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   43865   clinical trials with a EudraCT protocol, of which   7286   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:
    A multicenter, double-blind, randomized, placebo-controlled, parallel-arm study to investigate the efficacy and safety of subcutaneous administration of CSL312 (garadacimab) in the prophylactic treatment of hereditary angioedema

    Summary
    EudraCT number
    		 2020-000570-25
    Trial protocol
    		 DE   HU   NL   IT  
    Global end of trial date
    07 Jun 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Jun 2023
    First version publication date
    24 Jun 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CSL312_3001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04656418
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    CSL Behring
    Sponsor organisation address
    1020 First Avenue, King of Prussia, United States, 19406
    Public contact
    Trial Registration Coordinator, CSL Behring LLC, +1 610-878-4000, clinicaltrials@cslbehring.com
    Scientific contact
    Trial Registration Coordinator, CSL Behring LLC, +1 610-878-4000, clinicaltrials@cslbehring.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002726-PIP01-19
    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
    07 Jun 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jun 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study was to evaluate the efficacy and safety of subcutaneous (SC) administration of CSL312 (garadacimab) in the prophylactic treatment of hereditary angioedema.
    Protection of trial subjects
    This study was carried out in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines and standard operating procedures for clinical research and development at CSL Behring.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Jan 2021
    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
    Netherlands: 3
    Country: Number of subjects enrolled
    Germany: 15
    Country: Number of subjects enrolled
    Hungary: 2
    Country: Number of subjects enrolled
    Canada: 8
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    United States: 21
    Country: Number of subjects enrolled
    Japan: 6
    Worldwide total number of subjects
    64
    EEA total number of subjects
    20
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    6
    Adults (18-64 years)
    52
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects were enrolled at study centers in Canada, Germany, Hungary, Israel, Japan, Netherlands, and the United States from 27 January 2021 to 07 June 2022.

    Pre-assignment
    Screening details
    		 A total of 80 subjects were screened, of which 64 subjects were randomised and received the loading dose in the treatment period.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Data analyst, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 CSL312
    Arm description
    		 Subjects received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CSL312
    Investigational medicinal product code
    Other name
    Factor XIIa inhibitor monoclonal antibody, garadacimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A loading dose of 400 mg as two 200 mg injections in Month 1 along with 200 mg injections, once monthly from Months 2 to 6.

    Arm title
    		 Placebo
    Arm description
    		 Subjects received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A CSL312 matched loading dose of placebo as two injections in Month 1 along with CSL312 matched placebo injections, once monthly from Months 2 to 6.

    Number of subjects in period 1
    		CSL312 Placebo
    Started
    39
    25
    Completed
    38
    22
    Not completed
    1
    3
         Withdrawal by subject
    1
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    CSL312
    Reporting group description
    		 Subjects received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.

    Reporting group values
    		 CSL312 Placebo Total
    Number of subjects
    		 39 25 64
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 43.3 ( 17.45 ) 37.8 ( 12.80 ) -
    Gender categorical
    Units: Subjects
        Female
    		 24 14 38
        Male
    		 15 11 26
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 1 2 3
        Not Hispanic or Latino
    		 37 23 60
        Unknown or Not Reported
    		 1 0 1
    Race
    Units: Subjects
        Asian
    		 4 2 6
        Black or African American
    		 0 1 1
        Native Hawaiian or Other Pacific Islander
    		 1 0 1
        White
    		 33 22 55
        Other
    		 1 0 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    CSL312
    Reporting group description
    		 Subjects received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.

    Subject analysis set title
    CSL312 and Placebo Comparison Group
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    CSL312: Subjects received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6. Placebo: Subjects received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.

