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PoC Study of OBE022 in Threatened Preterm Labour (PROLONG)

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ClinicalTrials.gov Identifier: NCT03369262
Recruitment Status : Active, not recruiting
First Posted : December 11, 2017
Last Update Posted : June 7, 2021
Sponsor:
Collaborators:
SCOPE International AG
Iqvia Pty Ltd
Cytel Inc.
PHINC DEVELOPMENT
Information provided by (Responsible Party):
ObsEva SA

Tracking Information
First Submitted Date  ICMJE November 30, 2017
First Posted Date  ICMJE December 11, 2017
Last Update Posted Date June 7, 2021
Actual Study Start Date  ICMJE January 10, 2018
Actual Primary Completion Date July 8, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2017)
  • Incidence of delivery within 2 days (48 h) from start of IMP administration [ Time Frame: 48 hours ]
  • Incidence of delivery within 7 days (168 h) from start of IMP administration [ Time Frame: 168 hours ]
  • Incidence of delivery before 37 weeks of GA [ Time Frame: Up to 13 weeks from start of IMP administration ]
  • Time to delivery measured from start of IMP administration [ Time Frame: Up to 17 weeks from start of IMP administration ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: June 4, 2021)
  • Maternal incidence of AEs from Day 1 until 28 days after birth. [ Time Frame: 28 days after birth ]
  • Maternal incidence of TEAEs from Day 1 until 28 days after birth. [ Time Frame: 28 days after birth ]
  • Maternal incidence of clinically significant changes in laboratory safety tests, from Day 1 until 28 days after birth. [ Time Frame: 28 days after birth ]
  • Maternal incidence of clinically significant changes in vital signs, from Day 1 until 28 days after birth. [ Time Frame: 28 days after birth ]
  • 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 ]
  • 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 ]
  • Incidence of infants experiencing adverse events from birth until 28 days after birth. [ Time Frame: Up to 28 days after birth ]
  • 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 ]
  • Apgar score. [ Time Frame: At birth, at 1 minute and 5 minute ]
    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.
  • Weight. [ Time Frame: At birth and 28 days after birth. ]
  • Head circumference. [ Time Frame: At birth and 28 days after birth. ]
  • Incidence of infants experiencing prematurity-related events [ Time Frame: At birth. ]
  • Incidence of duration of hospitalization and or re-admission to hospital. [ Time Frame: Up to 28 days after birth. ]
  • 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. [ Time Frame: Up to 24 months ]
    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
  • 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 ]
  • Pharmacokinetic parameters of OBE022/OBE002 at Day 7 [ Time Frame: Day 7 ]
    Area under the curve (AUC)
  • Pharmacokinetic parameters of OBE022/OBE002 at Day 7 [ Time Frame: Day 7 ]
    Maximal concentration (Cmax)
  • Pharmacokinetic parameters of OBE022/OBE002 at Day 7 [ Time Frame: Day 7 ]
    Half-life.
  • 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 ]
  • 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. ]
Original Other Pre-specified Outcome Measures
 (submitted: December 8, 2017)
  • Maternal incidence of AEs from Day 1 until 28 days after birth. [ Time Frame: 28 days after birth ]
  • Maternal incidence of TEAEs from Day 1 until 28 days after birth. [ Time Frame: 28 days after birth ]
  • Maternal incidence of clinically significant changes in laboratory safety tests, from Day 1 until 28 days after birth. [ Time Frame: 28 days after birth ]
  • Maternal incidence of clinically significant changes in vital signs, from Day 1 until 28 days after birth. [ Time Frame: 28 days after birth ]
  • 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 ]
  • In Part A only: Pulsatility index of the ductus arteriosus on Day 1 to 3 and Day 7 from IMP start. [ Time Frame: Up to 7 days after start of IMP administration ]
  • In Part A only: Foetal combined cardiac output on Day 1 to 3 and Day 7 from IMP start. [ Time Frame: Up to 7 days after start of IMP administration ]
  • Incidence of infants experiencing adverse events from birth until 28 days after birth. [ Time Frame: Up to 28 days after birth ]
  • 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 ]
  • Apgar score. [ Time Frame: At birth ]
  • Weight. [ Time Frame: At birth and 28 days after birth. ]
  • Head circumference. [ Time Frame: At birth and 28 days after birth. ]
  • Incidence of stillborn. [ Time Frame: At birth. ]
  • Incidence of neonatal death. [ Time Frame: Up to 28 days after birth. ]
  • Incidence of duration of hospitalization and or re-admission to hospital [ Time Frame: Up to 28 days after birth. ]
  • Incidence of assisted ventilation [ Time Frame: Up to 28 days after birth. ]
  • Incidence of respiratory distress syndrome [ Time Frame: Up to 28 days after birth. ]
  • Incidence of bronchopulmonary dysplasia. [ Time Frame: Up to 28 days after birth. ]
  • Incidence of grade 1-4 intra-ventricular haemorrhage. [ Time Frame: Up to 28 days after birth. ]
  • Incidence of periventricular leukomalacia or periventricular echogenicity [ Time Frame: Up to 28 days after birth. ]
  • Incidence of renal impairment [ Time Frame: Up to 28 days after birth. ]
  • Incidence of cardiac abnormalities [ Time Frame: Up to 28 days after birth. ]
  • Incidence of necrotizing enterocolitis [ Time Frame: Up to 28 days after birth. ]
  • Incidence of difficulty in thermoregulation [ Time Frame: Up to 28 days after birth. ]
  • Incidence of difficulty in feeding [ Time Frame: Up to 28 days after birth. ]
  • Incidence of jaundice [ Time Frame: Up to 28 days after birth. ]
  • 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. [ Time Frame: Up to 24 months ]
  • 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 ]
  • Area under the curve (AUC). [ Time Frame: Day 7 ]
  • Maximal concentration (Cmax). [ Time Frame: Day 7 ]
  • Half-life. [ Time Frame: Day 7 ]
  • 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 ]
  • 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. ]
 
Descriptive Information
Brief Title  ICMJE PoC Study of OBE022 in Threatened Preterm Labour
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
A phase 2a, double-blind, parallel group, randomised, placebo controlled, added-on to atosiban.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Matching placebo.
Primary Purpose: Treatment
Condition  ICMJE Preterm Labor
Intervention  ICMJE
  • Drug: OBE022
    Oral
  • Drug: Placebos
    Oral
  • Drug: Atosiban
    I.V.
Study Arms  ICMJE
  • Experimental: Active

    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.

    Interventions:
    • Drug: OBE022
    • Drug: Atosiban
  • Active Comparator: Placebo

    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.

    Interventions:
    • Drug: Placebos
    • Drug: Atosiban
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 4, 2021)
115
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2017)
130
Estimated Study Completion Date  ICMJE August 2022
Actual Primary Completion Date July 8, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   Finland,   Israel,   Russian Federation,   Spain,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03369262
Other Study ID Numbers  ICMJE 17-OBE022-003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party ObsEva SA
Study Sponsor  ICMJE ObsEva SA
Collaborators  ICMJE
  • SCOPE International AG
  • Iqvia Pty Ltd
  • Cytel Inc.
  • PHINC DEVELOPMENT
Investigators  ICMJE Not Provided
PRS Account ObsEva SA
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP