Clinical Trials Register

Summary
EudraCT Number:	2014-005331-14
Sponsor's Protocol Code Number:	1411-MAD-079-CB
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-03-11
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

Spain - AEMPS

A.2

EudraCT number

2014-005331-14

A.3

Full title of the trial

A prospective randomized trial to analyze the effect of the gonadotropin administered during controlled ovarian stimulation on embryo kinetics of development

Efecto del tipo de gonadotropina empleada en la estimulación ovárica sobre la cinética de desarrollo embrionaria

A.3.1

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

Type of gonadotropin and embryo kinetics of development

Tipo de gonadotropina y cinética del desarrollo embrionario

A.3.2

Name or abbreviated title of the trial where available

Type of gonadotropin and embryo kinetics of development

Tipo de gonadotropina y cinética del desarrollo embrionario

A.4.1

Sponsor's protocol code number

1411-MAD-079-CB

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	IVI Madrid
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	IVI Madrid
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IVI Madrid
B.5.2	Functional name of contact point	IVI Madrid
B.5.3	Address:
B.5.3.1	Street Address	Avda del Talgo 68-70
B.5.3.2	Town/ city	Madrid-Aravaca
B.5.3.3	Post code	28023
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34911802900
B.5.5	Fax number	+34911802909
B.5.6	E-mail	Carmen.Bou@ivi.es

D. IMP Identification
D.IMP: 1
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	Elonva
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Limited
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subdermal use (Noncurrent) Subconjunctival use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CORIFOLLITROPIN ALFA
D.3.9.1	CAS number	195962-23-3
D.3.9.4	EV Substance Code	SUB01455MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	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	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	Puregon
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Limited
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Suspension for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Skin scarification Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FOLLITROPIN BETA
D.3.9.3	Other descriptive name	FOLLITROPIN BETA
D.3.9.4	EV Substance Code	SUB12503MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
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	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: 3
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	Menopur
D.2.1.1.2	Name of the Marketing Authorisation holder	Ferring S.A.U
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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 solvent for solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subconjunctival use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	HUMAN MENOPAUSAL GONADOTROPHINS
D.3.9.1	CAS number	61489-71-2
D.3.9.3	Other descriptive name	HUMAN MENOPAUSAL GONADOTROPHINS
D.3.9.4	EV Substance Code	SUB22171
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

The study is proposed to analyze the effect of three types of gonadotropin on embryo quality and kinetics of development in women undergoing an assisted reporduction treatment

El estudio propone analizar el efecto de tres tipos de gonadotropinas sobre la calidad y cinética embrionaria en mujeres que se someten a un tratamiento de Reproducción Asistida.

E.1.1.1

Medical condition in easily understood language

It is intended to determine the effect of controlled ovarian stimulation on embryo quality, according the timings of cellular divisions

Se propone determinar el efecto de un protocolo de estimulación ovárica sobre la calidad embrionaria, en términos de tiempos de división celular

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Non-inferiority study of the type of gonadotropin used during a controlled ovarian stimulation protocol.
To compare if the gonadotropin administered during ovarian stimulation affects timing of embryo divisions until 5 cell-stage

Estudio de no inferioridad del tipo de gonadotropina empleado en un protocolo de estimulación ovárica
Determinar si los preparados gonadotrópicos empleados en la estimulación ovárica (FSH recombinante, HMG y corifolitropina alfa) afectan a los tiempos de división celular hasta 5 células

E.2.2

Secondary objectives of the trial

To prove if the dose of gonadotropin applied and the serum steroid levels the day of the triggering (estradiol and progesterone) affects embryo quality and development rate using time-lapse technology

Comparative analysis of fertilization, pregnancy and implantation rates

Comprobar si las dosis de gonadotropinas aplicadas y los niveles de hormonas esteroideas en sangre (estradiol y progesterona) el día de la inducción de la ovulación condicionan la calidad y tasa de desarrollo embrionario mediante el uso de tecnología time-lapse.

Análisis comparativo de las tasas de fecundación, tasas de gestación y tasas de implantación.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Women <38 years old
Weight <60 kg
Own oocytes
Patients have to provide signed informed consent

Pacientes menores de 38 años
Peso <60 kg
Ovocitos propios
Paciente que otorgue por escrito su consentimiento para participar en el Estudio

E.4

Principal exclusion criteria

Oocyte donors
Vitrified oocytes
Severe male factor (<1 million spz/ml)
Weight >60 kg

donantes de ovocitos
ovocitos vitrificados
factor masculino severo (recuento espermático < 1.106 espermatozoides/ml)
Pesar >60 Kg.

E.5 End points

E.5.1

Primary end point(s)

T5 defined as the time that embryo needs to reach a 5-cell stage

T5, definida como el tiempo que necesita el embrión para alcanzar un estadio de 5-células

E.5.1.1

Timepoint(s) of evaluation of this end point

In real time

En tiempo real

E.5.2

Secondary end point(s)

Length of stimulation (days)
- Total dose of gonadotropins (IU)
- Levels of FSH (IU)
- Levels of estradiol (pg / ml)
- Levels of progesterone (ng / ml)
- Fertilization rate
- Number of embryos transferred and cryopreserved
- Pregnancy rate
- Implantation rate
- Miscarriage rate
- Cancellation rate per cycle initiated
- Ovarian hyperstimulation síndrome rate
- Timings of cellular divisions

duración del tratamiento (días de estimulación)
- dosis total de gonadotropinas
- niveles de FSH (UI)
- niveles de estradiol (pg/ml)
- niveles de progesterona (ng/ml)
- tasa de fecundación
- número de embriones transferidos y criopreservados
- tasa de gestación
- tasa de implantación
- tasa de aborto
- tasa de cancelación por ciclo iniciado
- tasa de síndrome de hiper-estimulación ovárica.
- tiempos de las divisiones celulares

E.5.2.1

Timepoint(s) of evaluation of this end point

A month

1 mes

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

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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)

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

The test will be terminated when each patient has completed the
follow-up period, or by discontinuation by:
- Completion of the assay protocol
- Loss of tracking (inability to contact the patient)
- Decision of the patient (specify reason)
- Decision of the researcher (gynecologist or nurse)
- Preventing adverse reaction by continuing the patient in the trial
- Death

El ensayo se dará por finalizado cuando cada paciente haya concluido el
periodo de seguimiento, o bien por interrupción del mismo por:
- Finalización del ensayo por protocolo
- Pérdida de seguimiento (incapacidad de contactar con la paciente)
- Decisión de la paciente (especificar el motivo)
- Decisión del investigador (ginecólogo o personal de enfermería)
- Por reacción adversa que impida la continuación de la paciente en
el ensayo
-Fallecimiento

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

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:

200

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

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

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

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

200

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

Ninguno

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

2015-08-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-09

P. End of Trial
P.	End of Trial Status	Ongoing

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