Clinical Trials Register

Summary
EudraCT Number:	2014-003217-28
Sponsor's Protocol Code Number:	14-OBE001-016
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-02-06
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2014-003217-28

A.3

Full title of the trial

A phase 2, double-blind, parallel group, randomised, placebo controlled, proof of concept study to assess the safety and efficacy of OBE001 after oral administration in pregnant women with threatened preterm labour.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A phase 2 study of OBE001 versus placebo in the delay of preterm birth.

A.3.2

Name or abbreviated title of the trial where available

TERM

A.4.1

Sponsor's protocol code number

14-OBE001-016

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02326146

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ObsEva SA
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ObsEva SA
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ObsEva SA
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Chemin des Aulx, 12
B.5.3.2	Town/ city	Plan-les-Ouates, Geneva
B.5.3.3	Post code	1228
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41225521550
B.5.5	Fax number	+41227432921
B.5.6	E-mail	clinicaltrials@obseva.ch

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	OBE001
D.3.2	Product code	OBE001
D.3.4	Pharmaceutical form	Dispersible tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	1477482-19-1
D.3.9.2	Current sponsor code	OBE001
D.3.9.3	Other descriptive name	OBE001
D.3.9.4	EV Substance Code	SUB130545
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Dispersible tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Treatment of preterm labour

E.1.1.1

Medical condition in easily understood language

Treatment of preterm labour

E.1.1.2

Therapeutic area

Body processes [G] - Reproductive physiologi cal processes [G08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	SOC
E.1.2	Classification code	10036585
E.1.2	Term	Pregnancy, puerperium and perinatal conditions
E.1.2	System Organ Class	10036585 - Pregnancy, puerperium and perinatal conditions

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the efficacy of OBE001 with placebo to delay preterm birth by 7 days.

E.2.2

Secondary objectives of the trial

- To compare the efficacy of OBE001 with placebo to delay preterm birth by 48 hours.
- To compare the efficacy of OBE001 with placebo to delay birth until gestational week 37.
- To assess maternal and foetal exposure to OBE001.
- To evaluate the effect of OBE001 on frequency of uterine contractions.

safety objectives:
- To evaluate the maternal and foetal safety of OBE001.
- To evaluate the newborn neonatal morbidity up to 28 days post expected term date.
- To evaluate infant neurodevelopmental outcome up to 2 years after birth.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Pregnant females aged ≥ 18 years.
2. Subjects with a singleton pregnancy.
3. Gestational age (GA) between 34 0/7 and 35 6/7 weeks as assessed by best obstetric estimate, and confirmed by a first trimester ultrasound (US)scan.
4. Subjects with ≥ 3 uterine contractions per 30 mins, each of which is at least 30 seconds in duration, as measured by tocodynamometry
5. Subjects with at least one of the following symptoms of preterm labour:
a. A positive foetal Fibronectin test (qualitative or ≥ 50 ng/mL for quantitative)
b. Cervical length ≤ 25 mm (by TVUS)
c. Cervical dilation of 2-4 cm.
d. If cervical dilation is < 2 cm: at least 25% effacement or increase of 1 cm in dilation.
6. Able to communicate well with the investigator and research staff and to comply with the requirements of the entire study.
7. Provision of written informed consent to participate as shown by a signature on the subject consent form.

E.4

Principal exclusion criteria

1. Foetal death in utero in current pregnancy or in previous pregnancy after gestational week 24 or expected high risk of foetal death in the coming days.
2. Any contraindications for the mother or the foetus to stop labour or prolong pregnancy or any maternal or foetal conditions likely to indicate iatrogenic delivery in the next 7 days, including:
a. Premature rupture of membranes
b. Evidence or suspicion of abruptio placenta
c. Signs and/or symptoms of chorio-amnionitis
d. Eclampsia or pre-eclampsia
e. Foetal distress as assessed by the investigator
3. The Subject has any condition which in the opinion of the PI constitutes a risk or a contraindication for the participation of the subject 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, alkaline phosphatase or total bilirubin > ×2 ULN for women in the 3rd trimester of pregnancy (to be confirmed within 24 hours of randomisation).
b. Any clinically significant and trial relevant abnormality in the results of the screening physical examination including a gynaecological examination.
c. Any subject for whom treatment with parenteral magnesium sulphate is anticipated during the treatment with OBE001.
d. The subject has known positive results from virology tests for HBsAg (not due to vaccination), HBcAb, HCV or HIV 1 or 2. However, subjects who have resolved hepatitis B infection may be enrolled in the study.
e. The Subject is prone to frequent, severe hypersensitivity to drugs.
f. Evidence of recent drug or alcohol abuse.
g. The Subject is planning to deliver in another location than the investigational site.
4. The Subject had a BMI ≥ 35 kg/m2 prior to current pregnancy.
5. Use of cervical cerclage in the current pregnancy or a pessary in situ
6. Treatment with other tocolytics within specified time before the baseline assessment of uterine contractions i.e.
a. 1 hour: atosiban
b. 6 hours: nifedipine (not long acting)
c. 24 hours: ritodrine, fenoterol, other betamimetics, indomethacin, other oral or injectable NSAIDs, long acting nifedipine, other calcium channel blockers, and nitric oxide donors
d. 2 weeks: nicardipine, parenteral magnesium sulphate.
7. Administration of any experimental drug during the current pregnancy.

E.5 End points

E.5.1

Primary end point(s)

Incidence of women delivering within 7 days post first dose (i.e. within 168 hours of first dose).

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

Time to delivery (from start of investigational medicinal product (IMP) administration until delivery).
Incidence of women delivering within 48 hours post first dose.
Incidence of women delivering before gestational age 37 0/7 weeks.
The progression of uterine contractions from pre-dose to 3 hours, 6 hours and 24 hours post first dose as measured by tocodynamometry.
Maternal plasma concentrations of OBE001 on Day 1 (2 hours post first dose), on Day 2 (pre-dose and 2 hours post-dose), on Day 3 (pre-dose), on Day 7 (post-dose) and at the time of delivery. Umbilical cord plasma concentration of OBE001 at the time of delivery (time matched with maternal sample).

Safety endpoints:
- Maternal incidence of AEs, TEAEs, clinically significant changes in laboratory safety tests, 12-lead ECGs morphology or vital signs from Day 1 until 28 days after birth or term whichever is later.
- Incidence of foetal distress as determined by clinically significant changes in growth retardation and/or foetal heart rate monitoring and/or AFI from Day 1 to Day 14 or birth, whichever is earlier.
- Incidence of infants experiencing adverse events assessed by vital signs, temperature, APGAR score, weight and head circumference at birth as well as measures of neonatal morbidity from birth until 28 days after birth or term whichever is later.
- Incidence of infants with one or more Ages and Stages Questionnaire-3 domain score(s) cut below the cut-off score at 6, 12 and 24 months, adjusted for gestational age.

E.5.2.1

Timepoint(s) of evaluation of this end point

At the time of the interim analysis (when 60 randomised subjects will have either completed the study day 14 and/or have terminated the study and/or have been withdrawn early) and at the end of the study.

In addition, the DMC will review safety data as soon as the first 30 randomised subjects will have either completed study day 14 and/or have terminated the study and/or have been withdrawn early.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

For administrative and safety reporting purposes the end of the study will be defined as the date of the final clinical database lock.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

100

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Subjects and their partners will be invited to participate in a 2 year, observational, safety follow-up of their infants as an extension of the main study.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-03-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-05-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-10-28

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