Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An Open-Label, Multi-Centre Extension Study to Assess the Efficacy and Safety of Biostate® in Paediatric, Adolescent, and Adult Subjects with Von Willebrand Disease who Completed Clinical Studies CSLCT-BIO-08-52 or CSLCTBIO-08-54

    Summary
    EudraCT number
    		 2009-017301-11
    Trial protocol
    		 BG   PL   DE  
    Global end of trial date
    28 Mar 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Jul 2016
    First version publication date
    06 Aug 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CSLCT-BIO-09-64
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    CSL Behring GmbH
    Sponsor organisation address
    Emil-von-Behring-Str. 76, Marburg, Germany, 35041
    Public contact
    Clinical Trial Disclosure Manager, CSL Behring, clinicaltrials@cslbehring.com
    Scientific contact
    Clinical Trial Disclosure Manager, CSL Behring, clinicaltrials@cslbehring.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 May 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Mar 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives were: • To assess the effectiveness of a prophylaxis regimen as compared to on-demand therapy with Biostate in preventing non-surgical bleeding (NSB) events. • To assess the haemostatic efficacy of Biostate in subjects with Von Willebrand disease (VWD) who require a Von Willebrand factor (VWF) product to control an NSB event.
    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. The investigator may cease study treatment and withdraw the subject, or the subject may withdraw himself from participation in the study at any time. If a subject is withdrawn from the study or further participation is declined, the subject will continue to have access to medical care and will be treated according to routine medical practice, but will no longer receive the investigational medicinal product (IMP).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Oct 2010
    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
    Bulgaria: 6
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Poland: 4
    Country: Number of subjects enrolled
    Russian Federation: 4
    Country: Number of subjects enrolled
    Ukraine: 3
    Worldwide total number of subjects
    20
    EEA total number of subjects
    13
    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)
    3
    Adolescents (12-17 years)
    2
    Adults (18-64 years)
    14
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Three subjects were enrolled in this extension study from study 2009-017753-34 (CSLCT-BIO-08-52) and 17 subjects from study 2008-004922-18 (CSLCT-BIO-08-54).

    Pre-assignment
    Screening details
    		 After eligibility of the subject was confirmed by prior participation and completion of study 2009-017753-34 (CSLCT-BIO-08-52) and 17 subjects from study 2008-004922-18 (CSLCT-BIO-08-54), the subject was admitted to this study. Visit 1 (Day 1) of this study should have coincided with the Final Visit of the subject's respective previous study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Prophylaxis Arm
    Arm description
    		 Single bolus doses were administered intravenously as required to manage the subject's VWD. Subjects received Biostate on a regular basis 1-3 times per week as part of a prophylactic therapy regimen. Individual doses and regimen were determined by the investigator based on the subject’s clinical condition, previous Factor VIII (FVIII) / VWF concentrate requirements, response to therapy, body weight, and reason for usage.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Human coagulation Factor VIII / von Willebrand Factor
    Investigational medicinal product code
    Other name
    Biostate®, Voncento®
    Pharmaceutical forms
    Powder and solvent for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Biostate was administrated intravenously as a bolus dose at a maximum infusion rate of 6 mL/min as tolerated by the subject.

    Arm title
    		 On-demand Arm
    Arm description
    		 Single bolus doses were administered intravenously as required to manage the stubject's VWD. Subjects received Biostate to treat a spontaneous or traumatic bleeding event, to provide haemostatic control during a surgical procedure. If subjects used Biostate for irregular prevention of bleedings this was recorded as “on-demand” treatment. Individual doses and regimen were determined by the investigator based on the subject’s clinical condition, previous FVIII / VWF concentrate requirements, response to therapy, body weight, and reason for usage.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Human coagulation Factor VIII / von Willebrand Factor
    Investigational medicinal product code
    Other name
    Biostate®, Voncento®
    Pharmaceutical forms
    Powder and solvent for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Biostate was administrated intravenously as a bolus dose at a maximum infusion rate of 6 mL/min as tolerated by the subject.

