Clinical Trials Register

Summary
EudraCT Number:	2017-002579-25
Sponsor's Protocol Code Number:	17-OBE022-003
National Competent Authority:	Finland - Fimea
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-08-11
Trial 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

Finland - Fimea

A.2

EudraCT number

2017-002579-25

A.3

Full title of the trial

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

A.3.1

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

OBE022 added-on to atosiban in threatened spontaneous preterm labour, Proof of Concept study

A.3.2

Name or abbreviated title of the trial where available

PROLONG

A.4.1

Sponsor's protocol code number

17-OBE022-003

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 Trial Director
B.5.3	Address:
B.5.3.1	Street Address	12, Chemin des Aulx
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	410225523840
B.5.5	Fax number	41022743 29 21
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	OBE022
D.3.2	Product code	OBE022
D.3.4	Pharmaceutical form	Granules for oral suspension
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	2005486-32-6
D.3.9.2	Current sponsor code	OBE022
D.3.9.3	Other descriptive name	OBE022
D.3.9.4	EV Substance Code	SUB182291
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	500
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	Granules for oral suspension
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

oral treatment of threatened spontaneous preterm labour in weeks 24 to 34 of pregnancy

E.1.1.1

Medical condition in easily understood language

to delay imminent preterm birth in pregnant women

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10075863
E.1.2	Term	Preterm labor
E.1.2	System Organ Class	100000004868

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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

E.5 End points

E.5.1

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 birth.
• 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.

PK Endpoint:
• Plasma concentration of OBE022/OBE002 at Day 1, Day 2, Day 3 and Day 7.
• Pharmacokinetic parameters of OBE022/OBE002 at Day 7: AUC, Cmax and half-life.
• Fœtal (cord blood)-maternal exposure ratio at the time of delivery for patients who received IMP treatment within the previous 24 h.

PD Endpoint:
• Uterine contractions at each hour during the first 6 hours after IMP start.

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy, PK and PD:
When the last patient has completed the 28 Day visit after Day of delivery

Safety (Infant Follow-up):
when the last infant has completed 24 month follow-up

(Preliminary and interim analyses
Part A
Preliminary safety and PK analyses in Part A will be conducted after 4 and 8 patients have either reached Day 7 of the Treatment Phase or terminated the study.
Part B
A first interim analysis will be conducted after a total of 30 patients have either reached Day 7 of the Treatment Phase or terminated the study. A second interim analysis will be conducted after a total of 60 patients have either reached Day 7 of the Treatment Phase or terminated the study, in order to decide whether to stop or include up to 60 additional patients.)

E.5.2

Secondary end point(s)

Not Applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Czech Republic

Finland

Israel

Poland

Russian Federation

Spain

Vietnam

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

end of the Infant Follow-up.

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:

130

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

Yes

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

F.4.2.2

In the whole clinical trial

130

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)

None

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

2017-10-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-09-21

P. End of Trial
P.	End of Trial Status	Completed

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