Clinical Trials Register

Summary
EudraCT Number:	2007-003850-26
Sponsor's Protocol Code Number:	P070303
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2007-08-16
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

France - ANSM

A.2

EudraCT number

2007-003850-26

A.3

Full title of the trial

Etude des effets métaboliques et staturaux de deux modes de traitement par hormone de croissance recombinante des enfants nés petits pour l'âge gestationnel avec déficit statural persistant. Pharmacogénomique de la réponse métabolique et staturale de l'hormone de croissance

A.3.2

Name or abbreviated title of the trial where available

SGA

A.4.1

Sponsor's protocol code number

P070303

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
B.1.3.4	Country	France
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Yes
D.2.1.1.1	Trade name	Norditropine Simplexx 5mg/1.5ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratoires NOVO NORDISK Pharmaceutique S.A.
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Norditropine Simplexx 5mg/1.5ml
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Somatropine
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	5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.2.1.1.1	Trade name	Norditropine Simplexx 10mg/1.5ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratoires NOVO NORDISK Pharmaceutique S.A.
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Norditropine Simplexx 10mg/1.5ml
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	somatropine
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	10
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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	Yes
D.2.1.1.1	Trade name	Norditropine Simplexx 15mg/1.5ml
D.2.1.1.2	Name of the Marketing Authorisation holder	Laboratoires NOVO NORDISK Pharmaceutique S.A.
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Norditropine Simplexx 15mg/1.5ml
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Somatropine
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	15
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

Enfant né Petit pour l'Age Gestionnel traités par rhGH

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.1
E.1.2	Level	PT
E.1.2	Classification code	10053759
E.1.2	Term	Growth retardation

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Identifier, décrire et analyser les facteurs responsables des variations individuelles de la réponse à un traitement par l'hormone de croissance recombinante humaine (rhGH) -croissance, métabolisme et sensibilité à l'insuline - des enfants de petite taille nés petits pour l'âge gestationnel (PTAG).

E.2.2

Secondary objectives of the trial

1. Etudier les effets métaboliques du traitement par rhGH, en analysant particulièrement l'effet sur la lipolyse et la sensibilité à l'insuline.
2. Analyser la croissance des ces enfants traités par rhGH.
3. Déterminer si les effets métaboliques de l'hormone de croissance sont corrélés à l'effet statural ;
4. Identifier les facteurs, en particulier génétiques, impliqués dans la variation individuelle de la réponse au traitement par rhGH.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Enfant né PTAG permettant un traitement par hormone de croissance dans le cadre des conditions de mise sous traitement autorisant le remboursement par la sécurité sociale.
- Consentement éclairé des parents
- Taille de naissance < -2 DS pour l'âge gestationnel
- Taille < -3 DS à l'inclusion, selon les critères de l'AMM de la Norditropine® Simplexx® en France
- Vitesse de croissance < 0.0 DS au cours de la dernière année
- Taille parentale ajustée < -1 DS ;
- Filles âgées de 4 à 9 ans (inclus) et garçons de 4 à 10 ans (inclus) ;
- L'enfant et ses parents doivent être volontaires et capables de comprendre toutes les étapes de l'étude ;
- L'enfant ne doit pas avoir reçu de traitement par hormone de croissance avant l'inclusion ;
- Absence de déficit en hormone de croissance affirmé par une valeur d'hormone de croissance supérieure à 20 mUI/l au cours d'un test de stimulation de l'hormone de croissance ;
- Absence de développement pubertaire : volume testiculaire inférieur à 4 ml pour les garçons et absence de développement des seins pour les filles.

E.4

Principal exclusion criteria

- Allergie au produit de l'étude
- Traitement par hormone de croissance avant l'étude ;
- Déficit en hormone de croissance, IGF-I ou autre déficit hypophysaire ;
- Causes connues de petites tailles comprenant, mais non limitées, aux anomalies chromosomiques ;
- Processus tumoral connu et évolutif ;
- Traitement en cours par des substances connues pour altérer la croissance (type corticoïdes) ;
- Retard mental sévère (jugé par l'investigateur) ;
- Cardiopathie hypertrophique;
- Hypertension artérielle non contrôlée;
- Hypertension intracrânienne bénigne;
- Intolérance au glucose, diabète ou dyslipidémie connus ;
- Hépatite aigue ou chronique active ;
- Insuffisance rénale chronique ;
- Anomalies chromosomiques et /ou syndromes génétiques (autres que le syndrome de Silver-Rusell).
- Non affiliation à un régime de sécurité sociale
- Hypersensibilité à l'un des excipients du produit ;
- En cas d'antécédent de tumeur cérébrale, tout traitement antitumoral devra être terminé et les lésions intracrâniennes stabilisées avant de commencer le traitement ;
- Les patients présentant un état critique aigu, souffrant de complications secondaires à une intervention chirurgicale à coeur ouvert, une intervention chirurgicale abdominale, un polytraumatisme accidentel, une insuffisance respiratoire aigue ou à une situation similaire ne doivent pas être traités par Norditropine.

E.5 End points

E.5.1

Primary end point(s)

Evaluation de la réponse métabolique (tolérance) et de la croissance (efficacité du mode de traitement : un groupe à dose constante et un groupe dont le traitement est adapté au taux d'IGF-I sérique)
L'évaluation de la croissance avant, et pendant le traitement par rhGH sera basée sur l'analyse de paramètres cliniques, biologiques et radiologiques :
Le profil métabolique de chaque patient sera établi selon des critères cliniques et biologiques.

Evaluation de la relation entre l'effet de l'hormone de croissance et la variation allélique des gènes (Etude en cours à l'hôpital Saint Vincent de Paul)

Evaluation de la réponse cellulaire de l'hormone de croissance sera faite sur des lymphocytes CD4+. La relation entre un phénotype et la réponse moléculaire à l'hormone de croissance (protéome, transcriptome) sera analysé

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

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

Yes

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)

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

2 modes de traitement

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

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

Information not present in EudraCT

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

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	Yes
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	Yes
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	No
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	Information not present in EudraCT
F.3.3.2	Women of child-bearing potential using contraception	Information not present in EudraCT
F.3.3.3	Pregnant women	Information not present in EudraCT
F.3.3.4	Nursing women	Information not present in EudraCT
F.3.3.5	Emergency situation	Information not present in EudraCT
F.3.3.6	Subjects incapable of giving consent personally	Information not present in EudraCT
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	100

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

2007-10-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-10-09

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

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