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

This study has been terminated.
(due to the decision from sanofi to withdraw on a worldwide basis the Marketing Authorisation Applications for semuloparin in the adult indication)
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01567904
First received: March 28, 2012
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

Primary Objective:

- To assess the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of Semuloparin (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.


Condition Intervention Phase
Thrombosis Prophylaxis (Risk of Thrombosis Due to Central Venous Line (CVL)
Drug: Semuloparin sodium
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: An Open-label, Pharmacokinetic, Pharmacodynamic, and Tolerability Study of AVE5026 Administered at Weight-adjusted Doses to Patients Less Than 18 Years of Age With a Central Venous Line (CVL)

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Pharmacokinetics: Plasma concentrations of Semuloparin [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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 [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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:
  • Safety parameters including bleeding [ Time Frame: up to 30+/- 2 days post treatment ] [ Designated as safety issue: Yes ]
  • Safety parameters including transfusions requirement [ Time Frame: up to 30+/- 2 days post treatment ] [ Designated as safety issue: Yes ]
  • Safety parameters including hemoglobin, platelet count [ Time Frame: up to 30+/- 2 days post treatment ] [ Designated as safety issue: Yes ]
  • Safety parameters including liver and renal laboratory data [ Time Frame: up to 30+/- 2 days post treatment ] [ Designated as safety issue: Yes ]
  • Safety parameters including serious adverse events [ Time Frame: up to 30+/- 2 days post treatment ] [ Designated as safety issue: Yes ]
  • Safety parameters including non-serious adverse events [ Time Frame: up to 30+/- 2 days post treatment ] [ Designated as safety issue: Yes ]

Enrollment: 2
Study Start Date: May 2012
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Age group from 12 to 18 (<) years
Semuloparin sodium, weight-adjusted dose once daily for 6-30 days
Drug: Semuloparin sodium

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

Subcutaneous injection

Other Name: AVE5026
Experimental: Age group from 6 to 12 (<) years
Semuloparin sodium, weight-adjusted dose once daily for 6-30 days
Drug: Semuloparin sodium

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

Subcutaneous injection

Other Name: AVE5026
Experimental: Age group from 2 to 6 (<) years
Semuloparin sodium, weight-adjusted dose once daily for 6-30 days
Drug: Semuloparin sodium

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

Subcutaneous injection

Other Name: AVE5026
Experimental: Age group from 3 months to 2 (<) years
Semuloparin sodium, weight-adjusted dose once daily for 6-30 days
Drug: Semuloparin sodium

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

Subcutaneous injection

Other Name: AVE5026
Experimental: Age group from birth to 3 (<) months
Semuloparin sodium, weight-adjusted dose once daily for 6-30 days
Drug: Semuloparin sodium

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

Subcutaneous injection

Other Name: AVE5026

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.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01567904

Locations
Hungary
Investigational Site Number 348001
Budapest, Hungary, 1094
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01567904     History of Changes
Other Study ID Numbers: PKM11204, 2011-005155-14, U1111-1115-8281
Study First Received: March 28, 2012
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
thrombosis
Central Venous Line
CVL

Additional relevant MeSH terms:
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 22, 2014