E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of thromboembolism |
Prevención de tromboemlismo |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of thromboembolism |
Prevención de tromboemlismo |
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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 |
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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 |
Determinar los parámetros farmacocinéticos y farmacodinámicos de AVE5026 (evaluados a partir de la actividad anti-Xa del compuesto con y sin adición de antitrombina (AT) en el medio reactivo) en niños, para identificar la dosis necesaria para un ensayo de eficacia/seguridad próximo |
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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 |
Evaluar la tolerabilidad de AVE5026 cuando se administra ajustado al peso, una vez al día hasta 30 días |
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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) |
? Edad: entre ? 38 semanas gestacionales y < 18 años ? VVC implantada con una duración prevista de ? 6 días desde la inclusión en el estudio ? Hospitalizado o capaz de recibir inyecciones diarias durante al menos 6 días y capaz de proporcionar muestras de plasma durante 3 días (Día 4 a 6) ? Consentimiento informado por escrito firmado por el representante o representantes legales de acuerdo con la normativa local y, posiblemente, formulario de asentimiento del niño o adolescente (específico de país/edad) |
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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 01. Pacientes en los que el tratamiento con anticoagulantes está contraindicado,
E 02. Tratamiento programado con otros antitrombóticos en las 2 semanas anteriores a la inclusión y durante el transcurso del estudio,
E 03. Cualquier exposición previa a AVE5026 (p. ej., inclusión previa en este estudio),
E 04. Antecedentes documentados de trombocitopenia inducida por heparina,
E 05. Trombocitopenia severa (plaquetas <50 x 109/l),
E 06. Hemorragia activa,
E 07. Cirugía cerebral, vertebral u oftalmológica reciente (menos de 3 semanas antes de la inclusión)
E 08. Hipertensión no controlada que se caracteriza por una presión arterial sistólica o diastólica mantenida superior a 2 desviaciones estándar por encima de la norma según la edad,
E 09. Enfermedad hepática severa (es decir, enzimas hepáticas más de 2,5 veces el límite superior de la normalidad correspondiente a la edad),
E 10. Insuficiencia renal severa (aclaramiento de creatinina estimado < 30 ml/min según la formula de Schwartz (véase el Anexo A),
E 11. Cualquier afección que, en opinión del investigador, pueda exponer al paciente a una relación riesgo/beneficio desfavorable,
E 12. Presencia o antecedentes de hipersensibilidad medicamentosa,
E 13. Cualquier paciente que participe actualmente en otro ensayo clínico con un fármaco en investigación según la normativa aplicable,
E 14. Cualquier paciente o padre(s)/tutor legal que, en opinión del investigador, es probable que no cumpla durante el estudio, o que sea incapaz de cooperar debido a un problema idiomático o a un retraso mental,
E 15. Cualquier paciente o padre(s)/tutor legal con el que no se pueda contactar en caso de emergencia.
E 16. Mujeres embarazadas o en período de lactancia,
E 17. Mujeres en edad fértil que no estén dispuestas a abstenerse de mantener relaciones sexuales y, por lo tanto, puedan quedar embarazadas, y no utilizan un método anticonceptivo altamente eficaz y/o que no estén dispuestas a realizarse una prueba de embarazo o sean incapaces. |
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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). |
Fármacocinética: Concetraciones plasmáticas de AVE5026. Los parámetros farmacocinéticos individuales de AVE5026 en niños se obtendrán de un modelo FC poblacional completo (incluida la evaluación de las covariables). Actividad farmacodinámica (actividad anti-Xa) de AVE5026 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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 |
Los parámetros de seguridad incluida hemorragia, necesidad de transfusiones, hemoglobina, recuento de plaquetas, datos analíticos hepáticos y renales y acontecimientos adversos (AA) graves o no graves serán monitorizados por el CMD. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
up to 30+/- 2 days post treatment |
hasta 30, +/-2 días de después de tratamiento |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | No |
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 |
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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
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LVLS |
Última visita del último paciente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |