re-admission to hospital.
Time Frame
Up to 28 days after birth.
Title
Incidence of infants with one or more Ages and Stages Questionnaire® domain score(s) below the cut-off score at 6 months, 12 months and 24 months of age, adjusted for gestational age at birth.
Description
The Ages and Stages Questionnaire (ASQ) is a parent-completed questionnaire designed to be used as a general developmental screening tool. The ASQ-3 covers five areas of child development that includes: personal social, gross motor, fine motor, problem solving, and communication. Parents complete the questionnaire independent of professionals, indicating for each item "yes" if child performs the item, "sometimes" indicating an occasional or emerging skill, or "not yet" indicating that the child does not yet perform the behavior
Time Frame
Up to 24 months
Title
Plasma concentration of OBE022/OBE002 at Day 1, Day 2, Day 3 and Day 7.
Time Frame
Up to 7 days after start of IMP administration
Title
Pharmacokinetic parameters of OBE022/OBE002 at Day 7
Description
Area under the curve (AUC)
Time Frame
Day 7
Title
Pharmacokinetic parameters of OBE022/OBE002 at Day 7
Description
Maximal concentration (Cmax)
Time Frame
Day 7
Title
Pharmacokinetic parameters of OBE022/OBE002 at Day 7
Description
Half-life.
Time Frame
Day 7
Title
Fœtal (cord blood)-maternal OBE002 concentration ratio at the time of delivery for patients who received IMP treatment within the previous 24 h.
Time Frame
Day of delivery
Title
Changes in uterine contractions as assessed by electrohysterography, tocodynamometry or abdominal palpation at each hour during the first 6 hours after IMP start.
Time Frame
Up to 6 hours after IMP start.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Part A Pregnant females aged ≥ 18 years Patients with a singleton or twin pregnancy Gestational age between 28 0/7 and 33 6/7 Administered or prescribed atosiban for the treatment of preterm labour Part B Pregnant females aged ≥ 18 years Patients with a singleton or twin pregnancy Gestational age between 24 0/7 and 33 6/7 Administered or prescribed atosiban for the treatment of preterm labour ≥4 uterine contractions per 30 minutes Cervical dilatation of 1 to 4 cm inclusive At least one of the following signs of preterm labour: positive IGFBP-1 or fœtal Fibronectin test cervical length ≤ 25mm progressive cervical change Key Exclusion Criteria: Fœtal death in utero in current or previous pregnancy after gestational week 24 or expected high risk of fœtal death in the coming days Oligohydramnios Known pathological Doppler ultrasound of the umbilical artery Any contraindications for the mother or the fœtus to stop labour or prolong pregnancy or any maternal or fœtal conditions likely to indicate iatrogenic delivery in the next 7 days, including but not limited to: Premature rupture of membranes Evidence or suspicion of abruptio placenta Signs and/or symptoms of chorio-amnionitis Pre-eclampsia, eclampsia or HELLP-syndrome Use of cervical cerclage in the current pregnancy or a pessary in situ Current use of anti-hypertensive medication Treatment with other tocolytics within specified time before the baseline assessment of uterine contractions
Facility Information:
Facility Name
Gynekologicko-porodnická klinika Fakultní nemocnice Brno
City
Brno
Country
Czechia
Facility Name
Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze
City
Praha
Country
Czechia
Facility Name
Ústav pro péči o matku a dítě
City
Praha
Country
Czechia
Facility Name
Helsinki Universisty Hospital
City
Helsinki
Country
Finland
Facility Name
Hilel Yafe Medical Center, Maternal Fetal Unit
City
Haifa
Country
Israel
Facility Name
Rambam Medical Center, Maternal Fetal Unit
City
Haifa
Country
Israel
Facility Name
Meir Medical Center, Obstetrics and Gynecology Department
City
Kfar Saba
Country
Israel
Facility Name
Rabin Medical Center, Fetal-Maternal Medicine, Helen Schneider's Hospital for Women
City
Petah tikva
Country
Israel
Facility Name
Moscow Regional Perinatal Center
City
Balašicha
Country
Russian Federation
Facility Name
Kazan State Medical University
City
Kazan
Country
Russian Federation
Facility Name
City clinical hospital № 15 named after O. M. Filatov of Healthcare Department of Moscow
City
Moscow
Country
Russian Federation
Facility Name
Perinatal center of the City Clinical Hospital #24
City
Moscow
Country
Russian Federation
Facility Name
Hospital La Paz
City
Madrid
Country
Spain
Facility Name
Hospital Clínico Universitario Virgen de la Arrixaca
City
Murcia
Country
Spain
Facility Name
Hospital Clínico Universitario de Santiago
City
Santiago De Compostela
Country
Spain
Facility Name
Hospital Universitari i Politècnic La Fe
City
Valencia
Country
Spain
Facility Name
Hanoi Obstetrics and Gynecology Hospital
City
Hanoi
Country
Vietnam
Facility Name
My Duc Hospital
City
Ho Chi Minh City
Country
Vietnam

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35947046
Citation
Wilson A, Hodgetts-Morton VA, Marson EJ, Markland AD, Larkai E, Papadopoulou A, Coomarasamy A, Tobias A, Chou D, Oladapo OT, Price MJ, Morris K, Gallos ID. Tocolytics for delaying preterm birth: a network meta-analysis (0924). Cochrane Database Syst Rev. 2022 Aug 10;8(8):CD014978. doi: 10.1002/14651858.CD014978.pub2.
Results Reference
derived

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PoC Study of OBE022 in Threatened Preterm Labour

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