Clinical Trial Results:
An open-label, pharmacokinetic, pharmacodynamic, and tolerability study of AVE5026 administered at weight-adjusted doses to patients under 18 years of age with a Central Venous Line (CVL)
|
Summary
|
|
EudraCT number |
2011-005155-14 |
Trial protocol |
HU ES SK Outside EU/EEA |
Global end of trial date |
10 Jul 2012
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
23 May 2016
|
First version publication date |
05 Nov 2014
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
PKM11204
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01567904 | ||
WHO universal trial number (UTN) |
U1111-1115-8281 | ||
|
Sponsors
|
|||
Sponsor organisation name |
Sanofi Aventis Recherche & Developpement
|
||
Sponsor organisation address |
1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
|
||
Public contact |
Trial Transparency Team, Sanofi Aventis Recherche & Developpement, Contact-US@sanofi.com
|
||
Scientific contact |
Trial Transparency Team, Sanofi Aventis Recherche & Developpement, Contact-US@sanofi.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-000562-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
18 Jul 2012
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
10 Jul 2012
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To determine the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of Semuloparin (AVE5026) (assessed from the anti-Xa activity of of the compound) in children in order to determine the dose to be assessed in the subsequent clinical efficacy/safety study
|
||
Protection of trial subjects |
The study was conducted by investigators experienced in the treatment of pediatric patients. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesic may have been used to minimize distress and discomfort.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 May 2012
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Hungary: 2
|
||
Worldwide total number of subjects |
2
|
||
EEA total number of subjects |
2
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
2
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||
|
Recruitment
|
|||||||||
Recruitment details |
The study was early terminated per Sponsor decision after two subjects were enrolled in the first age group. The decision has been taken in keeping with the Company’s decision to withdraw, on a worldwide basis, the marketing authorization applications [MAA] for semuloparin in adult indication. | ||||||||
|
Pre-assignment
|
|||||||||
Screening details |
Enrollment was to stagger by age group starting with the older children (≥12 years). Enrollment in a younger age group was planned to initiate only following a review by the Data Monitoring Committee 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. | ||||||||
|
Period 1
|
|||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||
Is this the baseline period? |
Yes | ||||||||
Allocation method |
Not applicable
|
||||||||
Blinding used |
Not blinded | ||||||||
|
Arms
|
|||||||||
|
Arm title
|
Semuloparin - 12 to <18 years (group 1) | ||||||||
Arm description |
Semuloparin sodium for 6-30 days to children aged from 12 to <18 years | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
Semuloparin sodium
|
||||||||
Investigational medicinal product code |
AVE5026
|
||||||||
Other name |
|||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||
Routes of administration |
Subcutaneous use
|
||||||||
Dosage and administration details |
Weight-adjusted dose, 0.3 milligram per kilogram (mg/kg), once daily
|
||||||||
|
|||||||||
|
||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||
Reporting group title |
Semuloparin - 12 to <18 years (group 1)
|
|||||||||||||||||||||||||||||||||
Reporting group description |
Semuloparin sodium for 6-30 days to children aged from 12 to <18 years | |||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Semuloparin - 12 to <18 years (group 1)
|
||
Reporting group description |
Semuloparin sodium for 6-30 days to children aged from 12 to <18 years | ||
|
|||||||||
End point title |
Pharmacokinetic (PK): Plasma concentration [1] | ||||||||
End point description |
A validated anti-Xa chromogenic enzyme assay, with addition of Antithrombin(AT)-III in excess, was to be used to assess plasma concentrations of Semuloparin.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Up to a maximum of 6 samples between Day 4, Day 5 and Day 6.
The number of samples and the timing was adjusted according to the age of the child.
|
||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to early termination of the study, no PK parameters were determined. |
|||||||||
|
|||||||||
| Notes [2] - Due to early termination of the study, no PK parameters were determined. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Pharmacodynamic (PD): Factor Xa inhibition [3] | ||||||||
End point description |
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.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Up to a maximum of 6 samples between Day 4, Day 5 and Day 6.
The number of samples and the timing was adjusted according to the age of the child.
|
||||||||
| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to early termination of the study, no PD parameters were determined. |
|||||||||
|
|||||||||
| Notes [4] - Due to early termination of the study, no PD parameters were determined. |
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||
End point title |
Safety: Number of subjects with bleeding events | ||||||
End point description |
|||||||
End point type |
Secondary
|
||||||
End point timeframe |
up to 30 +/- 2 days post treatment
|
||||||
|
|||||||
| Notes [5] - Safety population: All subjects enrolled and exposed to the compound. |
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||
End point title |
Safety: Number of subjects requiring blood transfusion | ||||||
End point description |
|||||||
End point type |
Secondary
|
||||||
End point timeframe |
up to 30 +/- 2 days post treatment
|
||||||
|
|||||||
| Notes [6] - Safety population: All subjects enrolled and exposed to the compound |
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (30 +/- 2 days after end of treatment) regardless of seriousness or relationship to investigational product.
|
||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Reported AEs are treatment-emergent adverse events i.e. AEs that developed/worsened during the ‘on treatment period’ (from the first dose up to 3 days after the last dose of study drug).
|
||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Semuloparin - 12 to <18 years (group 1)
|
||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Semuloparin sodium for 6-30 days to children aged from 12 to <18 years | ||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
