Preterm Labor
Conditions
Keywords
preterm labor, preterm birth, premature birth, tocolysis, prostaglandin F2α antagonist, PGF2α, tocolytic
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.
Interventions
DRUGOBE022
Oral
DRUGPlacebos
Oral
DRUGAtosiban
I.V.
Sponsors
Scope International AG
Iqvia Pty Ltd
Cytel Inc.
PhinC Development
ObsEva SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Matching placebo.
Intervention model description
A phase 2a, double-blind, parallel group, randomised, placebo controlled, added-on to atosiban.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of delivery within 2 days (48 h) from start of IMP administration | 48 hours |
| Incidence of delivery within 7 days (168 h) from start of IMP administration | 168 hours |
| Incidence of delivery before 37 weeks of GA | Up to 13 weeks from start of IMP administration |
| Time to delivery measured from start of IMP administration | Up to 17 weeks from start of IMP administration |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maternal incidence of TEAEs from Day 1 until 28 days after birth. | 28 days after birth | — |
| Maternal incidence of clinically significant changes in laboratory safety tests, from Day 1 until 28 days after birth. | 28 days after birth | — |
| Maternal incidence of clinically significant changes in vital signs, from Day 1 until 28 days after birth. | 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). | 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. | Up to 7 days after start of IMP administration | — |
| Incidence of infants experiencing adverse events from birth until 28 days after birth. | Up to 28 days after birth | — |
| Incidence of infants experiencing clinical significant changes in vital signs from birth until 28 days after birth. | Up to 28 days after birth | — |
| Weight. | At birth and 28 days after birth. | — |
| Incidence of duration of hospitalization and or re-admission to hospital. | 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. | 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. | Up to 7 days after start of IMP administration | — |
| Pharmacokinetic parameters of OBE022/OBE002 at Day 7 | Day 7 | Area under the curve (AUC) |
| Fœtal (cord blood)-maternal OBE002 concentration ratio at the time of delivery for patients who received IMP treatment within the previous 24 h. | 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. | Up to 6 hours after IMP start. | — |
| Apgar score. | 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. |
| Head circumference. | At birth and 28 days after birth. | — |
| Incidence of infants experiencing prematurity-related events | At birth. | — |
| Maternal incidence of AEs from Day 1 until 28 days after birth. | 28 days after birth | — |
Countries
Czechia, Finland, Israel, Russia, Spain, Vietnam
Outcome results
None listed