Clinical Trials Register

Summary
EudraCT Number:	2011-002684-25
Sponsor's Protocol Code Number:	BSGPE2
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-03-14
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2011-002684-25

A.3

Full title of the trial

Efficacy and safety of a 4 year pubertal therapy with growth hormone (somatropine Omnitrope) or an aromatase inhibitor (letrozole Femara) or the combination of both in boys with a short predicted height: The OMNIMARA Trial

Efficacité et sécurité d’un traitement de 4 ans, administré pendant la puberté, à base de l’hormone de croissance (Somatropine Omitrope®) ou d’un inhibiteur de l’aromatase (létrozole Femara®) ou de ces deux médicaments administrés ensemble, chez les garçons ayant un pronostic de petite taille.

Étude Omnimara

Effect en veiligheid van een 4 jaar durende behandeling tijdens de puberteit met groeihormoon (Somatropine Omitrope®) of een aromatase inhibitor (letrozole Femara®) of beiden te samen bij jongens met een kleine voorspelde lengte.

De Omnimara studie

A.3.1

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

Does a combination treatment with growth hormone and an aromatase inhibitor improve growth better than each therapy alone when applied for 4 years to boys in early puberty with a short predicted adult height The OMNIMARA Trial

A.3.2

Name or abbreviated title of the trial where available

OMNIMARA

A.4.1

Sponsor's protocol code number

BSGPE2

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	Antwerp University Hospital
B.1.3.4	Country	Belgium
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	Belgian Study Group for Pediatric Endocrinology, vzw-asbl
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	UZ Antwerpen Dept Pediatrics
B.5.2	Functional name of contact point	Prof Raoul Rooman
B.5.3	Address:
B.5.3.1	Street Address	Wilrijkstraat 10
B.5.3.2	Town/ city	Edegem
B.5.3.3	Post code	2650
B.5.3.4	Country	Belgium
B.5.4	Telephone number	323821 4009
B.5.5	Fax number	323829 1194
B.5.6	E-mail	raoul.rooman@uza.be

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	Omnitrope
D.2.1.1.2	Name of the Marketing Authorisation holder	Sandoz GmbH
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	somatropin
D.3.4	Pharmaceutical form	Solution for injection in cartridge
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	SOMATROPIN
D.3.9.1	CAS number	12629-01-5
D.3.9.4	EV Substance Code	SUB10584MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6.67
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	Femara
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharma NV
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	letrozole
D.3.4	Pharmaceutical form	Coated 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	LETROZOLE
D.3.9.1	CAS number	112809-51-5
D.3.9.4	EV Substance Code	SUB08444MIG
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	2.5
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

boys with idiopathic short adult stature defined as a predicted adult height below or equal to 164.0 cm ( -2.5 SDS) without a known cause

E.1.1.1

Medical condition in easily understood language

boys with a predicted adult height below or equal to 164.0 cm for which no explanation exsists

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10066333
E.1.2	Term	Idiopathic short stature
E.1.2	System Organ Class	100000004859

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 of this study is to test the hypothesis that in boys with a low predicted adult height , adult height gain (height attained minus predicted height) is higher after a 4 year combination therapy with GH (Omnitrope ®) and the aromatase inhibitor letrozole (Femara ®), started at the beginning of puberty, than in patients that receive only GH or only letrozole.

E.2.2

Secondary objectives of the trial

To test for each treatment modality the hypothesis that adult height, attained after the 4 years of therapy, is different from the predicted adult height at the start of the study.
To monitor the safety of the different treatment modalities
To determine the predictors of adult height gain.
the level of aggression during treatment is not different between the treatment groups.
quality of life (Qolissy questionnaire) will improve in all treated groups from the start to the end of the treatment period.
bone mineral density at final height is not different between the treatment groups
bone geometry at final height is not different between the treatment groups.
LH and FSH at final height are not different between the treatment groups.
body composition is not different between the treatment groups
insulin sensitivity at the end of the treatment period is not different between the treatment groups.
To test that the response to letrozole is not dependent on the aromatase polymorphism

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

o Male gender
o Adult height prediction below or equal to –2.5 SD = 164.0 cm based on the vlaamse groeicurve 2004 (vub.ac.be/groeicurven) using the Greulich and Pyle Bayley Pinneau prediction method
o Pubertal: at least 4 ml of testicular volume for boys
o Bone age ≥ 11 but ≤ 13 years
o Signed informed consent

E.4

Principal exclusion criteria

o Children for whom birth length, birth weigth, or parental height are not known
o Bone dysplasia or sitting height/ total height > 2 SDS on standards by Gerver et al (see appendix)
o Vertebral anomalies on spine X ray
o Chronic use of glucocorticoids (including intranasal or intrabronchial glucocorticoid use for more than 90 days in the previous year)
o Previous growth promoting therapy such as GH, sex steroids, oxandrolone, aromatase inhibitors
o Known GH deficiency
o Chronic infectious disease
o Active rheumatic disease
o Previously diagnosed or currently suspected malignancy
o Sex steroid therapy
o Diabetes mellitus
o Renal insufficiency (serum creatinine > 1.5 mg/dl)
o Hepatic disease ( liver test > 3 fold upper limit of normality)
o Current congestive heart failure
o Treatment with a non registered drug during the last 90 days before the moment of inclusion.
o Inability or unwillingness to follow the protocol (measurements, questionnaire)

E.5 End points

E.5.1

Primary end point(s)

adult height gain defined as attained final height minus adult height predicted at the start of the trial

E.5.1.1

Timepoint(s) of evaluation of this end point

Adult height gain is determined when adult height is attained. Adult height is defined as the standing height attained at a bone age of 18.0 years or more in boys.

E.5.2

Secondary end point(s)

1. level of aggression by questionnaire
2. bone geometry
3.quality of life by questionnaire
4.insulin sensitivity
5.bone mineral density

E.5.2.1

Timepoint(s) of evaluation of this end point

1. questionnaire at start, 12 months, at the end of the treatment period ( 48 months) and 12 after the end of treatment
2. pQCT at start, 24 months, at end of treatment and at final height
3. questionnaire at start and at the end of treatment
4. at the end of the treatment period (48 months)
5.DEXA scan at start, end of treatment and at final height

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

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

Yes

E.7.1.3.1

Other trial type description

Investigator Initiated Trial ('Therapeutic confrimatory (Phase III))

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

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)

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

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

when the last subject in the trial has attained his adult height, defined as standing height with a bone age of at least 18 years.

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

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)

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

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)

Trial includes the follow-up of the participants to final height, approximately 3-4 years

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

2012-04-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-08-06

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

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