PoC Study of OBE022 in Threatened Preterm Labour

Preterm Labor Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03369262
• Other study ID #: 17-OBE022-003
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 10, 2018
• Est. completion date: August 2022

Study information

• Verified date: June 2021
• Source: ObsEva SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 115
• Est. completion date: August 2022
• Est. primary completion date: July 8, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Obstetric Labor, Premature
• Premature Birth
• Preterm Labor

Intervention

Drug:
• OBE022
Oral
• Placebos
Oral
• Atosiban
I.V.

Locations

Country	Name	City	State
Czechia	Gynekologicko-porodnická klinika Fakultní nemocnice Brno	Brno
Czechia	Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze	Praha
Czechia	Ústav pro péci o matku a díte	Praha
Finland	Helsinki Universisty Hospital	Helsinki
Israel	Hilel Yafe Medical Center, Maternal Fetal Unit	Haifa
Israel	Rambam Medical Center, Maternal Fetal Unit	Haifa
Israel	Meir Medical Center, Obstetrics and Gynecology Department	Kfar Saba
Israel	Rabin Medical Center, Fetal-Maternal Medicine, Helen Schneider's Hospital for Women	Petah tikva
Russian Federation	Moscow Regional Perinatal Center	Balašicha
Russian Federation	Kazan State Medical University	Kazan
Russian Federation	City clinical hospital ? 15 named after O. M. Filatov of Healthcare Department of Moscow	Moscow
Russian Federation	Perinatal center of the City Clinical Hospital #24	Moscow
Spain	Hospital La Paz	Madrid
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Clínico Universitario de Santiago	Santiago De Compostela
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Vietnam	Hanoi Obstetrics and Gynecology Hospital	Hanoi
Vietnam	My Duc Hospital	Ho Chi Minh City

Sponsors (5)

Lead Sponsor	Collaborator
ObsEva SA	Cytel Inc., Iqvia Pty Ltd, PHINC DEVELOPMENT, SCOPE International AG

Countries where clinical trial is conducted

Czechia,  Finland,  Israel,  Russian Federation,  Spain,  Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maternal incidence of AEs from Day 1 until 28 days after birth.		28 days after birth
Other	Maternal incidence of TEAEs from Day 1 until 28 days after birth.		28 days after birth
Other	Maternal incidence of clinically significant changes in laboratory safety tests, from Day 1 until 28 days after birth.		28 days after birth
Other	Maternal incidence of clinically significant changes in vital signs, from Day 1 until 28 days after birth.		28 days after birth
Other	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
Other	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
Other	Incidence of infants experiencing adverse events from birth until 28 days after birth.		Up to 28 days after birth
Other	Incidence of infants experiencing clinical significant changes in vital signs from birth until 28 days after birth.		Up to 28 days after birth
Other	Apgar score.	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.	At birth, at 1 minute and 5 minute
Other	Weight.		At birth and 28 days after birth.
Other	Head circumference.		At birth and 28 days after birth.
Other	Incidence of infants experiencing prematurity-related events		At birth.
Other	Incidence of duration of hospitalization and or re-admission to hospital.		Up to 28 days after birth.
Other	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.	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	Up to 24 months
Other	Plasma concentration of OBE022/OBE002 at Day 1, Day 2, Day 3 and Day 7.		Up to 7 days after start of IMP administration
Other	Pharmacokinetic parameters of OBE022/OBE002 at Day 7	Area under the curve (AUC)	Day 7
Other	Pharmacokinetic parameters of OBE022/OBE002 at Day 7	Maximal concentration (Cmax)	Day 7
Other	Pharmacokinetic parameters of OBE022/OBE002 at Day 7	Half-life.	Day 7
Other	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
Other	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.
Primary	Incidence of delivery within 2 days (48 h) from start of IMP administration		48 hours
Primary	Incidence of delivery within 7 days (168 h) from start of IMP administration		168 hours
Primary	Incidence of delivery before 37 weeks of GA		Up to 13 weeks from start of IMP administration
Primary	Time to delivery measured from start of IMP administration		Up to 17 weeks from start of IMP administration