Clinical Trial Results:
Pharmacokinetics of Haemocomplettan P in subjects with congenital fibrinogen deficiency
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Summary
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EudraCT number |
2006-006023-39 |
Trial protocol |
IT |
Global end of trial date |
13 May 2008
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Jul 2016
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First version publication date |
06 Aug 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BI3023_2001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00496262 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CSL Behring GmbH
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Sponsor organisation address |
Emil-von-Behring-Strasse 76, Marburg, Germany, 35041
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Public contact |
Trial Disclosure Manager, CSL Behring GmbH, clinicaltrials@cslbehring.com
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Scientific contact |
Trial Disclosure Manager, CSL Behring GmbH, clinicaltrials@cslbehring.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 May 2008
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 May 2008
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare maximum clot strength (maximum clot firmness [MCF]) as a surrogate marker for hemostatic efficacy before and after administration of Haemocomplettan P in subjects with congenital fibrinogen deficiency and to demonstrate that MCF 1 hour after administration of 70 mg/kg b.w. of Haemocomplettan P is significantly higher compared to baseline.
To determine the single dose pharmacokinetics (PK) of Haemocomplettan P in subjects with congenital fibrinogen deficiency.
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Protection of trial subjects |
This study was carried out in accordance with the International Conference on Harmonisation (ICH)
Good Clinical Practice guidelines, and standard operating procedures for clinical research and
development at CSL Behring (CSLB).
The study protocol and all amendments were approved by the Independent Ethics Committee(s) (IECs) /
Institutional Review Board(s) (IRBs) of the participating centers.
Before undergoing screening procedures for possible enrollment into the study, subjects were informed,
in an understandable form, about the nature, scope, and possible consequences of the study. The
investigator was responsible for obtaining a subject’s written informed consent to participate in the
study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Jul 2007
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 8
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Country: Number of subjects enrolled |
United States: 7
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Worldwide total number of subjects |
15
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EEA total number of subjects |
8
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
2
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Adolescents (12-17 years) |
3
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Adults (18-64 years) |
10
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
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Pre-assignment
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Screening details |
Overall, 17 subjects were screened for this study and 15 subjects were enrolled. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Human Fibrinogen Concentrate | ||||||
Arm description |
All enrolled subjects received a single intravenous infusion of 70 mg/kg body weight of human fibrinogen concentrate. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Human fibrinogen concentrate, pasteurized
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Investigational medicinal product code |
BI3023
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Other name |
Haemocomplettan® P
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Pharmaceutical forms |
Powder and solvent for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
A single dose of 70 mg fibrinogen per kg body weight. Supplied as 1 g lyophilizate to be reconstituted in 50 mL of sterile water for injection. Final concentration for infusion was 20 mg/mL.
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Baseline characteristics reporting groups
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Reporting group title |
Human Fibrinogen Concentrate
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Reporting group description |
All enrolled subjects received a single intravenous infusion of 70 mg/kg body weight of human fibrinogen concentrate. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Human Fibrinogen Concentrate
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Reporting group description |
All enrolled subjects received a single intravenous infusion of 70 mg/kg body weight of human fibrinogen concentrate. | ||
Subject analysis set title |
Pharmacokinetic Analysis Population
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The pharmacokinetics analysis population included all subjects in the ITT population who fulfilled all of the following conditions:
· Received 90% of the planned total dose of Haemocomplettan P.
· Did not meet any of the exclusion criteria.
· Did not receive any fibrinogen containing blood products between infusion of Haemocomplettan P and the end of the 14-day PK observation period.
· Provided sufficient PK data that allowed for a reliable PK analysis.
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Subject analysis set title |
Pre-infusion
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Less than or equal to 2 hours before start of infusion
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Subject analysis set title |
1 Hour Post-infusion
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
1 hour after end of infusion
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End point title |
Change From Pre-infusion to One-hour Post-infusion in Maximum Clot Firmness (MCF) | |||||||||||||||
End point description |
MCF is a functional parameter that depends on the activation of coagulation, the fibrinogen content of the sample (in plasma), and the polymerization and crosslinking of the fibrin network. MCF was determined by rotational thromboelastometry (ROTEM) testing.
The entire ITT population was used for a conservative analysis of the mean change in MCF. The mean change was set to 0 for any subject with missing MCF data.
