PoC Study of OBE022 in Threatened Preterm Labour

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Preterm Labor

Intervention / Treatment
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* Drug: OBE022
* Drug: Placebos
* Drug: Atosiban


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A phase 2a, double-blind, parallel group, randomised, placebo controlled, added-on to atosiban.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>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. | Drug: OBE022<br>* Oral<br>Drug: Atosiban<br>* I.V.<br>|
| Active Comparator: Placebo<br>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. | Drug: Placebos<br>* Oral<br>Drug: Atosiban<br>* I.V.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preterm labor, preterm birth, premature birth, tocolysis, prostaglandin F2α antagonist, PGF2α, tocolytic