oral treatment of threatened spontaneous preterm labour in weeks 24 to 34 of pregnancy MedDRA version: 20.1 Level: LLT Classification code 10075863 Term: Preterm labor System Organ Class: 100000004868
Conditions
Interventions
Product Name: OBE022
Product Code: OBE022
Pharmaceutical Form: Granules for oral suspension
INN or Proposed INN: NA
CAS Number: 2005486-32-6
Current Sponsor code: OBE022
Other descriptive name: OBE022
Sponsors
ObsEva SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A 1. Provision of written informed consent to participate as shown by a signature on the patient consent form 2. Be able and willing to comply with the requirements of the protocol 3. Pregnant females aged = 18 years 4. Patients with a singleton or twin pregnancy 5. Gestational age between 28 (0/7) and 33 (6/7), as confirmed by a first trimester ultrasound scan or fertilization date. In situations where this information is not readily available, Investigator may use best clinical judgement or verbal history from the patient to be confirmed through medical records as soon as possible after inclusion 6. Administered or prescribed atosiban for the treatment of preterm labour (note that IMP treatment should be initiated ideally simultaneously or at a maximum within 24 h after atosiban start) Part B 1. Provision of written informed consent to participate as shown by a signature on the patient consent form 2. Be able and willing to comply with the requirements of the protocol 3. Pregnant females aged = 18 years. 4. Patients with a singleton or twin pregnancy 5. Gestational age between 24 (0/7) and 33 (6/7), as confirmed by a first trimester US scan or fertilization date. In situations where this information is not readily available, the Investigator may use best clinical judgement or verbal history from the patient to be confirmed through medical records as soon as possible after randomisation 6. =4 uterine contractions per 30 minutes, measured by electrohysterography, tocodynamometry or abdominal palpation * 7. Cervical dilatation of 1 to 4 cm inclusive * 8. At least one of the following signs of preterm labour * : a) positive IGFBP-1 or fœtal Fibronectin test b) cervical length = 25mm c) progressive cervical change 9. Administered or prescribed atosiban for the treatment of preterm labour (note that IMP treatment should be initiated ideally simultaneously or at a maximum within 24 h after atosiban start) * For criteria 6, 7 and 8, each criterion must be met at least once anytime between the 3 hours preceding atosiban start and first IMP intake. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 130 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: To be eligible for inclusion in this study the patients must not meet any of the following criteria: 1. Fœtal death in utero in current or previous pregnancy after gestational week 24 or expected high risk of fœtal death in the coming days 2. Fœtal weight outside 2 standard deviations for GA based on ultrasound 3. Oligohydramnios 4. Known pathological Doppler ultrasound of the umbilical artery 5. 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: a) Premature rupture of membranes b) Evidence or suspicion of abruptio placenta c) Signs and/or symptoms of chorio-amnionitis d) Pre-eclampsia, eclampsia or HELLP-syndrome 6. Any condition which in the opinion of the Investigator constitutes a risk or a contraindication for the participation of the patient in the trial or that could interfere with the trial objectives, conduct or evaluation, including: a) Any clinically significant abnormality in the results of the screening safety laboratory tests, including AST, ALT, GGT or total bilirubin > ×2 ULN b) Any clinically significant and trial relevant abnormality in the results of the screening physical examination including a gynaecological examination 7. The patient has known positive results from virology tests for HBsAg (not due to vaccination), HCV or HIV 1 or 2. However, patients who have resolved hepatitis B infection may be enrolled in the study 8. The patient had a BMI = 35 kg/m2 prior to start of current pregnancy or had a bariatric surgery 9. Any condition likely to hinder drug absorption 10. Use of cervical cerclage in the current pregnancy or a pessary in situ (not applicable in Part A) 11. Current use of anti-hypertensive medication 12. Treatment with other tocolytics within specified time before the baseline assessment of uterine contractions i.e. a) nifedipine (not long acting) in the previous 6 hours b) ritodrine, fenoterol, other betamimetics, indomethacin, other oral or injectable NSAIDs, long acting nifedipine, other calcium channel blockers, and nitric oxide donors in the previous 24 hours c) nicardipine in the previous 2 weeks d) any other drug given for tocolysis (within 5 half-lives of the agent before IMP start) 13. Known allergy or hypersensitivity to the active substance or any of the ingredients of the study drug 14. History of or current (within the past 12 months) known problem with alcohol or drug abuse 15. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of uncooperative attitude 16. Currently participating or have participated in another clinical trial (investigational drug or medical device) within 30 days prior to screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: To evaluate the - maternal and fœtal safety and tolerability of OBE022 - pharmacokinetics of OBE022/OBE002 in pregnant women with threatened spontaneous preterm labour To describe - time to delivery - uterine contractions in pregnant women with threatened spontaneous preterm labour treated with OBE022 Part B - To compare the efficacy of OBE022 to placebo to delay preterm birth - To evaluate the maternal and fœtal safety and tolerability of OBE022 - To evaluate the pharmacokinetics of OBE022/OBE002 - To assess the effect of OBE022 on uterine contractions in pregnant women with threatened spontaneous preterm labour ;Secondary Objective: Not applicable;Primary end point(s): As this study is a proof-of-concept study and the results as a whole will be used to inform the further clinical development of OBE022, a primary efficacy endpoint has not been defined Efficacy End Point: • Incidence of delivery within 2 days (48 h) from start of IMP administration • Incidence of delivery within 7 days (168 h) from start of IMP administration • Incidence of delivery before 37 weeks of GA • Time to delivery measured from start of IMP administration Safety Endpoint: • Maternal incidence of AEs, TEAEs, clinically significant changes in laboratory safety tests, vital signs from Day 1 until 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) or amniotic fluid volume (in twins) from Day 1 to Day 7 and Day 14 (or earlier if birth). • 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. • Incidence of infants experiencing adverse events, clinical significant changes in vital signs. Apgar score, weight and head circumference at birth as well as a measure of neonatal morbidity from birth until 28 days after bir | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not Applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Czech Republic, Finland, Israel, Poland, Russian Federation, Spain, Vietnam
Contacts
Public ContactClinical Trial Director
ObsEva SA
Outcome results
None listed