Clinical Trial Results:
A 12-week, Multicenter, Pharmacokinetic and Safety Study of Human Plasma-Derived Factor XIII Concentrate in Subjects with Congential Factor XIII Deficiency
Estudio de 12 semanas, multicéntrico, de farmacocinética y seguridad del concentrado de factor XIII derivado del plasma humano en sujetos con deficiencia congénita de factor XIII
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Summary
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EudraCT number |
2009-010387-41 |
Trial protocol |
ES |
Global end of trial date |
24 Feb 2010
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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 |
BI71023_2002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00883090 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CSL Behring LLC
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Sponsor organisation address |
1020 First Avenue, King of Prussia, United States, 19406-0901
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Public contact |
Clinical Trial Disclosure Manager, CSL Behring, clinicaltrials@cslbehring.com
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Scientific contact |
Clinical Trial Disclosure Manager, CSL Behring, 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 |
04 May 2010
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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 |
24 Feb 2010
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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 |
The primary objective of this study is to generate steady-state PK Factor XIII data in subjects with congential Factor XIII 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 |
18 May 2009
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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 |
Spain: 5
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Country: Number of subjects enrolled |
United States: 10
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Worldwide total number of subjects |
15
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EEA total number of subjects |
5
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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) |
3
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Adolescents (12-17 years) |
2
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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 |
Eligible subjects had documented congenital FXIII deficiency requiring prophylactic treatment with a FXIII containing product. Males and females of any age with congenital FXIII deficiency could participate in the study. | ||||||||||||||
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Pre-assignment
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Screening details |
At the Screening Visit, blood for determination of viral markers, serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, and, if female of childbearing potential, pregnancy testing was obtained. | ||||||||||||||
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Period 1
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Period 1 title |
Overall trial (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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Factor XIII | ||||||||||||||
Arm description |
Subjects received 40 U/kg of Factor XIII per administration every 28 days for 3 doses administered as a bolus IV injection. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Factor XIII Concentrate (Human)
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Investigational medicinal product code |
B17023
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Other name |
Fibrogammin® P, Cluvot®
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received 40 U/kg of Factor XIII Concentrate (Human) per administration every 28 days for 3 doses administered as a bolus intravenous (IV) injection at 250 U/minute (when reconstituted 250 U/minute equals 4mL/minute).
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Baseline characteristics reporting groups
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Reporting group title |
Factor XIII
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Reporting group description |
Subjects received 40 U/kg of Factor XIII per administration every 28 days for 3 doses administered as a bolus IV injection. | ||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Factor XIII
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Reporting group description |
Subjects received 40 U/kg of Factor XIII per administration every 28 days for 3 doses administered as a bolus IV injection. | ||
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End point title |
Peak FXIII Concentration at Steady State [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 weeks
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| 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: No formal testing of hypotheses was performed. |
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| Notes [2] - The PK population comprised all subjects in the safety population who completed the study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Trough FXIII Concentration at Steady State [3] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 weeks
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| 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: No formal testing of hypotheses was performed. |
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| Notes [4] - PK population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Peak Concentration [5] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [5] - 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: No formal testing of hypotheses was performed. |
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| Notes [6] - PK population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Incremental Recovery [7] | ||||||||
End point description |
Incremental recovery is defined as the maximum (peak) FXIII activity (IU/mL) obtained after infusion, per dose of FXIII (IU/kg) administered.
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [7] - 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: No formal testing of hypotheses was performed. |
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| Notes [8] - PK population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Terminal Half-life [9] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [9] - 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: No formal testing of hypotheses was performed. |
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| Notes [10] - PK population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Curve at Steady State [11] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [11] - 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: No formal testing of hypotheses was performed. |
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| Notes [12] - PK Population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Clearance [13] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [13] - 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: No formal testing of hypotheses was performed. |
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| Notes [14] - PK population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Volume of Distribution at Steady State [15] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [15] - 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: No formal testing of hypotheses was performed. |
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| Notes [16] - PK population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Residence Time [17] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [17] - 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: No formal testing of hypotheses was performed. |
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| Notes [18] - PK population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants with Adverse Events | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
16 weeks
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| Notes [19] - The safety population comprised all subjects who received a dose of Factor XIII. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants with Clinically Significant Laboratory Safety Parameter Values | ||||||
End point description |
Number of participants with clinically significant laboratory safety parameter values. The laboratory safety parameters measured included serum chemistries, hematology and urinalysis.
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End point type |
Secondary
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End point timeframe |
16 weeks
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| Notes [20] - Safety population |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants with Clinically Significant Vital Signs | ||||||
End point description |
Number of participants with clinically significant vital signs. The vital signs measured included blood pressure, pulse rate and temperature. Clinically significant changes in vital signs were to be reported as adverse events.
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End point type |
Secondary
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End point timeframe |
16 weeks
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| Notes [21] - safety population |
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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 |
The time frame for adverse event (AE) reporting was up to 16 weeks and comprised the time from giving written informed consent (during screening) to 28 days after the last administration of study treatment.
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Adverse event reporting additional description |
Reporting group is comprised of all subjects treated with Factor FXIII Concentrate (Human) (FXIII).
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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 |
12.0
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Reporting groups
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Reporting group title |
Factor XIII
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Reporting group description |
Subjects received 40 U/kg of Factor XIII per administration every 28 days for 3 doses administered as a bolus IV injection. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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04 Feb 2009 |
The dose for all 3 treatments was calculated based on screening weight rather than baseline weight
Updated the inclusion criteria to include males and females of any age with congenital Factor XIII deficiency
The AE reporting requirement was changed from 30 days to 28 days
Removed the requirement to collect further information if any AEs were experienced after discontinuing participation in the study |
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09 Jul 2009 |
The number of subjects planned for enrollment was updated to “approximately” 15
An inclusion criterion was changed from “Eligible subjects will have been diagnosed with severe congenital Factor XIII deficiency (<10 U/dL at diagnosis)” to “Eligible subjects will have documented congenital Factor XIII deficiency that requires prophylactic treatment with a Factor XIII containing product”
Updated the inclusion criteria to include receipt of full hepatitis B vaccination and/or was hepatitis B surface antibody positive
Excluded subjects with known or suspected to have antibodies towards Factor XIII
Removed the following exclusion criterion: “Negative serology for hepatitis B and has not received a full hepatitis B vaccination”
Updated the PK statistical analysis to include calculation with and without adjustment for any unknown remaining endogenous Factor XIII levels
Added guidance for subjects who experienced a bleeding event requiring additional dosing with a Factor XIII-containing product
Added guidance for subjects who were actively bleeding at the time of Dose 3 (main PK visit)
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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 | |||