    Arm title
    		 Prophylaxis and On-demand Arm
    Arm description
    		 Single bolus doses were administered intravenously as required to manage their VWD. Subjects received Biostate to treat a spontaneous or traumatic bleeding event, to provide haemostatic control during a surgical procedure, or on a regular basis 1-3 times per week as part of a prophylactic therapy regimen. If subjects used Biostate for irregular prevention of bleedings this was recorded as “on-demand” treatment. Individual doses were determined by the investigator based on the subject’s clinical condition, previous FVIII / VWF concentrate requirements, response to therapy, body weight, and reason for usage.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Human coagulation Factor VIII / von Willebrand Factor
    Investigational medicinal product code
    Other name
    Biostate®, Voncento®
    Pharmaceutical forms
    Powder and solvent for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Biostate was administrated intravenously as a bolus dose at a maximum infusion rate of 6 mL/min as tolerated by the subject.

    Number of subjects in period 1
    		Prophylaxis Arm On-demand Arm Prophylaxis and On-demand Arm
    Started
    10
    8
    2
    Received at least 1 dose of Biostate
    10
    7
    2
    Completed
    9
    7
    2
    Not completed
    1
    1
    0
         Investigator's decision
    1
    -
    -
         Death
    -
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Prophylaxis Arm
    Reporting group description
    		 Single bolus doses were administered intravenously as required to manage the subject's VWD. Subjects received Biostate on a regular basis 1-3 times per week as part of a prophylactic therapy regimen. Individual doses and regimen were determined by the investigator based on the subject’s clinical condition, previous Factor VIII (FVIII) / VWF concentrate requirements, response to therapy, body weight, and reason for usage.

    Reporting group title
    On-demand Arm
    Reporting group description
    		 Single bolus doses were administered intravenously as required to manage the stubject's VWD. Subjects received Biostate to treat a spontaneous or traumatic bleeding event, to provide haemostatic control during a surgical procedure. If subjects used Biostate for irregular prevention of bleedings this was recorded as “on-demand” treatment. Individual doses and regimen were determined by the investigator based on the subject’s clinical condition, previous FVIII / VWF concentrate requirements, response to therapy, body weight, and reason for usage.

    Reporting group title
    Prophylaxis and On-demand Arm
    Reporting group description
    		 Single bolus doses were administered intravenously as required to manage their VWD. Subjects received Biostate to treat a spontaneous or traumatic bleeding event, to provide haemostatic control during a surgical procedure, or on a regular basis 1-3 times per week as part of a prophylactic therapy regimen. If subjects used Biostate for irregular prevention of bleedings this was recorded as “on-demand” treatment. Individual doses were determined by the investigator based on the subject’s clinical condition, previous FVIII / VWF concentrate requirements, response to therapy, body weight, and reason for usage.

    Reporting group values
    		 Prophylaxis Arm On-demand Arm Prophylaxis and On-demand Arm Total
    Number of subjects
    		 10 8 2 20
    Age categorical
    Units: Subjects
        6 to < 12 years
    		 3 0 0 3
        12 to < 18 years
    		 0 1 1 2
        >= 18 years
    		 7 7 1 15
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 35.8 ( 23.02 ) 28.4 ( 11.94 ) 28 ( 16.97 ) -
    Gender categorical
    Units: Subjects
        Female
    		 2 6 0 8
        Male
    		 8 2 2 12
    Subject analysis sets

    Subject analysis set title
    Prophylaxis - Safety/Efficacy/Per-protocol Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Prophylaxis Arm were included in the Safety/Efficacy/Per-protocol sets.

    Subject analysis set title
    On-demand - Safety/Efficacy/Per-protocol Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    One subject in the on-demand arm did not receive any Biostate during this extension study and was therefore excluded from the analysis populations used for efficacy and safety analyses.

    Subject analysis set title
    Prophylaxis and On-demand - Safety/Efficacy/Per-protocol Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Prophylaxis and On-demand Arm were included in the Safety/Efficacy/Per-protocol sets.

    Subject analysis sets values
    		 Prophylaxis - Safety/Efficacy/Per-protocol Set On-demand - Safety/Efficacy/Per-protocol Set Prophylaxis and On-demand - Safety/Efficacy/Per-protocol Set
    Number of subjects
    10
    7
    2
    Age categorical
    Units: Subjects
        6 to < 12 years
    3
    0
    0
        12 to < 18 years
    0
    1
    1
        >= 18 years
    7
    6
    1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    35.8 ( 23.02 )
    29.7 ( 12.23 )
    28 ( 16.97 )
    Gender categorical
    Units: Subjects
        Female
    2
    5
    0
        Male
    8
    2
    2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Prophylaxis Arm
    Reporting group description
    		 Single bolus doses were administered intravenously as required to manage the subject's VWD. Subjects received Biostate on a regular basis 1-3 times per week as part of a prophylactic therapy regimen. Individual doses and regimen were determined by the investigator based on the subject’s clinical condition, previous Factor VIII (FVIII) / VWF concentrate requirements, response to therapy, body weight, and reason for usage.