    Primary: Time-Normalised Number of Hereditary Angioedema (HAE) Attacks per Month During Treatment Period

    		 Close Top of page
    End point title
    		 Time-Normalised Number of Hereditary Angioedema (HAE) Attacks per Month During Treatment Period
    End point description
    Time-normalised number of HAE attacks per month during treatment was calculated per subject as: [number of HAE attacks / length of subject treatment in days] * 30.4375. ITT analysis set included all the randomised subjects who provided written informed consent and underwent study screening procedures. 'Number of subjects analysed’ indicates the number of subjects with data available for endpoint analysis.
    End point type
    Primary
    End point timeframe
    First injection up to 6 months
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39
    24
    Units: number of HAE attacks per month
        arithmetic mean (standard deviation)
    0.27 ( 0.683 )
    2.01 ( 1.341 )
    Statistical analysis title
    		 CSL312 vs Placebo
    Comparison groups
    CSL312 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 < 0.001 [2]
    Method
    		 Two-sided Wilcoxon test
    Confidence interval
    Notes
    [1] - Test for differences
    [2] - Compared the time-normalised number of HAE attacks in the active and placebo arms by using a two-sided Wilcoxon test (Hierarchical Testing H01) at alpha = 5%.

    Secondary: Percentage Change in the Time-Normalised Number of HAE Attacks per Month During the Treatment Period Compared to the Run-in Period

    		 Close Top of page
    End point title
    		 Percentage Change in the Time-Normalised Number of HAE Attacks per Month During the Treatment Period Compared to the Run-in Period
    End point description
    Percentage change in the time-normalised number of HAE attacks was calculated within a subject as: 100 * [1 – (time-normalised number of HAE attacks per month during treatment period / time-normalised number of HAE attacks per month during run-in period)]. Time-normalised number of HAE attacks per month during treatment period was calculated per subject as: [number of HAE attacks / length of subject treatment in days] * 30.4375. ITT analysis set included all the randomised subjects who provided written informed consent and underwent study screening procedures. 'Number of subjects analysed’ indicates the number of subjects with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of subjects with data available for analysis at the specified time point.
    End point type
    Secondary
    End point timeframe
    6 months, first 3-months and second 3-months of treatment period
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39
    24
    Units: percentage change in HAE attacks/month
    arithmetic mean (standard deviation)
        6 Months of Treatment (n=39, 24)
    90.67 ( 22.433 )
    20.21 ( 42.661 )
        First 3-months of Treatment (n=39, 24)
    91.10 ( 21.255 )
    18.89 ( 53.837 )
        Second 3-months of Treatment (n=39, 22)
    90.12 ( 25.624 )
    29.87 ( 55.529 )
    Statistical analysis title
    		 CSL312 vs Placebo
    Statistical analysis description
    6 Months of treatment
    Comparison groups
    CSL312 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    P-value
    		 < 0.001 [4]
    Method
    		 Two-sided Wilcoxon test
    Confidence interval
    Notes
    [3] - Test for differences
    [4] - Compared the time-normalised number of HAE attacks in the active and placebo arms by using a two-sided Wilcoxon test.

    Secondary: Time-Normalised Number of HAE Attacks per Month Requiring On-Demand Treatment

    		 Close Top of page
    End point title
    		 Time-Normalised Number of HAE Attacks per Month Requiring On-Demand Treatment
    End point description
    Time-normalised number of HAE attacks per month requiring on-demand treatment was calculated per subjects as: [number of HAE attacks requiring on-demand treatment / length of subject treatment in days] * 30.4375. ITT analysis set included all the randomised subjects who provided written informed consent and underwent study screening procedures. 'Number of subjects analysed’ indicates the number of subjects with data available for endpoint analysis. ‘Number analysed (n)’ indicates the total number of HAE attacks available for analysis at the specified time point.
    End point type
    Secondary
    End point timeframe
    6 months, first 3-months and second 3-months of treatment period
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39 [5]
    24 [6]
    Units: number of HAE attacks per month
    arithmetic mean (standard deviation)
        6 Months of Treatment (n=63, 264)
    0.23 ( 0.663 )
    1.86 ( 1.412 )
        First 3-months of Treatment (n=31, 144)
    0.24 ( 0.748 )
    1.76 ( 1.378 )
        Second 3-months of Treatment (n=32, 120)
    0.23 ( 0.610 )
    1.80 ( 1.626 )
    Notes
    [5] - Overall units analysed: 63 total number of HAE attacks
    [6] - Overall units analysed:264 total number of HAE attacks; 22 subjects for Second 3-months of treatment
    Statistical analysis title
    		 CSL312 vs Placebo
    Statistical analysis description
    6 Months of treatment
    Comparison groups
    CSL312 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [7]
    P-value
    		 < 0.001 [8]
    Method
    		 Two-sided Wilcoxon test
    Confidence interval
    Notes
    [7] - Test for differences
    [8] - Tested the differences between the active and placebo arms using a two-sided Wilcoxon test at alpha = 5%.
    Statistical analysis title
    		 CSL312 vs Placebo
    Statistical analysis description
    First 3-months of treatment
    Comparison groups
    CSL312 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [9]
    P-value
    		 < 0.001 [10]
    Method
    		 Two-sided Wilcoxon test
    Confidence interval
    Notes
    [9] - Test for differences
    [10] - Tested the differences between the active and placebo arms using a two-sided Wilcoxon test at alpha = 5%.
    Statistical analysis title
    		 CSL312 vs Placebo
    Statistical analysis description
    Second 3-months of treatment
    Comparison groups
    CSL312 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [11]
    P-value
    		 < 0.001 [12]
    Method
    		 Two-sided Wilcoxon test
    Confidence interval
    Notes
    [11] - Test for differences
    [12] - Tested the differences between the active and placebo arms using a two-sided Wilcoxon test at alpha = 5%.