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End point type |
Primary
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End point timeframe |
Pre-infusion and one hour post-infusion
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Statistical analysis title |
Statistical Analysis 1 for Maximum Clot Firmness | |||||||||||||||
Statistical analysis description |
The entire ITT population was used for a conservative analysis of the mean change in MCF. The mean change was set to 0 for any subject with missing MCF data.
Although the number of subjects included in analysis lists 30, the correct number is 15. Due to system constraints, this field is not able to be edited.
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Comparison groups |
Pre-infusion v 1 Hour Post-infusion
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
< 0.0001 | |||||||||||||||
Method |
t-test, 2-sided | |||||||||||||||
Confidence interval |
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End point title |
Terminal Elimination Half-life (t1/2) for Fibrinogen Activity | ||||||||
End point description |
Fibrinogen activity was measured using the Clauss assay. The detection limit for fibrinogen activity is 0.2 g/L.
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End point type |
Secondary
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End point timeframe |
0.5 hours to 13 days post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Concentration (Cmax) for Fibrinogen Activity | ||||||||
End point description |
Fibrinogen activity was measured using the Clauss assay. The detection limit for fibrinogen activity is 0.2 g/L.
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End point type |
Secondary
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End point timeframe |
Pre-infusion to 13 days post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Concentration-time Curve (AUC) Standardized for 70 mg/kg Body Weight Dose | ||||||||
End point description |
Fibrinogen activity was measured using the Clauss assay. The detection limit for fibrinogen activity is 0.2 g/L.
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End point type |
Secondary
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End point timeframe |
Pre-infusion to 13 days post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Clearance (Cl) for Fibrinogen Activity | ||||||||
End point description |
Fibrinogen activity was measured using the Clauss assay. The detection limit for fibrinogen activity is 0.2 g/L.
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End point type |
Secondary
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End point timeframe |
Pre-infusion to 13 days post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Residence Time (MRT) for Fibrinogen Activity | ||||||||
End point description |
Fibrinogen activity was measured using the Clauss assay. The detection limit for fibrinogen activity is 0.2 g/L.
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End point type |
Secondary
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End point timeframe |
Pre-infusion to 13 days post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Volume of Distribution at Steady State (Vss) for Fibrinogen Activity | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Pre-infusion to 13 days post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Incremental In Vivo Recovery for Fibrinogen Activity | ||||||||
End point description |
The maximum fibrinogen increase in plasma, per mg/kg body weight (b.w.). dosed, within 4 hours of infusion compared to pre-infusion.
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End point type |
Secondary
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End point timeframe |
Pre-infusion to 4 hours post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Classical In Vivo Recovery for Fibrinogen Activity | ||||||||
End point description |
The maximum fibrinogen increase in plasma, per mg/mL plasma volume dosed, within 4 hours of infusion.
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End point type |
Secondary
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End point timeframe |
Pre-infusion to 4 hours post-infusion
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the first dose of study drug up until 44 days after administration of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.0
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Reporting groups
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Reporting group title |
Human Fibrinogen Concentrate
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Reporting group description |
All enrolled subjects received a single intravenous infusion of 70 mg/kg body weight of human fibrinogen concentrate. | ||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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08 Oct 2007 |
Substantial Amendment No. 1 covered the following changes:
1. The time for the analysis of the screening sample was shortened from that given before (at least 4 weeks) to allow the subject to be treated as soon as the confirmed screening results were available.
2. A time specification (1 year prior to enrollment) was added for the exclusion criteria “presence or history of deep vein thrombosis or pulmonary embolism or of arterial thrombosis”. This was justified as both conditions can be part of the underlying disease, and it is not medically indicated to exclude patients who have experienced these conditions more than 1 year prior to enrollment. Patients who have thromboembolic events in their medical history will also be in the population that is targeted to be treated with the product, because it is part of the underlying disease.
3. The last virus safety follow-up was changed to Day 45 instead of Month 3 because tests available (PCR) can already assess a potential virus transmission after 45 days. The shorter study period is more convenient for patients and investigators and the validity of the 45 days virus safety follow-up is scientifically equivalent to a 3-month virus safety follow-up.
4. Department name and staff changes were indicated. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