    Reporting group title
    On-demand Arm
    Reporting group description
    		 Single bolus doses were administered intravenously as required to manage the stubject's VWD. Subjects received Biostate to treat a spontaneous or traumatic bleeding event, to provide haemostatic control during a surgical procedure. If subjects used Biostate for irregular prevention of bleedings this was recorded as “on-demand” treatment. Individual doses and regimen were determined by the investigator based on the subject’s clinical condition, previous FVIII / VWF concentrate requirements, response to therapy, body weight, and reason for usage.

    Reporting group title
    Prophylaxis and On-demand Arm
    Reporting group description
    		 Single bolus doses were administered intravenously as required to manage their VWD. Subjects received Biostate to treat a spontaneous or traumatic bleeding event, to provide haemostatic control during a surgical procedure, or on a regular basis 1-3 times per week as part of a prophylactic therapy regimen. If subjects used Biostate for irregular prevention of bleedings this was recorded as “on-demand” treatment. Individual doses were determined by the investigator based on the subject’s clinical condition, previous FVIII / VWF concentrate requirements, response to therapy, body weight, and reason for usage.

    Subject analysis set title
    Prophylaxis - Safety/Efficacy/Per-protocol Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Prophylaxis Arm were included in the Safety/Efficacy/Per-protocol sets.

    Subject analysis set title
    On-demand - Safety/Efficacy/Per-protocol Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    One subject in the on-demand arm did not receive any Biostate during this extension study and was therefore excluded from the analysis populations used for efficacy and safety analyses.

    Subject analysis set title
    Prophylaxis and On-demand - Safety/Efficacy/Per-protocol Set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Prophylaxis and On-demand Arm were included in the Safety/Efficacy/Per-protocol sets.

