Clinical Trials Register

Summary
EudraCT Number:	2012-003006-27
Sponsor's Protocol Code Number:	GEXGP24201
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-01-09
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

Germany - BfArM

A.2

EudraCT number

2012-003006-27

A.3

Full title of the trial

A Phase II, Multicentre, Multinational, Randomised, Assessor-Blind Trial to Investigate the Efficacy and Safety of Various Dosages of FSH-GEX™ in Comparison With 150 IU Gonal-f® in Women Undergoing ICSI Treatment

A.3.1

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

Study to evaluate and compare the efficacy and safety of various doses of FSH-GEX with an accepted comparator in women undergoing intracytoplasmatic sperm injection (ICSI) as part of assisted reproduction

A.4.1

Sponsor's protocol code number

GEXGP24201

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	Glycotope GmbH
B.1.3.4	Country	Germany
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	Glycotope GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Glycotope GmbH
B.5.2	Functional name of contact point	Reception
B.5.3	Address:
B.5.3.1	Street Address	Robert-Rössle-Str. 10
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13125
B.5.3.4	Country	Germany
B.5.4	Telephone number	+493094892600
B.5.5	Fax number	+493094892612
B.5.6	E-mail	Trials@glycotope.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	FSH-GEX™
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	FSH
D.3.9.2	Current sponsor code	FSH-GEX™
D.3.9.3	Other descriptive name	RECOMBINANT HUMAN FOLLICLE STIMULATING HORMONE
D.3.9.4	EV Substance Code	SUB20677
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	750
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	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 75 I.E. (5,5 Mikrogramm) Pulver und Lösungsmittel zur Herstellung einer Injektionslösung
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Serono Europe Limited
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.3.4	Pharmaceutical form	Powder and solution for 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	Follitropin alfa
D.3.9.3	Other descriptive name	RECOMBINANT HUMAN FOLLICLE STIMULATING HORMONE
D.3.9.4	EV Substance Code	SUB20677
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	75
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	No

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

women undergoing intracytoplasmatic sperm injection (ICSI) as part of assisted reproduction

E.1.1.1

Medical condition in easily understood language

women having difficulties in becoming pregnant and who are undergoing intracytoplasmatic sperm injection (ICSI) as part of assisted reproduction

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	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10016398
E.1.2	Term	Female infertility
E.1.2	System Organ Class	100000004872

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is the determination of the recommended standard treatment dose of FSH-GEX™ as assessed by follicle growth dynamics in women between 18 and 37 years of age undergoing intracytoplasmic sperm injection (ICSI) treatment.

E.2.2

Secondary objectives of the trial

Secondary objectives are as follows:
1. To compare the efficacy of the different FSH-GEX treatment arms and Gonal-f.
2. To compare the safety and tolerability of the FSH-GEX treatment arms and Gonal-f.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Female patient for whom ICSI treatment is justified at the investigator`s discretion and who is willing to undergo ICSI treatment using ejaculated sperm.
2. Aged 18 – 37 years at Screening.
3. Serum follicle-stimulating hormone (FSH) concentration ≤ 12 IU/l measured between Day 1 and Day 5 of a spontaneous menstrual cycle. Measured within six months before randomisation.
4. Anti-mullerian hormone (AMH): 1 - 4 ng/ml. Measured within six months before randomisation.
5. Antral follicle count (sum of both ovaries): ≥ 7 and ≤ 20.
6. Body mass index (BMI) 18.5-30 kg/m² and body weight ≥ 45 kg and ≤ 90 kg.
7. Presence of both ovaries.
8. Regular spontaneous cycles between 21 and 35 days in length (intercycle variations not more than ± 5 days).
9. Normal uterine cavity as assessed by transvaginal sonography at Screening. No fibroids as assessed by the investigator that would require treatment to facilitate pregnancy.
10. Willing and able to comply with the protocol.
11. Willing and able to provide written informed consent

