Decision from Sanofi to withdraw on a worldwide basis the Marketing Authorisation Applications for Semuloparin sodium in the adult indication

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.

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.

Inclusion criteria :

• 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).

Exclusion criteria:

• Patient for whom anticoagulant therapy was contraindicated;
• Planned treatment with other antithrombotic agents within 2 weeks prior to enrolment and during the course of the study;
• Any previous exposure to Semuloparin (e.g. previous enrolment in the current study);
• Documented history of heparin-induced thrombocytopenia;
• Severe thrombocytopenia (platelets <50 x 109/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 have exposed 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, was 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 could not be contacted in case of emergency;
• Pregnant or breast-feeding female;
• Female of childbearing potential who were unwilling to abstain from sexual intercourse and therefore were at risk of becoming pregnant and were not protected by highly effective contraceptive method of birth control and/or who were unwilling or unable to be tested for pregnancy.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.