    Primary: Investigator’s 3-monthly Assessment of Haemostatic Efficacy

    		 Close Top of page
    End point title
    		 Investigator’s 3-monthly Assessment of Haemostatic Efficacy [1]
    End point description
    The Investigator’s subjective 3-monthly assessment of haemostatic efficacy of Biostate in its usage with a NSB event, surgical procedure, or use in a prophylactic regimen. The efficacy grading scale was as follows: excellent=haemostasis achieved/cessation of bleeding; good=slight oozing/partial but adequate control of bleeding, does not require additional product for unplanned treatment; moderate=moderate bleeding/moderate control of bleeding, required additional product for unplanned treatment; none=severe uncontrolled bleeding. Subjects who did not have any bleeding events are included in this table. Not Applicable: Subject did not experience any bleeding event which required Biostate in the respective 3-monthly period.
    End point type
    Primary
    End point timeframe
    Months 3, 6, 9 12, 15, 18, 21, 24, 27, 30, 32, and Final Visit (Final Visit assessment was included in the corresponding 3-monthly period based on the Final Visit date.)
    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: Descriptive data was collected per protocol and is reported.
    End point values
    		 Prophylaxis - Safety/Efficacy/Per-protocol Set On-demand - Safety/Efficacy/Per-protocol Set Prophylaxis and On-demand - Safety/Efficacy/Per-protocol Set
    Number of subjects analysed
    10 [2]
    7 [3]
    2 [4]
    Units: subjects
        Month 3: Excellent; n=10, 7, 2
    5
    1
    0
        Month 3: Good; n=10, 7, 2
    1
    1
    0
        Month 3: Moderate; n=10, 7, 2
    0
    0
    0
        Month 3: None; n=10, 7, 2
    0
    0
    0
        Month 3: Not Applicable; n=10, 7, 2
    4
    5
    2
        Month 6: Excellent; n=10, 7, 2
    3
    3
    1
        Month 6: Good; n=10, 7, 2
    2
    1
    1
        Month 6: Moderate; n=10, 7, 2
    0
    0
    0
        Month 6: None; n=10, 7, 2
    0
    0
    0
        Month 6: Not Applicable; n=10, 7, 2
    5
    3
    0
        Month 9: Excellent; n=10, 7, 2
    4
    4
    1
        Month 9: Good; n=10, 7, 2
    2
    1
    1
        Month 9: Moderate; n=10, 7, 2
    0
    0
    0
        Month 9: None; n=10, 7, 2
    0
    0
    0
        Month 9: Not Applicable; n=10, 7, 2
    4
    2
    0
        Month 12: Excellent; n=9, 7, 2
    1
    2
    0
        Month 12: Good; n=9, 7, 2
    2
    1
    2
        Month 12: Moderate; n=9, 7, 2
    0
    0
    0
        Month 12: None; n=9, 7, 2
    0
    0
    0
        Month 12: Not Applicable; n=9, 7, 2
    6
    4
    0
        Month 15: Excellent; n=9, 5, 2
    2
    1
    1
        Month 15: Good; n=9, 5, 2
    3
    2
    1
        Month 15: Moderate; n=9, 5, 2
    0
    0
    0
        Month 15: None; n=9, 5, 2
    0
    0
    0
        Month 15: Not Applicable; n=9, 5, 2
    4
    2
    0
        Month 18: Excellent; n=9, 5, 2
    3
    0
    1
        Month 18: Good; n=9, 5, 2
    2
    4
    1
        Month 18: Moderate; n=9, 5, 2
    0
    0
    0
        Month 18: None; n=9, 5, 2
    0
    0
    0
        Month 18: Not Applicable; n=9, 5, 2
    4
    1
    0
        Month 21: Excellent; n=8, 5, 2
    4
    2
    2
        Month 21: Good; n=8, 5, 2
    0
    2
    0
        Month 21: Moderate; n=8, 5, 2
    0
    0
    0
        Month 21: None; n=8, 5, 2
    0
    0
    0
        Month 21: Not Applicable; n=8, 5, 2
    4
    1
    0
        Month 24: Excellent; n=6, 5, 2
    1
    3
    2
        Month 24: Good; n=6, 5, 2
    0
    1
    0
        Month 24: Moderate; n=6, 5, 2
    0
    0
    0
        Month 24: None; n=6, 5, 2
    0
    0
    0
        Month 24: Not Applicable; n=6, 5, 2
    5
    1
    0
        Month 27: Excellent; n=2, 4, 2
    0
    1
    1
        Month 27: Good; n=2, 4, 2
    1
    1
    1
        Month 27: Moderate; n=2, 4, 2
    0
    0
    0
        Month 27: None; n=2, 4, 2
    0
    0
    0
        Month 27: Not Applicable; n=2, 4, 2
    1
    2
    0
        Month 30: Excellent; n=1, 4, 2
    1
    0
    1
        Month 30: Good; n=1, 4, 2
    0
    2
    1
        Month 30: Moderate; n=1, 4, 2
    0
    0
    0
        Month 30: None; n=1, 4, 2
    0
    0
    0
        Month 30: Not Applicable; n=1, 4, 2
    0
    2
    0
        Month 32: Excellent; n=0, 4, 2
    0
    1
    2
        Month 32: Good; n=0, 4, 2
    0
    2
    0
        Month 32: Moderate; n=0, 4, 2
    0
    0
    0
        Month 32: None; n=0, 4, 2
    0
    0
    0
        Month 32: Not Applicable; n=0, 4, 2
    0
    1
    0
        Final Visit: Excellent; n=10, 6, 2
    6
    1
    2
        Final Visit: Good; n=10, 6, 2
    0
    2
    0
        Final Visit: Moderate; n=10, 6, 2
    0
    0
    0
        Final Visit: None; n=10, 6, 2
    0
    0
    0
        Final Visit: Not Applicable; n=10, 6, 2
    4
    3
    0
    Notes
    [2] - n=subjects with an assessment at respective time point.
    [3] - n=subjects with an assessment at respective time point.
    [4] - n=subjects with an assessment at respective time point.
    No statistical analyses for this end point

