Clinical Trials Register

Summary
EudraCT Number:	2013-001669-17
Sponsor's Protocol Code Number:	000004
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:	2013-08-07
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

2013-001669-17

A.3

Full title of the trial

A randomised, controlled, assessor-blind, parallel groups, multicentre, multinational trial comparing the efficacy and safety of FE 999049 with follitropin alfa (GONAL-F) in controlled ovarian stimulation in women undergoing an assisted reproductive technology programme

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

ESTHER-1

A.4.1

Sponsor's protocol code number

000004

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	Ferring Pharmaceuticals A/S
B.1.3.4	Country	Denmark
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	Ferring Pharmaceuticals A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ferring Pharmaceuticals A/S
B.5.2	Functional name of contact point	Clinical Development Support
B.5.3	Address:
B.5.3.1	Street Address	Kay Fiskers Plads 11
B.5.3.2	Town/ city	Copenhagen S
B.5.3.3	Post code	2300
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+452878 76 25
B.5.5	Fax number	+45 8833 88 80
B.5.6	E-mail	DK0-Disclosure@ferring.com

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	FE 999049
D.3.2	Product code	FE 999049
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FE 999049
D.3.9.2	Current sponsor code	FE 999049
D.3.9.3	Other descriptive name	human recombinant follicle-stimulating hormone
D.3.9.4	EV Substance Code	SUB121093
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	33.3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
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	Comparator
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	Yes
D.2.1.1.1	Trade name	GONAL-F
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Serono Europe Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	GONAL-F 900 IU/1.5 ml (66 micrograms/1.5 ml) solution for injection in pre-filled pen
D.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FOLLITROPIN ALFA
D.3.9.1	CAS number	56832-30-5
D.3.9.3	Other descriptive name	FOLLITROPIN ALFA
D.3.9.4	EV Substance Code	SUB12426MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	600
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Pre-filled pen with multidose cartridge

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Infertility

E.1.1.1

Medical condition in easily understood language

A new recombinant FSH (follicle-stimulating hormone) compound intended to induce development of multiple egg sacs in women undergoing ovarian stimulation as part of infertility treatment

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10021926
E.1.2	Term	Infertility
E.1.2	System Organ Class	10038604 - Reproductive system and breast disorders

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 demonstrate non-inferiority of FE 999049 compared with GONAL-F with respect to ongoing pregnancy rate and ongoing implantation rate in the fresh cycle in women undergoing controlled ovarian stimulation

E.2.2

Secondary objectives of the trial

To compare the clinical benefits of FE 999049 in its dosing regimen to those of GONAL-F with respect to efficacy and safety
To compare FE 999049 with GONAL-F with respect to ovarian response including follicular development and endocrine profile, as well as with respect to embryo development
To compare FE 999049 with GONAL-F with respect to treatment efficiency
To compare FE 999049 with GONAL-F with respect to safety profile, including adverse events, routine safety laboratory parameters and local tolerability
To evaluate the immunogenicity of FE 999049 after one treatment cycle
To compare FE 999049 with GONAL-F with respect to cost-effectiveness

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

This trial will include women undergoing their first IVF/ICSI cycle and aged 18-40 years. They have been diagnosed with tubal infertility, endometriosis stage I/II or have partners diagnosed with male factor infertility, and are considered eligible for IVF or ICSI. The allowed body mass index (BMI) is 17.5 – 32.0 kg/m2, thus including underweight, normal weight, overweight and obese patients.

E.4

Principal exclusion criteria

Subjects with endometriosis stage III/IV, known history of recurrent miscarriage or with contraindications to controlled ovarian stimulation with gonadotropins will be excluded from participation in this trial.

E.5 End points

E.5.1

Primary end point(s)

1. Ongoing pregnancy rate (at least one intrauterine viable fetus 10-11 weeks after transfer)
2. Ongoing implantation rate (number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocytes transferred)

E.5.1.1

Timepoint(s) of evaluation of this end point

1. 10-11 weeks after transfer
2. 10-11 weeks after transfer

E.5.2

Secondary end point(s)

1. Positive βhCG (positive serum βhCG test 13-15 days after transfer)
2. Clinical pregnancy rate (at least one gestational sac 5-6 weeks after transfer)
3. Vital pregnancy rate (at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer)
4. Implantation rate (number of gestational sacs 5-6 weeks after transfer divided by number of blastocytes transferred)
5. Proportion of subjects with extreme ovarian responses, defined as < 4, ≥ 15 or ≥ 20 oocytes retrieved
6. Proportion of subjects with early OHSS (including OHSS of moderate/severe grade) and/or preventive interventions for early OHSS
7. Proportion of subjects with cycle cancellation due to poor ovarian response or excessive ovarian response
8. Number and size of follicles on stimulation day 6 and end-of-stimulation
9. Percentage of metaphase II oocytes (only applicable for those inseminated using ICSI), fertilization rate as well as number and quality of embryos on day 3 and blastocytes on day 5 after oocyte retrieval
10. Circulating concentrations of FSH, LH, estradiol, progesterone, inhibin A and inhibin B on stimulation day 6 and end-of-stimulation
11. Total gonadotropin dose and number of stimulation days
12. Frequency and intensity of adverse events
13. Changes in circulating levels of clinical chemistry and haematology parameters and proportion of subjects with markedly abnormal changes
14. Frequency and intensity of injection site reactions (redness, pain, itching, swelling and bruising) assessed by subject during the stimulation period

E.5.2.1

Timepoint(s) of evaluation of this end point

1. 13-15 days after transfer
2. 5-6 weeks after transfer
3. 5-6 weeks after transfer
4. 5-6 weeks after transfer
5. Oocyte retrieval visit
6. 9 days after triggering
7. End-of-stimulation
8. Stimulation day 6 and end-of-stimimulation
9. Prior to insemination, culture day 1, culture day 3 and culture day 5
10. Stimulation day 6 and end-of-stimulation
11. End-of-stimulation
12. From signing Informed consent until end-of-trial visit
13. Stimulation day 1, end-of-stimulation and end-of-trial
14. End-of-stimulation

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

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

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Assessor blinded

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

European Union

Brazil

Canada

Mexico

Russian Federation

E.8.7

Trial has a data monitoring committee

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

LVLS in the post-trial follow-up phase of the study

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

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:

1350

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

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

F.4 Planned number of subjects to be included

F.4.1

In the member state

135

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1015

F.4.2.2

In the whole clinical trial

1350

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 who do not become pregnant have the possibility to enter study 000071

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

2013-08-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-09-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-01-03

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