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

NCT01567904 | Terminated Phase 2 DMC

• 3 other identifiers: PKM112042011-005155-14U1111-1115-8281
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

thrombosis; Central Venous Line; CVL

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics: Plasma concentrations of Semuloparin

  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.

  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

• Pharmacodynamic activity (anti-Xa activity) of Semuloparin

  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.

  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

Secondary Outcomes (6)

• Safety parameters including bleeding

  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

• 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

Study Arms (5)

Age group from 12 to 18 (<) years

EXPERIMENTAL

Semuloparin sodium, weight-adjusted dose once daily for 6-30 days

Drug: Semuloparin sodium

Age group from 6 to 12 (<) years

EXPERIMENTAL

Semuloparin sodium, weight-adjusted dose once daily for 6-30 days

Drug: Semuloparin sodium

Age group from 2 to 6 (<) years

EXPERIMENTAL

Semuloparin sodium, weight-adjusted dose once daily for 6-30 days

Drug: Semuloparin sodium

Age group from 3 months to 2 (<) years

EXPERIMENTAL

Semuloparin sodium, weight-adjusted dose once daily for 6-30 days

Drug: Semuloparin sodium

Age group from birth to 3 (<) months

EXPERIMENTAL

Semuloparin sodium, weight-adjusted dose once daily for 6-30 days

Drug: Semuloparin sodium

Interventions

Semuloparin sodium DRUG

Solution for injection in single dose vials (10 mg/mL and 20 mg/mL) Subcutaneous injection

Also known as: AVE5026

Age group from 12 to 18 (<) years; Age group from 2 to 6 (<) years; Age group from 3 months to 2 (<) years; Age group from 6 to 12 (<) years; Age group from birth to 3 (<) months

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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;

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Investigational Site Number 348001

Budapest, 1094, Hungary

Location

MeSH Terms

Conditions

Thrombosis

Interventions

AVE 5026

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: March 30, 2012
• Study Start: May 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: May 3, 2016

Record last verified: 2016-04

Locations

HU (1)