    Primary: Investigator's Assessment of Haemostatic Efficacy per Bleeding Event

    		 Close Top of page
    End point title
    		 Investigator's Assessment of Haemostatic Efficacy per Bleeding Event [5]
    End point description
    Investigator's subjective assessment of haemostatic efficacy of Biostate per non-surgical bleeding (NSB) event. The efficacy grading scale was as follows: excellent=haemostasis achieved/cessation of bleeding; good=slight oozing/partial but adequate control of bleeding, does not require additional product for unplanned treatment; moderate=moderate bleeding/moderate control of bleeding, required additional product for unplanned treatment; none=severe uncontrolled bleeding. Major bleeding event=one that involves any bleeding into a joint, muscle, or mucosal bleeds of the gastro-intestinal tract (excluding nasal or oral bleeding). All other bleeding events were classified as minor unless the Investigator assessment noted otherwise.
    End point type
    Primary
    End point timeframe
    Up to Week 32
    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: Descriptive data was collected per protocol and is reported.
    End point values
    		 Prophylaxis - Safety/Efficacy/Per-protocol Set On-demand - Safety/Efficacy/Per-protocol Set Prophylaxis and On-demand - Safety/Efficacy/Per-protocol Set
    Number of subjects analysed
    10 [6]
    7 [7]
    2 [8]
    Units: Number of events
        All NSB Events: Excellent; n=96, 77, 97
    70
    35
    62
        All NSB Events: Good; n=96, 77, 97
    24
    41
    35
        All NSB Events: Moderate; n=96, 77, 97
    2
    1
    0
        All NSB Events: None; n=96, 77, 97
    0
    0
    0
        Spontaneous NSB: Excellent; n=76, 73, 93
    56
    33
    61
        Spontaneous NSB: Good; n=76, 73, 93
    18
    39
    32
        Spontaneous NSB: Moderate; n=76, 73, 93
    2
    1
    0
        Spontaneous NSB: None; n=76, 73, 93
    0
    0
    0
        Trauma NSB: Excellent; n=19, 1, 4
    13
    1
    1
        Trauma NSB: Good; n=19, 1, 4
    6
    0
    3
        Trauma NSB: Moderate; n=19, 1, 4
    0
    0
    0
        Trauma NSB: None; n=19, 1, 4
    0
    0
    0
        Post-surgery NSB: Excellent; n=1, 3, 0
    1
    1
    0
        Post-surgery NSB: Good; n=1, 3, 0
    0
    2
    0
        Post-surgery NSB: Moderate; n=1, 3, 0
    0
    0
    0
        Post-surgery NSB: None; n=1, 3, 0
    0
    0
    0
        Major NSB: Excellent; n=12, 9, 6
    5
    6
    2
        Major NSB: Good; n=12, 9, 6
    7
    3
    4
        Major NSB: Moderate; n=12, 9, 6
    0
    0
    0
        Major NSB: None; n=12, 9, 6
    0
    0
    0
        Minor NSB: Excellent; n=84, 68, 91
    65
    29
    60
        Minor NSB: Good; n=84, 68, 91
    17
    38
    31
        Minor NSB: Moderate; n=84, 68, 91
    2
    1
    0
        Minor NSB: None; n=84, 68, 91
    0
    0
    0
        Joint NSB: Excellent; n=4, 6, 3
    2
    5
    1
        Joint NSB: Good; n=4, 6, 3
    2
    1
    2
        Joint NSB: Moderate; n=4, 6, 3
    0
    0
    0
        Joint NSB: None; n=4, 6, 3
    0
    0
    0
        Mucosal NSB: Excellent; n=84, 69, 91
    64
    29
    60
        Mucosal NSB: Good; n=84, 69, 91
    18
    39
    31
        Mucosal NSB: Moderate; n=84, 69, 91
    2
    1
    0
        Mucosal NSB: None; n=84, 69, 91
    0
    0
    0
        Muscle NSB: Excellent; n=3, 2, 3
    0
    1
    1
        Muscle NSB: Good; n=3, 2, 3
    3
    1
    2
        Muscle NSB: Moderate; n=3, 2, 3
    0
    0
    0
        Muscle NSB: None; n=3, 2, 3
    0
    0
    0
        Other NSB: Excellent; n=5, 0, 0
    4
    0
    0
        Other NSB: Good; n=5, 0, 0
    1
    0
    0
        Other NSB: Moderate; n=5, 0, 0
    0
    0
    0
        Other NSB: None; n=5, 0, 0
    0
    0
    0
    Notes
    [6] - n=NSB events treated with Biostate and with a haemostatic efficacy assessment.
    [7] - n=NSB events treated with Biostate and with a haemostatic efficacy assessment.
    [8] - n=NSB events treated with Biostate and with a haemostatic efficacy assessment.
    No statistical analyses for this end point

    Secondary: Overview of Treatment-emergent Adverse Events (TEAEs)

    		 Close Top of page
    End point title
    		 Overview of Treatment-emergent Adverse Events (TEAEs)
    End point description
    An adverse event (AE) is any untoward medical occurrence that does not necessarily have a causal relationship to the study product. A serious AE (SAE) was defined as any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalisation or prolongation of existing hospitalisation; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is another medically important condition. The intensity/severity of AEs was categorized as mild, moderate, or severe. The relationship of the AE to the study product was categorized as not related, unlikely, possibly, probably or definitely. AEs occurring after the first dose of study medication were considered treatment-emergent.
    End point type
    Secondary
    End point timeframe
    Day 1 up to a maximum duration of 32 months or until marketing approval of registration of Biostate, whichever occurred earlier, for countries in which Biostate was initially licensed; up to a maximum of 12 months for countries outside the EU.
    End point values
    		 Prophylaxis - Safety/Efficacy/Per-protocol Set On-demand - Safety/Efficacy/Per-protocol Set Prophylaxis and On-demand - Safety/Efficacy/Per-protocol Set
    Number of subjects analysed
    10
    7
    2
    Units: subjects
        At least 1 TEAE
    7
    7
    2
        At least 1 severe AE
    1
    1
    0
        At least 1 serious AE
    0
    3
    0
        At least 1 TEAE leading to IMP discontinuation
    0
    0
    0
        At least 1 TEAE leading to death
    0
    1
    0
    No statistical analyses for this end point

    Secondary: VWF and Factor VIII Inhibitors

    		 Close Top of page
    End point title
    		 VWF and Factor VIII Inhibitors
    End point description
    Number of subjects with a positive test result for VWF and FVIII inhibitors at each 3-monthly visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 32 and Final Visit (included in the corresponding 3-monthly period based on Final Visit date).
    End point values
    		 Prophylaxis - Safety/Efficacy/Per-protocol Set On-demand - Safety/Efficacy/Per-protocol Set Prophylaxis and On-demand - Safety/Efficacy/Per-protocol Set
    Number of subjects analysed
    10 [9]
    7 [10]
    2 [11]
    Units: subjects
        VWF inhibitor: Baseline; n=10, 7, 2
    0
    0
    0
        VWF inhibitor: Month 3; n=10, 7, 2
    0
    0
    0
        VWF inhibitor: Month 6; n=10, 7, 2
    0
    0
    0
        VWF inhibitor: Month 9; n=10, 7, 2
    0
    0
    0
        VWF inhibitor: Month 12; n=9, 7, 2
    0
    0
    0
        VWF inhibitor: Month 15; n=9, 5, 2
    0
    0
    0
        VWF inhibitor: Month 18; n=9, 5, 2
    0
    0
    0
        VWF inhibitor: Month 21; n=7, 5, 2
    0
    0
    0
        VWF inhibitor: Month 24; n=6, 5, 2
    0
    0
    0
        VWF inhibitor: Month 27; n=2, 4, 2
    0
    0
    0
        VWF inhibitor: Month 30; n=1, 4, 2
    0
    0
    0
        VWF inhibitor: Month 32; n=0, 4, 2
    0
    0
    0
        VWF inhibitor: Final Visit; n=10, 6, 2
    0
    0
    0
        FVIII inhibitor: Baseline; n=8, 7, 2
    0
    0
    0
        FVIII inhibitor: Month 3; n=10, 7, 2
    0
    0
    0
        FVIII inhibitor: Month 6; n=10, 7, 2
    0
    0
    0
        FVIII inhibitor: Month 9; n=10, 7, 2
    0
    0
    0
        FVIII inhibitor: Month 12; n=9, 7, 2
    0
    0
    0
        FVIII inhibitor: Month 15; n=9, 5, 2
    0
    0
    0
        FVIII inhibitor: Month 18; n=9, 5, 2
    0
    0
    0
        FVIII inhibitor: Month 21; n=7, 5, 2
    0
    0
    0
        FVIII inhibitor: Month 24; n=6, 5, 2
    0
    0
    0
        FVIII inhibitor: Month 27; n=2, 4, 2
    0
    0
    0
        FVIII inhibitor: Month 30; n=1, 4, 2
    0
    0
    0
        FVIII inhibitor: Month 32; n=0, 4, 2
    0
    0
    0
        FVIII inhibitor: Final Visit; n=10, 6, 2
    0
    0
    0
    Notes
    [9] - n=subjects with an available test result for the respective visit.
    [10] - n=subjects with an available test result for the respective visit.
    [11] - n=subjects with an available test result for the respective visit.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Day 1 up to a maximum duration of 32 months or until marketing approval of registration of Biostate, whichever occurred earlier, for countries in which Biostate was initially licensed; up to a maximum of 12 months for countries outside the EU.
    Adverse event reporting additional description
    Treatment-emergent AEs are presented (those occurring after the first dose of study medication).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.0
    Reporting groups
    Reporting group title
    Prophylaxis Arm
    Reporting group description
    		 Single bolus doses were administered intravenously as required to manage the subject's VWD. Subjects received Biostate on a regular basis 1-3 times per week as part of a prophylactic therapy regimen. Individual doses and regimen were determined by the investigator based on the subject’s clinical condition, previous FVIII / VWF concentrate requirements, response to therapy, body weight, and reason for usage.

