Study of AVE5026 at Weight-adjusted Doses in Children With a Central Venous Line

Phase 2

Terminated

Conditions: Thrombosis Prophylaxis (Risk of Thrombosis Due to Central Venous Line (CVL)

Brief Summary: Primary Objective:

- To assess the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of Semuloparin \[AVE5026\] (assessed from the anti-Xa activity of Semuloparin) in children in order to determine the dose to be assessed in a clinical efficacy/safety study in this population.

Secondary Objective:

- To assess the tolerability of Semuloparin when administered at a weight-adjusted, once daily dose for up to 30 days in patients less than 18 years of age with central venous line.

Detailed Description: The maximum study duration for a participant was 68 days broken down as follows:

* Screening period: up to 6 days,

* Treatment period: minimum 6 days and maximum 30 days,

* Follow-up period with an end of study visit performed 4 weeks (30 +/-2 days) post treatment.

Enrollment staggered by age group starting with the older children (≥12 years). In each younger age group, enrolment was planned to initiate only following a review by the Data Monitoring Committee (DMC) of the clinical safety data and available PK and PD data from the first 3 out of 7 children from the previous older age group. Enrollment of infants \<3 months was planned to initiate after recruitment of all patients ≥3 months had been completed and all data analyzed by the DMC.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Age group from 6 to 12 (<) years	Semuloparin sodium	Semuloparin sodium, weight-adjusted dose once daily for 6-30 days
Age group from 2 to 6 (<) years	Semuloparin sodium	Semuloparin sodium, weight-adjusted dose once daily for 6-30 days
Age group from 3 months to 2 (<) years	Semuloparin sodium	Semuloparin sodium, weight-adjusted dose once daily for 6-30 days
Age group from birth to 3 (<) months	Semuloparin sodium	Semuloparin sodium, weight-adjusted dose once daily for 6-30 days
Age group from 12 to 18 (<) years	Semuloparin sodium	Semuloparin sodium, weight-adjusted dose once daily for 6-30 days

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: Plasma concentrations of Semuloparin	6 samples; 0.5-1h and 6h after D4 injection, 1.5-4h and 12h after D5 injection, just before and 8h after D6 injection	A validated anti-Xa chromogenic enzyme assay, with addition of AT-III in excess was to be used to assess plasma concentrations of semuloparin. A full population PK model of semuloparin in children (including covariates assessment) was to be established and individual pharmacokinetic parameters were be estimated.
Pharmacodynamic activity (anti-Xa activity) of Semuloparin	6 samples; 0.5-1h and 6h after D4 injection, 1.5-4h and 12h after D5 injection, just before and 8h after D6 injection	A validated anti-Xa chromogenic enzyme assay, without addition of AT-III in excess, was to be used to assess pharmacodynamic activity (factor Xa inhibition) of semuloparin. A full population PK/PD model of semuloparin in children (including covariates assessment) was to be established and individual pharmacodynamic parameters were to be estimated.

Secondary Outcome Measures

Name	Time	Method
Safety parameters including liver and renal laboratory data	up to 30+/- 2 days post treatment
Safety parameters including serious adverse events	up to 30+/- 2 days post treatment
Safety parameters including bleeding	up to 30+/- 2 days post treatment
Safety parameters including non-serious adverse events	up to 30+/- 2 days post treatment
Safety parameters including transfusions requirement	up to 30+/- 2 days post treatment
Safety parameters including hemoglobin, platelet count	up to 30+/- 2 days post treatment