Clinical Trials Register

Summary
EudraCT Number:	2011-005155-14
Sponsor's Protocol Code Number:	PKM11204
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2012-02-06
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2011-005155-14

A.3

Full title of the trial

An open-label, pharmacokinetic, pharmacodynamic, and tolerability study of AVE5026 administered at weight-adjusted doses to patients under 18 years of age with a Central Venous Line (CVL)

Nyílt farmakokinetikai/farmakodinámiás és tolerálhatósági vizsgálat a testsúly szerinti adagokban alkalmazott AVE5026 értékelésére centrális vénás kanüllel rendelkező 18 év alatti betegeknél

A.3.1

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

Study of AVE5026 at weight-adjusted doses in children with a Central
Venous Line

A testsúly szerinti adagolt AVE5026 vizsgálata centrális vénás kanüllel rendelkező gyermekeken

A.4.1

Sponsor's protocol code number

PKM11204

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/029/2012

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	sanofi-aventis Recherche et Développement
B.1.3.4	Country	France
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	sanofi-aventis Recherche & Développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	sanof-aventis Zrt.
B.5.2	Functional name of contact point
B.5.3	Address:
B.5.3.1	Street Address	Tó u. 1-5.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1045
B.5.3.4	Country	Hungary
B.5.6	E-mail	kapcsolat@sanofi.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	Semuloparin sodium
D.3.2	Product code	AVE5026
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	semuloparin sodium
D.3.9.2	Current sponsor code	AVE5026
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	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)	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	Yes
D.3.11.13.1	Other medicinal product type	Controlled Chemical Heparin depolymerisation
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	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	Semuloparin sodium
D.3.2	Product code	AVE5026
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	semuloparin sodium
D.3.9.2	Current sponsor code	AVE5026
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	20
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	Yes
D.3.11.13.1	Other medicinal product type	Controlled Chemical Heparin depolymerisation

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

Prevention of thromboembolism

E.1.1.1

Medical condition in easily understood language

Prevention of thromboembolism

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10043566
E.1.2	Term	Thromboembolism
E.1.2	System Organ Class	10047065 - Vascular 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 assess the pharmacokinetic and pharmacodynamic parameters
of AVE5026 (assessed from the anti-Xa activity of AVE5026) in
children in order to determine the dose to be assessed in the
subsequent clinical efficacy/safety study

E.2.2

Secondary objectives of the trial

To assess the tolerability of AVE5026 when administered at a
weight-adjusted, once daily dose for up to 30 days

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Male and female patient - age between ≥ 38 gestational weeks and < 18 years
Central Venous Line implanted for an expected duration ≥ 6 days from study enrolment
Patient hospitalized or able to receive daily injection for at least 6 days and provide plasma samples at Day 4, 5 and 6 at the pre-specified time points
Written informed consent signed by legal representative(s) in accordance with local regulation, and possibly assent form by the child (country/age specific)

E.4

Principal exclusion criteria

Patient for whom anticoagulant therapy is contraindicated
Planned treatment with other antithrombotic agents within 2 weeks prior to enrolment and during the course of the study
Any previous exposure to AVE5026 (eg. previous enrolment in the current study)
Documented history of heparin-induced thrombocytopenia
Severe thrombocytopenia (platelets < 50 x 10 000 000 000/L)
Active bleeding
Recent (less than 3 weeks prior to enrollment) brain, spinal or ophthalmologic surgery
Uncontrolled hypertension characterized by a sustained systolic pressure or diastolic pressure greater than 2 standard deviations above the age-related norm
Severe hepatic disease (e.i. more than 2.5 times the upper limit for age of hepatic enzymes)
Severe renal insufficiency (estimated creatinine clearance < 30 ml/min using the Schwartz formula)
Any condition that, in the opinion of the Investigator, would expose the patient to an unfavorable risk/benefit ratio
Presence or history of drug hypersensitivity
Any patient currently involved in another clinical trial with an investigational drug according to applicable regulations
Any patient or parent(s)/legal guardian(s) who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development
Any patient or parent(s)/legal guardian(s) who cannot be contacted in case of emergency
Pregnant or breast-feeding female
Female of childbearing potential who are unwilling to abstain from sexual intercourse and therefore are at risk of becoming pregnant and are not protected by highly effective contraceptive method of birth control and/or who are unwilling or unable to be tested for pregnancy

E.5 End points

E.5.1

Primary end point(s)

Pharmacokinetics: Plasma concentrations of AVE5026.
Individual pharmacokinetic parameters of AVE5026 in children will be derived from a full population PK model building (including covariates assessment).

Pharmacodynamic activity (anti-Xa activity) of AVE5026.
Individual pharmacodynamic parameters of AVE5026 in children will be derived from a full population PK/PD model building (including covariates assessment).

E.5.1.1

Timepoint(s) of evaluation of this end point

6 days

E.5.2

Secondary end point(s)

Safety parameters including bleeding
Safety parameters including transfusions requirement
Safety parameters including hemoglobin, platelet count
Safety parameters including liver and renal laboratory data
Safety parameters including serious adverse events
Safety parameters including non-serious adverse events

E.5.2.1

Timepoint(s) of evaluation of this end point

up to 30+/- 2 days post treatment

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

Yes

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

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

E.8.1.1

Randomised

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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.8.4.1

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

Brazil

Canada

Guatemala

Hong Kong

Hungary

Israel

Mexico

Peru

Romania

Russian Federation

Singapore

Slovakia

Spain

Switzerland

Turkey

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

LVLS

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

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

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

Yes

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

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Depending on age and country.
Extract from the protocol: "Inclusion criteria number 4: Written informed consent signed by legal representative(s) in accordance with local regulation, and possibly assent form by the child (country/age specific)."

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)

Not Applicable

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

2012-03-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-08

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2012-06-26

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