    Secondary: Time-Normalised Number of Moderate or Severe HAE Attacks per Month

    		 Close Top of page
    End point title
    		 Time-Normalised Number of Moderate or Severe HAE Attacks per Month
    End point description
    Time-normalised number of moderate or severe HAE attacks per month during treatment period was calculated per subject as: [number of moderate or severe HAE attacks / length of subject treatment in days] * 30.4375. ITT analysis set included all the randomised subjects who provided written informed consent and underwent study screening procedures. 'Number of subjects analysed’ indicates the number of subjects with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of subjects with data available for analysis at the specified time point.
    End point type
    Secondary
    End point timeframe
    6 months, first 3-months and second 3-months of treatment period
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39 [13]
    24 [14]
    Units: number of HAE attacks per month
    arithmetic mean (standard deviation)
        6 Months of Treatment (n=39, 24)
    0.13 ( 0.296 )
    1.35 ( 1.166 )
        First 3-months of Treatment (n=39,24)
    0.12 ( 0.305 )
    1.25 ( 1.091 )
        Second 3-months of Treatment (n=39,22)
    0.13 ( 0.320 )
    1.24 ( 1.296 )
    Notes
    [13] - Overall Number of Units Analysed: 63 total number of HAE attacks
    [14] - Overall Number of Units Analysed: 264 total number of HAE attacks
    Statistical analysis title
    		 CSL312 vs Placebo
    Statistical analysis description
    6 Months of treatment
    Comparison groups
    CSL312 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [15]
    P-value
    		 < 0.001 [16]
    Method
    		 Two-sided Wilcoxon test
    Confidence interval
    Notes
    [15] - Test for differences
    [16] - Tested the differences between the active and placebo arms using a two-sided Wilcoxon test at alpha = 5%.
    Statistical analysis title
    		 CSL312 vs Placebo
    Statistical analysis description
    First 3-months of treatment
    Comparison groups
    CSL312 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [17]
    P-value
    		 < 0.001 [18]
    Method
    		 Two-sided Wilcoxon test
    Confidence interval
    Notes
    [17] - Test for differences
    [18] - Tested the differences between the active and placebo arms using a two-sided Wilcoxon test at alpha = 5%.
    Statistical analysis title
    		 CSL312 vs Placebo
    Statistical analysis description
    Second 3-months of treatment
    Comparison groups
    CSL312 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [19]
    P-value
    		 < 0.001 [20]
    Method
    		 Two-sided Wilcoxon test
    Confidence interval
    Notes
    [19] - Test for differences
    [20] - Tested the differences between the active and placebo arms using a two-sided Wilcoxon test at alpha = 5%

    Secondary: Time-Normalised Number of HAE Attacks per Month in the First 3-months and Second 3-months of Treatment Period

    		 Close Top of page
    End point title
    		 Time-Normalised Number of HAE Attacks per Month in the First 3-months and Second 3-months of Treatment Period
    End point description
    Time-normalised number of HAE attacks per month during treatment was calculated per subject as: [number of HAE attacks / length of subject treatment in days] * 30.4375. ITT analysis set included all the randomised subjects who provided written informed consent and underwent study screening procedures. 'Number of subjects analysed’ indicates the number of subjects with data available for endpoint analysis. ‘Number analysed (n)’ indicates the number of subjects with data available for analysis at the specified time point.
    End point type
    Secondary
    End point timeframe
    First 3-months and second 3-months of treatment period
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39
    24
    Units: number of HAE attacks per month
    arithmetic mean (standard deviation)
        First 3-months of Treatment (n=39, 24)
    0.26 ( 0.749 )
    1.97 ( 1.287 )
        Second 3-months of Treatment (n=39, 22)
    0.28 ( 0.652 )
    1.86 ( 1.603 )
    Statistical analysis title
    		 CSL312 vs Placebo
    Statistical analysis description
    First 3-months of treatment
    Comparison groups
    CSL312 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [21]
    P-value
    		 < 0.001 [22]
    Method
    		 Two-sided Wilcoxon test
    Confidence interval
    Notes
    [21] - Test for differences
    [22] - Tested the differences between the active and placebo arms using a two-sided Wilcoxon test at alpha = 5%.
    Statistical analysis title
    		 CSL312 vs Placebo
    Statistical analysis description
    Second 3-months of treatment
    Comparison groups
    CSL312 v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [23]
    P-value
    		 < 0.001 [24]
    Method
    		 Two-sided Wilcoxon test
    Confidence interval
    Notes
    [23] - Test for differences
    [24] - Tested the differences between the active and placebo arms using a two-sided Wilcoxon test at alpha = 5%.

    Secondary: Relative Difference in Means in the Time-Normalised Number of HAE Attacks per Month Between CSL312 to Placebo

    		 Close Top of page
    End point title
    		 Relative Difference in Means in the Time-Normalised Number of HAE Attacks per Month Between CSL312 to Placebo
    End point description
    Relative difference in means in time-normalised number of HAE attacks/month CSL312 to Placebo was calculated as: 100*[(mean time-normalised number of HAE attacks for CSL312 – mean time-normalised number of HAE attacks for placebo) / mean time-normalised number of HAE attacks for placebo]. Time-normalised number of HAE attacks/month during treatment was calculated per subject as:[number of HAE attacks /subject treatment length(days)]*30.4375. ITT analysis set included all the randomised subjects who provided written informed consent and underwent study screening procedures. 'Number of subjects analysed’= number of subjects with data available for endpoint analysis.'n'=number of subjects with data available for analysis at specified time point. As pre-specified in protocol and SAP, data was reported for subjects between CSL312 and Placebo comparison group.
    End point type
    Secondary
    End point timeframe
    6 months, first 3-months and second 3-months of treatment period
    End point values
    		 CSL312 and Placebo Comparison Group
    Number of subjects analysed
    63
    Units: number of HAE attacks per month
    arithmetic mean (confidence interval 95%)
        6 Months of Treatment
    -86.51 (-95.68 to -57.84)
        First 3-months of Treatment
    -86.64 (-95.87 to -56.76)
        Second 3-months of Treatment (n=61)
    -85.01 (-95.62 to -48.74)
    Attachments
    		 Relative Difference in Means in the Time-Normalise
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With a Response to Subject’s Global Assessment of Response to Therapy (SGART)

    		 Close Top of page
    End point title
    		 Percentage of Subjects With a Response to Subject’s Global Assessment of Response to Therapy (SGART)
    End point description
    SGART is a self-assessment by the subject and measures the subject’s overall treatment response to the investigational product using the following ratings: 0 (none: worse or no response at all, not acceptable), 1 (poor: very little response, not acceptable), 2 (fair: some response, acceptable but could be better), 3 (good: good response, acceptable), and 4 (excellent: excellent response, as good as can be imagined). ITT analysis set included all the randomised subjects who provided written informed consent and underwent study screening procedures. ‘Number of subjects analysed’ indicates the number of subjects with data available for endpoint analysis.
    End point type
    Secondary
    End point timeframe
    Up to 6 months
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    38
    24
    Units: percentage of subjects
    number (not applicable)
        None
    2.6
    41.7
        Poor
    7.9
    16.7
        Fair
    7.9
    8.3
        Good
    15.8
    20.8
        Excellent
    65.8
    12.5
    No statistical analyses for this end point

    Secondary: Number of Subjects With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI)

    		 Close Top of page
    End point title
    		 Number of Subjects With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI)
    End point description
    AE is any untoward medical occurrence in a subject administered with an investigational product which does not necessarily have a causal relationship with treatment, can be any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product, whether or not considered related to product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event. An AESI is an AE of scientific and medical concern specific to sponsor’s product or program, for which ongoing monitoring and rapid communication by investigator to sponsor is appropriate. Safety analysis set included all the randomised subjects who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 3 months after the last injection (approximately 8 months)
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39
    25
    Units: subjects
        AE
    25
    15
        SAE
    1
    0
        AESI
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With CSL312-induced Anti-CSL312 Antibodies

    		 Close Top of page
    End point title
    		 Number of Subjects With CSL312-induced Anti-CSL312 Antibodies
    End point description
    Safety analysis set included all the randomised subjects who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
    End point type
    Secondary
    End point timeframe
    Up to 8 months
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39
    25
    Units: subjects
    1
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs)

    		 Close Top of page
    End point title
    		 Number of Subjects With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs)
    End point description
    Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters. Safety analysis set included all the randomised subjects who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 3 months after the last injection (approximately 8 months)
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39
    25
    Units: subjects
    1
    2
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With at Least One AE, SAE, and AESI

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least One AE, SAE, and AESI
    End point description
    AE is any untoward medical occurrence in a subject administered with an investigational product which does not necessarily have a causal relationship with treatment, can be any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product, whether or not considered related to product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event. An AESI is an AE of scientific and medical concern specific to sponsor’s product or program, for which ongoing monitoring and rapid communication by investigator to sponsor is appropriate. Safety analysis set included all the randomised subjects who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 3 months after the last injection (approximately 8 months)
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39
    25
    Units: percentage of subjects
    number (not applicable)
        AE
    64.1
    60.0
        SAE
    2.6
    0
        AESI
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With CSL312-induced Anti-CSL312 Antibodies

    		 Close Top of page
    End point title
    		 Percentage of Subjects With CSL312-induced Anti-CSL312 Antibodies
    End point description
    Safety analysis set included all the randomised subjects who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
    End point type
    Secondary
    End point timeframe
    Up to 6 months
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39
    25
    Units: percentage of subjects
        number (not applicable)
    2.6
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs
    End point description
    Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters. Safety analysis set included all the randomised subjects who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 3 months after the last injection (approximately 8 months)
    End point values
    		 CSL312 Placebo
    Number of subjects analysed
    39
    25
    Units: percentage of subjects
        number (not applicable)
    2.6
    8.0
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug up to 3 months after the last injection (approximately 8 months)
    Adverse event reporting additional description
    Safety analysis set included all the randomised subjects who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    CSL312
    Reporting group description
    		 Subjects received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.

    Serious adverse events
    		 CSL312 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 25 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Congenital, familial and genetic disorders
    Hereditary angioedema
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 25 (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
    		 CSL312 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    17 / 39 (43.59%)
    12 / 25 (48.00%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 39 (7.69%)
    4 / 25 (16.00%)
         occurrences all number
    9
    4
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    5
    Injection site erythema
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 25 (8.00%)
         occurrences all number
    1
    2
    Pyrexia
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 25 (8.00%)
         occurrences all number
    1
    2
    Eye disorders
    Visual impairment
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Abdominal pain
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Nausea
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Pain in extremity
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    3
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 39 (10.26%)
    2 / 25 (8.00%)
         occurrences all number
    4
    2
    Nasopharyngitis
         subjects affected / exposed
    3 / 39 (7.69%)
    1 / 25 (4.00%)
         occurrences all number
    3
    1
    COVID-19
         subjects affected / exposed
    0 / 39 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    3
    Gastrointestinal infection
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Conjunctivitis
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Sinusitis
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0

    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-Mon Apr 29 04:38:55 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA