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 | No |
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 |
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E.2.3 | Trial contains a sub-study | No |
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). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | 5 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA 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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 32 |