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   43857   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, randomized study to evaluate the long-term clinical safety and efficacy of subcutaneous administration of human plasma-derived C1-esterase inhibitor in the prophylactic treatment of hereditary angioedema.

    Summary
    EudraCT number
    		 2014-001054-42
    Trial protocol
    		 DE   GB   HU   CZ   ES   IT  
    Global end of trial date
    21 Sep 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 Apr 2018
    First version publication date
    05 Apr 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CSL830_3002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02316353
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    CSL Behring GmbH
    Sponsor organisation address
    Emil-von-Behring-Strasse 76, Marburg, Germany, 35041
    Public contact
    Trial Registration Coordinator, CSL Behring GmbH, clinicaltrials@cslbehring.com
    Scientific contact
    Trial Registration Coordinator, CSL Behring GmbH, 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
    09 Nov 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Sep 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the clinical safety of subcutaneously administered C1-INH in the long-term prophylactic treatment of hereditary angioedema (HAE).
    Protection of trial subjects
    This study was conducted in accordance with standards of Good Clinical Practice as defined by the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, ethical principles that have their origin in the Declaration of Helsinki, and applicable national and local regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Dec 2014
    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
    Australia: 3
    Country: Number of subjects enrolled
    Canada: 12
    Country: Number of subjects enrolled
    Israel: 14
    Country: Number of subjects enrolled
    United States: 54
    Country: Number of subjects enrolled
    Romania: 1
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Czech Republic: 4
    Country: Number of subjects enrolled
    Germany: 22
    Country: Number of subjects enrolled
    Hungary: 6
    Country: Number of subjects enrolled
    Italy: 4
    Worldwide total number of subjects
    126
    EEA total number of subjects
    43
    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)
    7
    Adults (18-64 years)
    106
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study enrolled patients who participated in prior Study 3001. Because subjects were enrolled into Study 3002 while Study 3001 was still ongoing, all subjects enrolled into Study 3002 were randomized to the treatment arms to eliminate premature unblinding. In addition, also naive subjects were screened and randomized.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 CSL830 (40)
    Arm description
    		 A low-volume dose of C1-INH (40 IU/kg) administered subcutaneously twice a week
    Arm type
    		 Experimental

    Investigational medicinal product name
    C1-esterase inhibitor
    Investigational medicinal product code
    Other name
    CSL830
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered subcutaneously twice a week

    Arm title
    		 CSL830 (60)
    Arm description
    		 A high-volume dose of C1-INH (60 IU/kg) administered subcutaneously twice a week
    Arm type
    		 Experimental

    Investigational medicinal product name
    C1-esterase inhibitor
    Investigational medicinal product code
    Other name
    CSL830
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered subcutaneously twice a week

    Number of subjects in period 1
    		CSL830 (40) CSL830 (60)
    Started
    63
    63
    Completed
    55
    55
    Not completed
    8
    8
         Consent withdrawn by subject
    6
    2
         Adverse event, non-fatal
    1
    3
         Pregnancy
    1
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    CSL830 (40)
    Reporting group description
    		 A low-volume dose of C1-INH (40 IU/kg) administered subcutaneously twice a week

    Reporting group title
    CSL830 (60)
    Reporting group description
    		 A high-volume dose of C1-INH (60 IU/kg) administered subcutaneously twice a week

    Reporting group values
    		 CSL830 (40) CSL830 (60) Total
    Number of subjects
    		 63 63 126
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 2 1 3
        Adolescents (12-17 years)
    		 3 4 7
        Adults (18-64 years)
    		 56 50 106
        From 65-84 years
    		 2 8 10
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 40.8 ± 14.96 40.3 ± 16.26 -
    Gender categorical
    Units: Subjects
        Female
    		 40 36 76
        Male
    		 23 27 50

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    CSL830 (40)
    Reporting group description
    		 A low-volume dose of C1-INH (40 IU/kg) administered subcutaneously twice a week

    Reporting group title
    CSL830 (60)
    Reporting group description
    		 A high-volume dose of C1-INH (60 IU/kg) administered subcutaneously twice a week

    Primary: Person-time Incidence Rates (subject-based)

    		 Close Top of page
    End point title
    		 Person-time Incidence Rates (subject-based) [1]
    End point description
    Subject-based Analysis for Person-Time Incidence Rate = (the total number of subjects who experienced the event during the respective treatment) / (the sum of the date each subject experienced the event – the subject’s start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
    End point type
    Primary
    End point timeframe
    Up to 146 weeks
    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: Only descriptive statistics were collected for this endpoint.
    End point values
    		 CSL830 (40) CSL830 (60)
    Number of subjects analysed
    63
    63 [2]
    Units: Rate/Year
    number (not applicable)
        AEs Leading to Premature Study Discontinuation
    0.01
    0.03
        Thromboembolic Events
    0.00
    0.01
        Anaphylaxis
    0.00
    0.00
        HAE Attacks Resulting in In-patient Hospitalizatio
    0.00
    0.00
        Solicited AEs Graded as Severe
    0.00
    0.00
        Related SAEs Other Than Specified Above
    0.00
    0.00
        Antibodies to C1-INH (Inhibitory + Non-inhibitory)
    0.06
    0.06
    Notes
    [2] - Actual n=70 because 7 subjects titrated up from the 40 IU/kg arm and will be displayed in both arms
    No statistical analyses for this end point

    Primary: Person-time Incidence Rates (event-based)

    		 Close Top of page
    End point title
    		 Person-time Incidence Rates (event-based) [3]
    End point description
    Event-based Analysis for Person-Time Incidence Rate = (the total number of events documented during the respective treatment) / (the sum of each subject’s end date – the subject’s start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
    End point type
    Primary
    End point timeframe
    Up to 146 weeks
    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: Only descriptive statistics were collected for this endpoint.
    End point values
    		 CSL830 (40) CSL830 (60)
    Number of subjects analysed
    63
    63 [4]
    Units: Rate/Year
    number (not applicable)
        AEs Leading to Premature Study Discontinuation
    0.01
    0.03
        Thromboembolic Events
    0.00
    0.01
        Anaphylaxis
    0.00
    0.00
        HAE Attacks Resulting in In-patient Hospitalizatio
    0.00
    0.00
        Solicited AEs Graded as Severe
    0.00
    0.00
        Related SAEs Other Than Specified Above
    0.00
    0.00
        Antibodies to C1-INH (Inhibitory + Non-inhibitory)
    0.06
    0.09
    Notes
    [4] - Actual n=70 because 7 subjects titrated up from the 40 IU/kg arm and will be displayed in both arms
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who have Solicited Adverse Events (AEs)

    		 Close Top of page
    End point title
    		 Percentage of Subjects Who have Solicited Adverse Events (AEs)
    End point description
    The number of subjects having at least 1 solicited local AE during a treatment were divided by the number of subjects in the corresponding treatment. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
    End point type
    Secondary
    End point timeframe
    Up to 146 weeks
    End point values
    		 CSL830 (40) CSL830 (60)
    Number of subjects analysed
    63
    63 [5]
    Units: Percent
        number (not applicable)
    55.6
    45.7
    Notes
    [5] - Actual n=70 because 7 subjects titrated up from the 40 IU/kg arm and will be displayed in both arms
    No statistical analyses for this end point

    Secondary: Percent of Injections Followed by at Least One Solicited Adverse Event

    		 Close Top of page
    End point title
    		 Percent of Injections Followed by at Least One Solicited Adverse Event
    End point description
    The percent of injections followed by at least one solicited adverse event. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
    End point type
    Secondary
    End point timeframe
    Up to 146 weeks
    End point values
    		 CSL830 (40) CSL830 (60)
    Number of subjects analysed
    63
    63 [6]
    Units: Percent of injections
        number (not applicable)
    6.3
    5.1
    Notes
    [6] - Actual n=70 because 7 subjects titrated up from the 40 IU/kg arm and will be displayed in both arms
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Become Seropositive for Human Immunodeficiency virus (HIV-1/-2), Hepatitis B virus, or Hepatitis C virus

    		 Close Top of page
    End point title
    		 Percentage of Subjects Who Become Seropositive for Human Immunodeficiency virus (HIV-1/-2), Hepatitis B virus, or Hepatitis C virus
    End point description
    Blood samples to be tested for HIV-1/-2, HBV, and HCV. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
    End point type
    Secondary
    End point timeframe
    Up to 146 weeks
    End point values
    		 CSL830 (40) CSL830 (60)
    Number of subjects analysed
    63
    63 [7]
    Units: Percent
        number (not applicable)
    0
    0
    Notes
    [7] - Actual n=70 because 7 subjects titrated up from the 40 IU/kg arm and will be displayed in both arms
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who Experience a Time-normalized HAE Attack Frequency of <1 HAE Attack per 4-Week Period

    		 Close Top of page
    End point title
    		 Percentage of Subjects who Experience a Time-normalized HAE Attack Frequency of <1 HAE Attack per 4-Week Period
    End point description
    The proportion of subjects with a time-normalized merged HAE attack frequency of < 1 HAE attack per 4-week period. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL830.
    End point type
    Secondary
    End point timeframe
    Up to 146 weeks
    End point values
    		 CSL830 (40) CSL830 (60)
    Number of subjects analysed
    63
    63
    Units: Percent
        number (not applicable)
    79.4
    85.7
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who are Responders

    		 Close Top of page
    End point title
    		 Percentage of Subjects who are Responders
    End point description
    A responder was defined as a subject with a ≥ 50% reduction in the time-normalized number of HAE attacks on CSL830 relative to the time-normalized number of HAE attacks used to qualify for participation in the current study. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL830.
    End point type
    Secondary
    End point timeframe
    Up to 146 weeks
    End point values
    		 CSL830 (40) CSL830 (60)
    Number of subjects analysed
    62
    60
    Units: Percent
        number (confidence interval 95%)
    93.5 (84.6 to 97.5)
    91.7 (81.9 to 96.4)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    146 weeks per subject
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    CSL830 (40)
    Reporting group description
    		 A low-volume dose of C1-INH (40 IU/kg) administered subcutaneously twice a week

    Reporting group title
    CSL830 (60)
    Reporting group description
    		 A high-volume dose of C1-INH (60 IU/kg) administered subcutaneously twice a week

    Serious adverse events
    		 CSL830 (40) CSL830 (60)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 63 (6.35%)
    5 / 70 (7.14%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Diffuse large B-cell lymphoma
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 CSL830 (40) CSL830 (60)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    33 / 63 (52.38%)
    28 / 70 (40.00%)
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    5 / 63 (7.94%)
    1 / 70 (1.43%)
         occurrences all number
    5
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    10 / 63 (15.87%)
    10 / 70 (14.29%)
         occurrences all number
    22
    19
    Migraine
         subjects affected / exposed
    4 / 63 (6.35%)
    0 / 70 (0.00%)
         occurrences all number
    8
    0
    General disorders and administration site conditions
    Injection site pain
         subjects affected / exposed
    17 / 63 (26.98%)
    10 / 70 (14.29%)
         occurrences all number
    211
    51
    Injection site erythema
         subjects affected / exposed
    10 / 63 (15.87%)
    12 / 70 (17.14%)
         occurrences all number
    45
    331
    Injection site bruising
         subjects affected / exposed
    9 / 63 (14.29%)
    7 / 70 (10.00%)
         occurrences all number
    56
    22
    Injection site reaction
         subjects affected / exposed
    5 / 63 (7.94%)
    8 / 70 (11.43%)
         occurrences all number
    75
    72
    Injection site haematoma
         subjects affected / exposed
    6 / 63 (9.52%)
    4 / 70 (5.71%)
         occurrences all number
    11
    12
    Injection site induration
         subjects affected / exposed
    4 / 63 (6.35%)
    3 / 70 (4.29%)
         occurrences all number
    19
    4
    Injection site swelling
         subjects affected / exposed
    4 / 63 (6.35%)
    2 / 70 (2.86%)
         occurrences all number
    19
    2
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    5 / 63 (7.94%)
    4 / 70 (5.71%)
         occurrences all number
    10
    14
    Diarrhoea
         subjects affected / exposed
    4 / 63 (6.35%)
    2 / 70 (2.86%)
         occurrences all number
    12
    2
    Toothache
         subjects affected / exposed
    1 / 63 (1.59%)
    4 / 70 (5.71%)
         occurrences all number
    1
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    6 / 63 (9.52%)
    5 / 70 (7.14%)
         occurrences all number
    6
    5
    Back pain
         subjects affected / exposed
    7 / 63 (11.11%)
    3 / 70 (4.29%)
         occurrences all number
    7
    4
    Myalgia
         subjects affected / exposed
    4 / 63 (6.35%)
    1 / 70 (1.43%)
         occurrences all number
    6
    6
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    12 / 63 (19.05%)
    21 / 70 (30.00%)
         occurrences all number
    23
    36
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 63 (12.70%)
    8 / 70 (11.43%)
         occurrences all number
    10
    10
    Urinary tract infection
         subjects affected / exposed
    3 / 63 (4.76%)
    6 / 70 (8.57%)
         occurrences all number
    4
    6
    Bronchitis
         subjects affected / exposed
    7 / 63 (11.11%)
    2 / 70 (2.86%)
         occurrences all number
    7
    2
    Sinusitis
         subjects affected / exposed
    4 / 63 (6.35%)
    4 / 70 (5.71%)
         occurrences all number
    4
    7

    More information

    		 Close Top of page

    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
    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-Wed Apr 24 19:51:32 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA