Clinical trial NCT03369262: PoC Study of OBE022 in Threatened Preterm Labour
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Preterm Labor
Keywords: preterm labor
preterm birth
premature birth
tocolysis
prostaglandin F2α antagonist
PGF2α
tocolytic
Lead sponsor: ObsEva SA
Sponsor class: INDUSTRY
Collaborators: name: Scope International AG
name: Iqvia Pty Ltd
name: Cytel Inc.
name: PhinC Development
First posted: 2017-12-11
Enrollment: 115
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A phase 2a, double-blind, parallel group, randomised, placebo controlled, added-on to atosiban.
Primary purpose: TREATMENT

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.


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:

  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

Primary outcomes:
measure: Incidence of delivery within 2 days (48 h) from start of IMP administration
timeFrame: 48 hours
measure: Incidence of delivery within 7 days (168 h) from start of IMP administration
timeFrame: 168 hours
measure: Incidence of delivery before 37 weeks of GA
timeFrame: Up to 13 weeks from start of IMP administration
measure: Time to delivery measured from start of IMP administration
timeFrame: Up to 17 weeks from start of IMP administration
Secondary outcomes:
Other outcomes:
measure: Maternal incidence of AEs from Day 1 until 28 days after birth.
timeFrame: 28 days after birth
measure: Maternal incidence of TEAEs from Day 1 until 28 days after birth.
timeFrame: 28 days after birth
measure: Maternal incidence of clinically significant changes in laboratory safety tests, from Day 1 until 28 days after birth.
timeFrame: 28 days after birth
measure: Maternal incidence of clinically significant changes in vital signs, from Day 1 until 28 days after birth.
timeFrame: 28 days after birth
measure: 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).
timeFrame: Up to 14 days after start of IMP administration
measure: 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.
timeFrame: Up to 7 days after start of IMP administration
measure: Incidence of infants experiencing adverse events from birth until 28 days after birth.
timeFrame: Up to 28 days after birth
measure: Incidence of infants experiencing clinical significant changes in vital signs from birth until 28 days after birth.
timeFrame: Up to 28 days after birth
measure: Apgar score.
timeFrame: At birth, at 1 minute and 5 minute
measure: Weight.
timeFrame: At birth and 28 days after birth.
measure: Head circumference.
timeFrame: At birth and 28 days after birth.
measure: Incidence of infants experiencing prematurity-related events
timeFrame: At birth.
measure: Incidence of duration of hospitalization and or re-admission to hospital.
timeFrame: Up to 28 days after birth.
measure: 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.
timeFrame: Up to 24 months
measure: Plasma concentration of OBE022/OBE002 at Day 1, Day 2, Day 3 and Day 7.
timeFrame: Up to 7 days after start of IMP administration
measure: Pharmacokinetic parameters of OBE022/OBE002 at Day 7
timeFrame: Day 7
measure: Pharmacokinetic parameters of OBE022/OBE002 at Day 7
timeFrame: Day 7
measure: Pharmacokinetic parameters of OBE022/OBE002 at Day 7
timeFrame: Day 7
measure: Fœtal (cord blood)-maternal OBE002 concentration ratio at the time of delivery for patients who received IMP treatment within the previous 24 h.
timeFrame: Day of delivery
measure: Changes in uterine contractions as assessed by electrohysterography, tocodynamometry or abdominal palpation at each hour during the first 6 hours after IMP start.
timeFrame: Up to 6 hours after IMP start.
Locations:
city: Brno
country: Czechia
facility: Gynekologicko-porodnická klinika Fakultní nemocnice Brno
city: Praha
country: Czechia
facility: Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze
city: Praha
country: Czechia
facility: Ústav pro péči o matku a dítě
city: Helsinki
country: Finland
facility: Helsinki Universisty Hospital
city: Haifa
country: Israel
facility: Hilel Yafe Medical Center, Maternal Fetal Unit
city: Haifa
country: Israel
facility: Rambam Medical Center, Maternal Fetal Unit
city: Kfar Saba
country: Israel
facility: Meir Medical Center, Obstetrics and Gynecology Department
city: Petah tikva
country: Israel
facility: Rabin Medical Center, Fetal-Maternal Medicine, Helen Schneider's Hospital for Women
city: Balašicha
country: Russian Federation
facility: Moscow Regional Perinatal Center
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Moscow
country: Russian Federation
facility: City clinical hospital № 15 named after O. M. Filatov of Healthcare Department of Moscow
city: Moscow
country: Russian Federation
facility: Perinatal center of the City Clinical Hospital #24
city: Madrid
country: Spain
facility: Hospital La Paz
city: Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
city: Santiago De Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Hanoi
country: Vietnam
facility: Hanoi Obstetrics and Gynecology Hospital
city: Ho Chi Minh City
country: Vietnam
facility: My Duc Hospital
Study officials:
References:
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.