Clinical Trials Register

Summary
EudraCT Number:	2014-002254-40
Sponsor's Protocol Code Number:	14-OBE001-013
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-09-19
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

Denmark - DHMA

A.2

EudraCT number

2014-002254-40

A.3

Full title of the trial

A phase 2, double-blind, dose-finding, placebo-controlled study to assess the safety and efficacy of a single oral administration of OBE001 to improve embryo implantation following IVF or ICSI.

A.3.1

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

OBE001 Phase 2 dose-finding study versus placebo in women undergoing embryo transfer in the context of IVF or ICSI.

A.3.2

Name or abbreviated title of the trial where available

IMPLANT

A.4.1

Sponsor's protocol code number

14-OBE001-013

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	Véronique Lecomte
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	OBE001
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.IMP: 2
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	OBE001
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	200
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
D.8 Placebo: 2
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

Embryo implantation in women undergoing embyo transfer following IVF/ICSI in the context of Assisted Reproductive Technology (ART).

E.1.1.1

Medical condition in easily understood language

Embryo implantation in women undergoing embyo transfer following IVF/ICSI in the context of Assisted Reproductive Technology (ART).

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	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10073184
E.1.2	Term	Embryo transfer
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Efficacy objective:
• To assess the efficacy of a range of single oral doses of OBE001 compared to placebo to increase the clinical pregnancy rate defined as a positive embryo heart-beat at 6 weeks post Embroy Transfer (ET) day.

Safety Objective:
• To evaluate the safety and tolerability of OBE001 when administered orally to women undergoing embryo transfer following IVF or ICSI.
• To evaluate infant developmental outcome at 6 months after birth.

Pharmacokinetic- Pharmacodynamic Objective:
• To establish the possible relationship between inhibition of uterine contractions, pregnancy rate and OBE001 plasma levels.

E.2.2

Secondary objectives of the trial

Efficacy Objectives:
• To assess the efficacy of a range of single oral doses of OBE001 compared to placebo on the following:
- to increase the pregnancy rate defined as a positive blood pregnancy test at 14 days post OPU day.
- to increase the on-going pregnancy rate defined as a positive embryo heart-beat at 10 weeks post OPU day.
- to increase the embryo-implantation rate defined as the number of intra-uterine embryos with positive heart-beat at 6 weeks post ET day divided by the number of embryos transferred.
- to decrease the rate of uterine contractions (UC/min) prior to embryo transfer.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. The Subject must provide written informed consent prior to initiation of any study related procedures, as shown by a signature on the volunteer consent form.
2. The Subject must be a healthy female volunteer aged from 18 years to 36 years inclusive at screening.
3. The Subject must be medically indicated for IVF/ICSI in the context of ART.
4. The Subject must have undergone not more than 1 previous IVF or ICSI cycle that resulted in a negative βhCG test, despite transfer of at least one embryo/blastocyst of good quality during the cycle (but not counting any attempts before a prior pregnancy).
5. The Subject must in the current COH cycle for IVF/ICSI follow a GnRH antagonist protocol with or without pre-treatment with an oral contraceptive pill.
6. The Subject must in the current COH cycle for IVF/ICSI receive a single injection of hCG for triggering final follicular maturation.
7. The Subject must in the current COH cycle for IVF/ICSI receive a luteal phase support with vaginal micronized progesterone at 600 mg per day (3 × 200 mg) beginning either on the day of oocyte retrieval or on the day after oocyte retrieval. Alternatively, the use of vaginal micronized progesterone tablets is allowed at 300 mg per day (3 x 100 mg) according to the approved product label for Lutinus/Endometrin 100 mg vaginal tablets.
8. The Subject must undergo oocyte retrieval for IVF/ICSI for the purpose of fresh transfer on day 3 post-Oocyte Pick-Up day (OPU day + 3 days).
9. The Subject must have had at least 4 mature oocytes picked-up in the preceding COH cycle, if any.
10. The Subject must have at least 4 mature oocytes picked-up in the current COH cycle.
11. The Subject must have at least one good quality embryo in the current COH cycle being defined as having six to eight blastomeres of uniform size and shape at Day 3, ooplasm having no granularity, absence of multinucleation and a maximum fragmentation of 10%.
12. The Subject must present evidence of uterine contractions on transvaginal ultrasound video at baseline (prior to OBE001/placebo administration).
13. The Subject must have at least 1 functional ovary.
14. The Subject must have a BMI ≥ 18 kg/m2 and ≤ 35 kg/m2.
15. The Subject must be able to communicate well with the investigator and research staff and to comply with the requirements of the study protocol.

E.4

Principal exclusion criteria

1. The Subject is programmed for a transfer of 3 or more embryos in the current COH cycle.
2. The Subject is programmed for a blastocyst stage transfer in the current COH cycle.
3. The Subject undergo a frozen-thaw embryo transfer in the current COH cycle.
4. The Subject’s partner is requiring a surgical testicular sperm extraction.
5. The Subject has a known abnormal karyotype.
6. The Subject has a known acquired or congenital thrombophilia disease.
7. The Subject has any condition, including findings in the medical history or in the pre-trial assessments, 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.
8. The Subject has any clinically significant abnormality in the results of the screening safety laboratory tests, including AST, ALT, GGT, alkaline phosphatase or total bilirubin above twice upper limit of normal. In case of isolated GGT increase, a single re-test is allowed.
9. The Subject has any significant abnormality relevant to the ART procedure and outcome, in the results of the screening gynaecological examination, which in the opinion of the PI could interfere with the trial objectives, conduct or evaluation (e.g. significant uterine anomaly or hydrosalpinges documented during screening ultrasound).
10. The Subject has a known severe endometriosis (stage III or IV) and/or adenomyosis.
11. The Subject is at risk of severe Ovarian Hyper Stimulation Syndrome (OHSS).
12. The Subject has any clinically significant abnormality on the 12-lead ECG recording at screening.
13. The Subject has any clinically significant abnormality on arterial blood pressure (BP) or heart rate (HR) at screening.
14. The Subject has a known positive results from virology tests for hepatitis B surface antigen (HBsAg) (not due to vaccination), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) 1 or 2.
15. The Subject is prone to frequent, severe hypersensitivity to drugs, in particular with chemical structure similar to OBE001.
16. The Subject has been administered with any experimental drug in the 12 weeks before dosing.
17. The Subject has forfeit her freedom by administrative or legal award or who was under guardianship.
18. The Subject is likely to require treatment with drugs that are not permitted during the study from the day of hCG single injection up to the study visit V3 (OPU day + 14 days) such as:
• Drugs with utero-relaxant properties: Ca channel blockers, beta-sympathomimetic agents, nitroglycerine, magnesium sulfate (MgSO4), potassium channel openers, NSAIDs, drugs for functional GI disorders
• Drugs with utero-tonic properties: Dopamine, progesterone antagonists, prostaglandin analogues
• triptins and ergotamines
19. The Subject has a history of, or known current (within twelve months) problems with alcohol or drug abuse.
20. The Subject has participated in any previous studies involving oxytocin receptor antagonists during this and any previous ART cycles.

E.5 End points

E.5.1

Primary end point(s)

Efficacy endpoint:
• Percentage of women with an intra-uterine pregnancy with positive embryo heart-beat at 6 weeks post ET day.

Safety endpoints:
• Treatment emergent adverse events frequency and severity (until the End-of-Study visit).
• Haematology and biochemistry assessments at screening (prior to OBE001/placebo administration) and at visit V3 (14 days post OPU day).
• Incidence of infants with one or more Ages and Stages Questionnaire-3 domain score(s) below the cutoff score at 6 months, adjusted for gestational age at birth.

Pharmacokinetic-Pharmacodynamic endpoints:
• Plasma levels of OBE001 (pre-dose and at the time of embryo transfer).
• Uterine contractions relationship to OBE001 plasma levels and pregnancy rate, with possible covariates of serum E2 and P4 levels and uterine contractions at baseline.

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy endpoint
At the time af the Interim analysis (will be performed when 120 randomised subjects will have either completed the study visit V4 and/or have terminated the study and/or have been early withdrawn) and at end of the study.
Pharmacokinetic-Pharmacodynamic endpionts:
• At the end of the study

Safety endpoints:
• Throughout the study for the safety endpoints.
• At 6 months after birth, adjusted for gestational age at birth.

E.5.2

Secondary end point(s)

Efficacy endpoints:
• Percentage of women with positive blood pregnancy test at 14 days post OPU day.
• Percentage of women with an intra-uterine pregnancy with positive embryo heart-beat at 10 weeks post OPU day.
• The embryo-implantation rate defined as the number of intra-uterine embryos with positive heart-beat at 6 weeks post ET day divided by the number of embryos transferred.
• Change (absolute and relative) from baseline (prior to OBE001/placebo administration) to the time of ET (about 3.5 hours after OBE001/placebo administration and prior to ET) in the rate of uterine contractions (UC/min).

E.5.2.1

Timepoint(s) of evaluation of this end point

- At the end of the study

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

Yes

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 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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

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:

240

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

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

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

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

Information not present in EudraCT

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

240

F.4.2.2

In the whole clinical trial

240

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)

Post-study data on the pregnancy and birth (i.e. key information on the gestation and on the delivery outcome) and on the condition of the newborn at birth and during at least 28 days post delivery (i.e. birth weight and height, presence of any malformation at birth and occurance of any significant morbidity during the neo-natal period) will be collected.
In addition, Data from the Age and Stages questionnaire (ASQ-3) at 6 months after birth will be collected.

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

2014-11-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-11-29

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