E.4

Principal exclusion criteria

1. Patients who had more than two unsuccessful previous assisted reproduction technology (ART) cycles (IVF or ICSI) before inclusion into the study, where unsuccessful is defined as no embryo transfer or no biochemical or clinical pregnancy was achieved.
2. Previous poor responders: < 3 oocytes retrieved in previous treatment cycles.
3. Patients with previous hyperstimulation syndrome or cycle cancellation because of imminent hyperstimulation syndrome.
4. Patients with a history of or current polycystic ovarian morphology (PCO) syndrome) according to the Rotterdam consensus criteria
5. Patients with a history of or current endometriosis III or IV according to the American Society for Reproductive Medicine (ASRM) criteria (ASRM, 1996).
6. Presence of ovarian cyst at Screening.
7. Any contraindication to becoming pregnant.
8. History of ≥ 3 clinical or preclinical (absence of gestational sac) miscarriages.
9. An abnormal cervical smear (Papanicolaou [PAP] score ≥ 3, obtained within one year prior to randomisation).
10. Any history of malignant cancer other than in situ breast or skin cancer requiring local excision.
11. Any endocrine abnormalities requiring treatment (latent hypothyroidism treated by thyroxin is allowed).
12. Any clinically significant systematic disease, including history of hormonal abnormalities (e.g. Cushing’s syndrome or androgen producing tumours).
13. Any known infection with human immunodeficiency virus (HIV), hepatitis B or C.
14. History of thrombosis or other risk factors including any coagulation abnormality leading to an increased risk of clotting.
15. Family history of genetic risk factors concerning pregnancy or birth.
16. Use of concomitant medication, which in the opinion of the investigator might interfere with ICSI preparation procedures.
17. Active smoking (no smoking at all allowed) up to four weeks before enrolment in the trial.
18. Any active substance abuse of drugs, medications or alcohol within the last five years.
19. Patients in an institution by official or court order.
20. Patients who are unable or unwilling to provide informed consent.
21. Any participation in another clinical trial within the last 60 days before randomisation.
22. Previous FSH-GEX™ administration.
23. Known hypersensitivity to any component of the investigational and non investigational products used in this study.

E.5 End points

E.5.1

Primary end point(s)

The number of follicles with a diameter of ≥ 12 mm on the day of hCG injection or the day before, after stimulation with FSH-GEX™ compared with Gonal-f®.

E.5.1.1

Timepoint(s) of evaluation of this end point

on the day of hCG injection or the day before

E.5.2

Secondary end point(s)

Secondary efficacy endpoints:
• Follicular response: for each ovary the number of follicles will be classified and summarised as follows: mean diameter 8.0 – 9.9 mm, 10.0 – 11.9 mm, 12.0 – 13.9 mm, 14.0 – 15.9 mm, 16.0 – 17.9 mm, 18.0 – 19.9 mm and larger 19.9 mm
• The number of retrieved cumulus-oocyte-complexes (COCs)
• The number of oocytes retrieved (metaphase II)
• The number of 2PN oocytes one day after follicle puncture
• The rate of biochemical pregnancy and the clinical pregnancy (defined as gestational sac with heartbeat) per randomised patient/puncture/embryo transfer
• Implantation rate (number of foetal sacs on sonography divided by number of embryos transferred per embryo transfer)
• Number of doses and total dose of follicle-stimulating hormone (FSH)
• Pharmacokinetic data for exposure-response relationship exploration
• Pharmacodynamic effect of FSH-GEX™ on E2-estradiol (E2), inhibin B
• Post-study observation: ongoing pregnancy rate (>10 weeks of gestation) and live birth rate

E.5.2.1

Timepoint(s) of evaluation of this end point

see protocol

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

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

Yes

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

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-blind

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

E.8.6.2

Trial being conducted completely outside of the EEA

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, followed by an observation period until birth of the last child

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:

240

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

120

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)

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

2013-01-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-07-30

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