    Reporting group title
    On-demand Arm
    Reporting group description
    		 Single bolus doses were administered intravenously as required to manage the stubject's VWD. Subjects received Biostate to treat a spontaneous or traumatic bleeding event, to provide haemostatic control during a surgical procedure. If subjects used Biostate for irregular prevention of bleedings this was recorded as “on-demand” treatment. Individual doses and regimen were determined by the investigator based on the subject’s clinical condition, previous FVIII / VWF concentrate requirements, response to therapy, body weight, and reason for usage.

    Reporting group title
    Prophylaxis and On-demand Arm
    Reporting group description
    		 Single bolus doses were administered intravenously as required to manage their VWD. Subjects received Biostate to treat a spontaneous or traumatic bleeding event, to provide haemostatic control during a surgical procedure, or on a regular basis 1-3 times per week as part of a prophylactic therapy regimen. If subjects used Biostate for irregular prevention of bleedings this was recorded as “on-demand” treatment. Individual doses were determined by the investigator based on the subject’s clinical condition, previous FVIII / VWF concentrate requirements, response to therapy, body weight, and reason for usage.

    Serious adverse events
    		 Prophylaxis Arm On-demand Arm Prophylaxis and On-demand Arm
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 7 (42.86%)
    0 / 2 (0.00%)
         number of deaths (all causes)
    0
    1
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cervix carcinoma stage 0
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastric ulcer
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Reproductive system and breast disorders
    Dysfunctional uterine bleeding
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Diabetes insipidus
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Prophylaxis Arm On-demand Arm Prophylaxis and On-demand Arm
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 10 (70.00%)
    5 / 7 (71.43%)
    2 / 2 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine cancer
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    7
    0
    0
    Injury
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    1
    0
    1
    Abdominal injury
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Head injury
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Limb injury
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Post-traumatic pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Road traffic accident
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Skeletal injury
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Traumatic haematoma
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Vascular disorders
    Essential hypertension
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    0
    Hypertension
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Hypertensive crisis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 7 (28.57%)
    0 / 2 (0.00%)
         occurrences all number
    0
    2
    0
    Post-traumatic headache
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    2
    3
    0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Influenza like illness
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    2
    1
    0
    Abdominal pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Diarrhoea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Duodenal ulcer
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 10 (30.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    0
    Bone pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Muscle haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    2
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 7 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    2
    0
    1
    Bronchitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    1
    Influenza
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    1
    1
    0
    Rhinitis
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Acute tonsillitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0
    Cystitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    2
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 7 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    0
    Streptococcal infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0
    Tonsillitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 7 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Sep 2010
    • Data recording by electronic case report form (eCRF). • Inclusion of height assessment at Day 1 Visit. • Inclusion of an interim analysis. • Addition of thrombogenicity markers for paediatric patients ≤12 years of age, who underwent surgery (request from Paul-Ehrlich-Institut for the paediatric study CSLT-BIO-08-52).
    12 May 2011
    • Correction of nominal VWF concentration. • Addition of study duration differentiation between Biostate-licensed and unlicensed countries.
    26 Sep 2011
    • Addition of thrombogenicity markers for all subjects who underwent surgery. • Additional exclusion criterion: “Participation in another clinical study was not allowed during the course of the requested clinical trial period with the exception of the studies CSLCT-BIO-08-52 or CSLCT-BIO-08-54”.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 14:08:24 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA