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    Clinical Trial Results:
    An open-label multicenter study to evaluate the safety and tolerability of higher infusion parameters of immune globulin subcutaneous (human), 20% liquid (Hizentra®) in subjects with primary immunodeficiency

    Summary
    EudraCT number
    		 2016-003799-33
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    14 Dec 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Jun 2019
    First version publication date
    16 Jun 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    IgPro20_4004
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03033745
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    CSL Behring LLC
    Sponsor organisation address
    1020 First Avenue, King of Prussia, United States, 19406
    Public contact
    Trial Registration Coordinator, CSL Behring LLC, 610 878-4000, clinicaltrials@cslbehring.com
    Scientific contact
    Trial Registration Coordinator, CSL Behring LLC, 610 878-4000, 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 Jan 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Dec 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to determine the responder rate at higher infusion parameters of IgPro20 under the following conditions: • Pump-Assisted: Volume per injection site of 25 mL, 40 mL, and 50 mL; • Pump-Assisted: Flow rate per injection site of 25 mL/h, 50 mL/h, 75 mL/h and 100 mL/h; • Manual Push (manual infusion using syringe without a pump): Flow rate per injection site of 30 mL/h, 60 mL/h, and 120 mL/h (0.5 mL/min, 1 mL/min, and 2 mL/min, correspondingly).
    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
    01 Feb 2017
    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
    United States: 40
    Country: Number of subjects enrolled
    Canada: 9
    Worldwide total number of subjects
    49
    EEA total number of subjects
    0
    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)
    6
    Adolescents (12-17 years)
    5
    Adults (18-64 years)
    35
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 55 subjects were screened. Of these, 49 subjects (including pediatric subjects ≤ 17 years of age and obese subjects with body mass index [BMI] of ≥30 kg/m2) with primary immune deficiency (PID) were enrolled and evaluated in the study.

    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
    		 IgPro20 (Pump-Assisted Volume Cohort)
    Arm description
    		 Weekly subcutaneous administration with maximum volumes per injection site of 25 mL up to 50 mL.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Hizentra [human normal immunoglobulin (subcutaneous)]
    Investigational medicinal product code
    Other name
    IgPro20
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A liquid formulation of normal human IgG at a concentration of 20% administered as a subcutaneous infusion at a dose prescribed by subject’s physician prior to study entry.

    Arm title
    		 IgPro20 (Pump Assisted Flow Rate Cohort)
    Arm description
    		 Weekly subcutaneous administration with maximum flow rates per injection site of 25 mL/h up to 100 mL/h.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Hizentra [human normal immunoglobulin (subcutaneous)]
    Investigational medicinal product code
    Other name
    IgPro20
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A liquid formulation of normal human IgG at a concentration of 20% administered as a subcutaneous infusion at a dose prescribed by subject’s physician prior to study entry.

    Arm title
    		 IgPro20 (Manual Push Flow Rate Cohort)
    Arm description
    		 Weekly (ie, 2-7 times per week) subcutaneous administration with maximum flow rates per injection site of 30 mL/h up to 120 mL/h.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Hizentra [human normal immunoglobulin (subcutaneous)]
    Investigational medicinal product code
    Other name
    IgPro20
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A liquid formulation of normal human IgG at a concentration of 20% administered as a subcutaneous infusion at a dose prescribed by subject’s physician prior to study entry.

    Number of subjects in period 1
    		IgPro20 (Pump-Assisted Volume Cohort) IgPro20 (Pump Assisted Flow Rate Cohort) IgPro20 (Manual Push Flow Rate Cohort)
    Started
    15
    18
    16
    Completed
    14
    17
    14
    Not completed
    1
    1
    2
         Consent withdrawn by subject
    -
    1
    -
         Adverse event, non-fatal
    1
    -
    1
         Protocol deviation
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    IgPro20 (Pump-Assisted Volume Cohort)
    Reporting group description
    		 Weekly subcutaneous administration with maximum volumes per injection site of 25 mL up to 50 mL.

    Reporting group title
    IgPro20 (Pump Assisted Flow Rate Cohort)
    Reporting group description
    		 Weekly subcutaneous administration with maximum flow rates per injection site of 25 mL/h up to 100 mL/h.

    Reporting group title
    IgPro20 (Manual Push Flow Rate Cohort)
    Reporting group description
    		 Weekly (ie, 2-7 times per week) subcutaneous administration with maximum flow rates per injection site of 30 mL/h up to 120 mL/h.

    Reporting group values
    		 IgPro20 (Pump-Assisted Volume Cohort) IgPro20 (Pump Assisted Flow Rate Cohort) IgPro20 (Manual Push Flow Rate Cohort) Total
    Number of subjects
    		 15 18 16 49
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 6 0 6
        Adolescents (12-17 years)
    		 0 4 1 5
        Adults (18-64 years)
    		 14 6 15 35
        From 65-84 years
    		 1 2 0 3
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 49.1 ( 14.18 ) 26.7 ( 24.52 ) 47.9 ( 13.28 ) -
    Gender categorical
    Units: Subjects
        Female
    		 9 10 10 29
        Male
    		 6 8 6 20

    End points

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    End points reporting groups
    Reporting group title
    IgPro20 (Pump-Assisted Volume Cohort)
    Reporting group description
    		 Weekly subcutaneous administration with maximum volumes per injection site of 25 mL up to 50 mL.

    Reporting group title
    IgPro20 (Pump Assisted Flow Rate Cohort)
    Reporting group description
    		 Weekly subcutaneous administration with maximum flow rates per injection site of 25 mL/h up to 100 mL/h.

    Reporting group title
    IgPro20 (Manual Push Flow Rate Cohort)
    Reporting group description
    		 Weekly (ie, 2-7 times per week) subcutaneous administration with maximum flow rates per injection site of 30 mL/h up to 120 mL/h.

    Subject analysis set title
    Safety Analysis Set (SAS)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The Safety Analysis Set (SAS) comprised all subjects in the Full Analysis Set who received ≥ 1 dose or a partial dose of IgPro20 in the study.

    Primary: Percentage of Responders (pump-assisted volume)(SAS)

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    End point title
    		 Percentage of Responders (pump-assisted volume)(SAS) [1] [2]
    End point description
    A responder is a subject within the Pump-Assisted Cohorts that performs at least 3 out of 4 valid infusions at a certain infusion parameter level (weekly volumes per injection site of 25-50 mL). The infusion parameter level was considered successful if percentage of responders was ≥ 33%.
    End point type
    Primary
    End point timeframe
    At the end of 4 weeks for each planned infusion volume.
    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 statistics were used for this primary endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump-Assisted Volume Cohort)
    Number of subjects analysed
    15 [3]
    Units: Percent
    number (not applicable)
        25 mL
    86.7
        40 mL
    73.3
        50 mL
    73.3
    Notes
    [3] - 25 mL (N=15), 40 mL (N=15), 50 mL (N=15)
    No statistical analyses for this end point

    Primary: Percentage of Responders (pump-assisted flow rate)(SAS)

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    End point title
    		 Percentage of Responders (pump-assisted flow rate)(SAS) [4] [5]
    End point description
    A responder is a subject within the Pump-Assisted Cohorts that performs at least 3 out of 4 valid infusions at a certain infusion parameter level (weekly flow rates per injection site of 25-100 mL/hour). The infusion parameter level was considered successful if percentage of responders was ≥ 33%.
    End point type
    Primary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [4] - 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 statistics were used for this primary endpoint.
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump Assisted Flow Rate Cohort)
    Number of subjects analysed
    18 [6]
    Units: Percent
    number (not applicable)
        25 mL/h
    77.8
        50 mL/h
    77.8
        75 mL/h
    66.7
        100 mL/h
    61.1
    Notes
    [6] - 25 mL/h (N=18), 50 mL/h (N=18), 75 mL/h (N=18), 100 mL/h (N=18)
    No statistical analyses for this end point

    Primary: Percentage of Responders (manual-push flow rate)(SAS)

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    End point title
    		 Percentage of Responders (manual-push flow rate)(SAS) [7] [8]
    End point description
    A responder within the Manual Push Cohort is a subject that performs a minimum number of valid infusions (ie, 5-17) during 4 weeks corresponding to a certain flow rate level ([ie, 2-7 times per week], flow rates per injection site of 30-120 mL/hour). The infusion parameter level was considered successful if percentage of responders was ≥ 33%.
    End point type
    Primary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were used for this primary endpoint.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Manual Push Flow Rate Cohort)
    Number of subjects analysed
    16 [9]
    Units: Percent
    number (not applicable)
        30 mL/h
    100.0
        60 mL/h
    100.0
        120 mL/h
    87.5
    Notes
    [9] - 30 mL/h (N=16), 60 mL/h (N=16), 120 mL/h (N=16)
    No statistical analyses for this end point

    Secondary: Rate of treatment-emergent adverse events (TEAEs) per infusion (pump-assisted volume)(SAS)

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    End point title
    		 Rate of treatment-emergent adverse events (TEAEs) per infusion (pump-assisted volume)(SAS) [10]
    End point description
    Adverse event rate per infusion = number of adverse events/total number of infusions prior to subject's start date of non-response. Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion volume.
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump-Assisted Volume Cohort)
    Number of subjects analysed
    15 [11]
    Units: AEs/infusion
    number (not applicable)
        25 mL (number of infusions = 60)
    0.183
        40 mL (number of infusions = 48)
    0.188
        50 mL (number of infusions = 44)
    0.023
    Notes
    [11] - 25 mL (N=15), 40 mL (N=12), 50 mL (N=11)
    No statistical analyses for this end point

    Secondary: Rate of TEAEs per infusion (pump-assisted flow rate)(SAS)

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    End point title
    		 Rate of TEAEs per infusion (pump-assisted flow rate)(SAS) [12]
    End point description
    Adverse event rate per infusion = number of adverse events/total number of infusions prior to subject's start date of non-response. Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump Assisted Flow Rate Cohort)
    Number of subjects analysed
    18 [13]
    Units: AEs/infusion
    number (not applicable)
        25 mL/h (number of infusions = 70)
    0.329
        50 mL/h (number of infusions = 55)
    0.255
        75 mL/h (number of infusions = 50)
    0.140
        100 mL/h (number of infusions = 47)
    0.085
    Notes
    [13] - 25 mL/h (N=18), 50 mL/h (N=14), 75 mL/h (N=13), 100 mL/h (N=12)
    No statistical analyses for this end point

    Secondary: Rate of TEAEs per infusion (manual-push flow rate)(SAS)

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    End point title
    		 Rate of TEAEs per infusion (manual-push flow rate)(SAS) [14]
    End point description
    Adverse event rate per infusion = number of adverse events/total number of infusions prior to subject's start date of non-response. Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Manual Push Flow Rate Cohort)
    Number of subjects analysed
    16 [15]
    Units: AEs/infusion
    number (not applicable)
        30 mL/h (number of infusions = 220)
    0.064
        60 mL/h (number of infusions = 208)
    0.111
        100 mL/h (number of infusions = 198)
    0.081
    Notes
    [15] - 30 mL/h (N=16), 60 mL/h (N=16), 120 mL/h (N=14)
    No statistical analyses for this end point

    Secondary: Rate of local TEAEs (pump-assisted volume)(SAS)

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    End point title
    		 Rate of local TEAEs (pump-assisted volume)(SAS) [16]
    End point description
    Local adverse event rate per infusion = number of local adverse events/total number of infusions prior to subject's start date of non-response. Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC (Not Elsewhere Classified)", "infusion site reactions", and "injection site reactions". Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion volume.
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump-Assisted Volume Cohort)
    Number of subjects analysed
    15 [17]
    Units: Local AEs/infusion
    number (not applicable)
        25 mL (number of infusions = 60)
    0.150
        40 mL (number of infusions = 48)
    0.063
        50 mL (number of infusions = 44)
    0.0
    Notes
    [17] - 25 mL (N=15), 40 mL (N=12), 50 mL (N=11)
    No statistical analyses for this end point

    Secondary: Rate of local TEAEs (pump-assisted flow rate)(SAS)

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    End point title
    		 Rate of local TEAEs (pump-assisted flow rate)(SAS) [18]
    End point description
    Local adverse event rate per infusion = number of local adverse events/total number of infusions prior to subject's start date of non-response. Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions". Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump Assisted Flow Rate Cohort)
    Number of subjects analysed
    18 [19]
    Units: Local AEs/infusion
    number (not applicable)
        25 mL/h (number of infusions = 70)
    0.286
        50 mL/h (number of infusions = 55)
    0.145
        75 mL/h (number of infusions = 50)
    0.040
        100 mL/h (number of infusions = 47)
    0.021
    Notes
    [19] - 25 mL/h (N=18), 50 mL/h (N=14), 75 mL/h (N=13), 100 mL/h (N=12)
    No statistical analyses for this end point

    Secondary: Rate of local TEAEs (manual-push flow rate)(SAS)

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    End point title
    		 Rate of local TEAEs (manual-push flow rate)(SAS) [20]
    End point description
    Local adverse event rate per infusion = number of local adverse events/total number of infusions prior to subject's start date of non-response. Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions". Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Manual Push Flow Rate Cohort)
    Number of subjects analysed
    16 [21]
    Units: Local AEs/infusion
    number (not applicable)
        30 mL/h (number of infusions = 220)
    0.027
        60 mL/h (number of infusions = 208)
    0.082
        120 mL/h (number of infusions = 198)
    0.025
    Notes
    [21] - 30 mL/h (N=16), 60 mL/h (N=16), 120 mL/h (N=14)
    No statistical analyses for this end point

    Secondary: Time to onset of local TEAEs (pump-assisted volume)(SAS)

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    End point title
    		 Time to onset of local TEAEs (pump-assisted volume)(SAS) [22]
    End point description
    Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions". Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion volume.
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump-Assisted Volume Cohort)
    Number of subjects analysed
    15 [23]
    Units: Days
    arithmetic mean (standard deviation)
        25 mL (number of local TEAEs = 9)
    1.3 ( 2.45 )
        40 mL (number of local TEAEs = 3)
    0 ( 0.0 )
    Notes
    [23] - 25 mL (N=15), 40 mL (N=12), 50 mL (N=11): no local TEAEs, hence mean (SD) could not be calculated.
    No statistical analyses for this end point

    Secondary: Time to onset of local TEAEs (pump-assisted flow rate)(SAS)

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    End point title
    		 Time to onset of local TEAEs (pump-assisted flow rate)(SAS) [24]
    End point description
    Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions". Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump Assisted Flow Rate Cohort)
    Number of subjects analysed
    18 [25]
    Units: Days
    arithmetic mean (standard deviation)
        25 mL/h (number of local TEAEs = 20)
    1.7 ( 2.94 )
        50 mL/h (number of local TEAEs = 8)
    0.0 ( 0.04 )
        75 mL/h (number of local TEAEs = 2)
    0 ( 0.0 )
    Notes
    [25] - 25 mL (N=18), 50 mL (N=14), 75 mL (N=13), 100 mL (N=12): mean(SD)=0(non-evaluable because events=1)
    No statistical analyses for this end point

    Secondary: Time to onset of local TEAEs (manual-push flow rate)(SAS)

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    End point title
    		 Time to onset of local TEAEs (manual-push flow rate)(SAS) [26]
    End point description
    Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions". Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Manual Push Flow Rate Cohort)
    Number of subjects analysed
    16 [27]
    Units: Days
    arithmetic mean (standard deviation)
        30 mL/h (number of local TEAEs = 6)
    0.2 ( 0.41 )
        60 mL/h (number of local TEAEs = 17)
    0.3 ( 0.59 )
        120 mL/h (number of local TEAEs = 5)
    0.2 ( 0.45 )
    Notes
    [27] - 30 mL (N=16), 60 mL (N=16), 120 mL (N=14)
    No statistical analyses for this end point

    Secondary: Intensity of local TEAEs (pump-assisted volume)(SAS)

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    End point title
    		 Intensity of local TEAEs (pump-assisted volume)(SAS) [28]
    End point description
    Mild = A type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate = A type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the subject. Severe = A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion volume.
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump-Assisted Volume Cohort)
    Number of subjects analysed
    15 [29]
    Units: Number of subjects
    number (not applicable)
        25 mL mild
    3
        25 mL moderate
    0
        25 mL severe
    0
        40 mL mild
    1
        40 mL moderate
    0
        40 mL severe
    0
        50 mL mild
    0
        50 mL moderate
    0
        50 mL severe
    0
    Notes
    [29] - 25 mL (N=15), 40 mL (N=12), 50 mL (N=11)
    No statistical analyses for this end point

    Secondary: Intensity of local TEAEs (pump-assisted flow rate)(SAS)

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    End point title
    		 Intensity of local TEAEs (pump-assisted flow rate)(SAS) [30]
    End point description
    Mild = A type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate = A type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the subject. Severe = A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump Assisted Flow Rate Cohort)
    Number of subjects analysed
    18 [31]
    Units: Number of subjects
    number (not applicable)
        25 mL/h mild
    4
        25 mL/h moderate
    2
        25 mL/h severe
    0
        50 mL/h mild
    3
        50 mL/h moderate
    0
        50 mL/h severe
    0
        75 mL/h mild
    1
        75 mL/h moderate
    0
        75 mL/h severe
    0
        100 mL/h mild
    0
        100 mL/h moderate
    0
        100 mL/h severe
    1
    Notes
    [31] - 25 mL (N=18), 50 mL (N=14), 75 mL (N=13), 100 mL (N=12)
    No statistical analyses for this end point

    Secondary: Intensity of local TEAEs (manual-push flow rate)(SAS)

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    End point title
    		 Intensity of local TEAEs (manual-push flow rate)(SAS) [32]
    End point description
    Mild = A type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate = A type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the subject. Severe = A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Manual Push Flow Rate Cohort)
    Number of subjects analysed
    16 [33]
    Units: Number of subjects
    number (not applicable)
        30 mL/h mild
    3
        30 mL/h moderate
    0
        30 mL/h severe
    0
        60 mL/h mild
    4
        60 mL/h moderate
    0
        60 mL/h severe
    0
        120 mL/h mild
    2
        120 mL/h moderate
    0
        120 mL/h severe
    0
    Notes
    [33] - 30 mL (N=16), 60 mL (N=16), 120 mL (N=14)
    No statistical analyses for this end point

    Secondary: Duration of local TEAEs (pump-assisted volume)(SAS)

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    End point title
    		 Duration of local TEAEs (pump-assisted volume)(SAS) [34]
    End point description
    Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions".
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion volume.
    Notes
    [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump-Assisted Volume Cohort)
    Number of subjects analysed
    15 [35]
    Units: Days
    arithmetic mean (standard deviation)
        25 mL
    2.2 ( 1.30 )
        40 mL
    2.7 ( 2.08 )
    Notes
    [35] - 25 mL (N=15), 40 mL (N=12), 50 mL (N=11): no local TEAEs, hence mean (SD) could not be calculated.
    No statistical analyses for this end point

    Secondary: Duration of local TEAEs (pump-assisted flow rate)(SAS)

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    End point title
    		 Duration of local TEAEs (pump-assisted flow rate)(SAS) [36]
    End point description
    Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions".
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump Assisted Flow Rate Cohort)
    Number of subjects analysed
    18 [37]
    Units: Days
    arithmetic mean (standard deviation)
        25 mL/h
    1.2 ( 0.37 )
        50 mL/h
    1.6 ( 0.92 )
        75 mL/h
    1.0 ( 0.00 )
    Notes
    [37] - 25 mL/h (N=18), 50 mL/h (N=14), 75 mL (N=13), 100 mL/h (N=12): mean (SD) = 1.0 (non-evaluable)
    No statistical analyses for this end point

    Secondary: Duration of local TEAEs (manual-push flow rate)(SAS)

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    End point title
    		 Duration of local TEAEs (manual-push flow rate)(SAS) [38]
    End point description
    Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions".
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Manual Push Flow Rate Cohort)
    Number of subjects analysed
    16 [39]
    Units: Days
    arithmetic mean (standard deviation)
        30 mL/h
    2.2 ( 2.86 )
        60 mL/h
    5.6 ( 12.91 )
        120 mL/h
    3.0 ( 2.12 )
    Notes
    [39] - 30 mL/h (N=16), 60 mL/h (N=16), 120 mL/h (N=14)
    No statistical analyses for this end point

    Secondary: Tolerability of infusions (pump-assisted volume)(SAS)

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    End point title
    		 Tolerability of infusions (pump-assisted volume)(SAS) [40]
    End point description
    Tolerability = number of infusions without severe local adverse events / total number of infusions. Severe = A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion volume.
    Notes
    [40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump-Assisted Volume Cohort)
    Number of subjects analysed
    15 [41]
    Units: Proportion
    number (not applicable)
        25 mL (number of infusions = 60)
    1.00
        40 mL (number of infusions = 48)
    1.00
        50 mL (number of infusions = 44)
    1.00
    Notes
    [41] - For this end point, is not the number of subjects but the number of infusions being analyzed.
    No statistical analyses for this end point

    Secondary: Tolerability of infusions (pump-assisted flow rate)(SAS)

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    End point title
    		 Tolerability of infusions (pump-assisted flow rate)(SAS) [42]
    End point description
    Tolerability = number of infusions without severe local adverse events / total number of infusions. Severe = A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Pump Assisted Flow Rate Cohort)
    Number of subjects analysed
    18 [43]
    Units: Proportion
    number (not applicable)
        25 mL/h (number of infusions = 70)
    1.00
        50 mL/h (number of infusions = 55)
    1.00
        75 mL/h (number of infusions = 50)
    1.00
        100 mL/h (number of infusions = 47)
    0.98
    Notes
    [43] - For this end point, is not the number of subjects but the number of infusions being analyzed.
    No statistical analyses for this end point

    Secondary: Tolerability of infusions (manual-push flow rate)(SAS)

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    End point title
    		 Tolerability of infusions (manual-push flow rate)(SAS) [44]
    End point description
    Tolerability = number of infusions without severe local adverse events / total number of infusions. Severe = A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Only events are included which start prior to subject's start date of non-response.
    End point type
    Secondary
    End point timeframe
    At the end of 4 weeks for each planned infusion flow rate.
    Notes
    [44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The arms were reported separately because the volumes and flow rates were different between the three arms.
    End point values
    		 IgPro20 (Manual Push Flow Rate Cohort)
    Number of subjects analysed
    16 [45]
    Units: Proportion
    number (not applicable)
        30 mL/h (number of infusions = 220)
    1.00
        60 mL/h (number of infusions = 208)
    1.00
        120 mL/h (number of infusions = 198)
    1.00
    Notes
    [45] - For this end point, is not the number of subjects but the number of infusions being analyzed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 17 weeks per participant
    Adverse event reporting additional description
    Only events are included which start prior to subject's start date of non-response.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    IgPro20 (pump-assisted volume) 25 mL
    Reporting group description
    		 -

    Reporting group title
    IgPro20 (pump-assisted volume) 40 mL
    Reporting group description
    		 -

    Reporting group title
    IgPro20 (pump-assisted volume) 50 mL
    Reporting group description
    		 -

    Reporting group title
    IgPro20 (pump-assisted flow rate) 25 mL/h
    Reporting group description
    		 -

    Reporting group title
    IgPro20 (pump-assisted flow rate) 50 mL/h
    Reporting group description
    		 -

    Reporting group title
    IgPro20 (pump-assisted flow rate) 75 mL/h
    Reporting group description
    		 -

    Reporting group title
    IgPro20 (pump-assisted flow rate) 100 mL/h
    Reporting group description
    		 -

    Reporting group title
    IgPro20 (manual push flow rate) 30 mL/h
    Reporting group description
    		 -

    Reporting group title
    IgPro20 (manual push flow rate) 60 mL/h
    Reporting group description
    		 -

    Reporting group title
    IgPro20 (manual push flow rate) 120 mL/h
    Reporting group description
    		 -

    Serious adverse events
    		 IgPro20 (pump-assisted volume) 25 mL IgPro20 (pump-assisted volume) 40 mL IgPro20 (pump-assisted volume) 50 mL IgPro20 (pump-assisted flow rate) 25 mL/h IgPro20 (pump-assisted flow rate) 50 mL/h IgPro20 (pump-assisted flow rate) 75 mL/h IgPro20 (pump-assisted flow rate) 100 mL/h IgPro20 (manual push flow rate) 30 mL/h IgPro20 (manual push flow rate) 60 mL/h IgPro20 (manual push flow rate) 120 mL/h
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 IgPro20 (pump-assisted volume) 25 mL IgPro20 (pump-assisted volume) 40 mL IgPro20 (pump-assisted volume) 50 mL IgPro20 (pump-assisted flow rate) 25 mL/h IgPro20 (pump-assisted flow rate) 50 mL/h IgPro20 (pump-assisted flow rate) 75 mL/h IgPro20 (pump-assisted flow rate) 100 mL/h IgPro20 (manual push flow rate) 30 mL/h IgPro20 (manual push flow rate) 60 mL/h IgPro20 (manual push flow rate) 120 mL/h
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 15 (26.67%)
    4 / 12 (33.33%)
    1 / 11 (9.09%)
    7 / 18 (38.89%)
    4 / 14 (28.57%)
    3 / 13 (23.08%)
    3 / 12 (25.00%)
    5 / 16 (31.25%)
    8 / 16 (50.00%)
    7 / 14 (50.00%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Hypotension
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    General disorders and administration site conditions
    Injection site swelling
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    2 / 18 (11.11%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    4
    0
    0
    3
    0
    0
    0
    1
    3
    1
    Injection site erythema
         subjects affected / exposed
    1 / 15 (6.67%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    3 / 18 (16.67%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    2
    0
    8
    0
    0
    0
    0
    3
    0
    Injection site pain
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    2 / 18 (11.11%)
    2 / 14 (14.29%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    1 / 16 (6.25%)
    2 / 16 (12.50%)
    1 / 14 (7.14%)
         occurrences all number
    2
    0
    0
    7
    5
    0
    1
    4
    4
    1
    Injection site extravasation
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site haemorrhage
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    0
    1
    0
    0
    Injection site mass
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site pruritus
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    2 / 18 (11.11%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    2
    2
    0
    0
    0
    2
    0
    Injection site bruising
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    2
    3
    Injection site discolouration
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Injection site reaction
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Gait inability
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Fatigue
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Immune system disorders
    Allergy to arthropod bite
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Dyspnoea
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Foot fracture
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    2 / 14 (14.29%)
    1 / 13 (7.69%)
    1 / 12 (8.33%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    1
    0
    0
    0
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    2 / 16 (12.50%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    1
    0
    Nausea
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    2 / 16 (12.50%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 18 (5.56%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Rash
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Renal and urinary disorders
    Hypertonic bladder
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Infections and infestations
    Bronchitis viral
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    1 / 18 (5.56%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    0
    0
    0
    0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Tinea infection
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 15 (0.00%)
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Herpes zoster
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 12 (8.33%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 18 (5.56%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Sinusitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Tooth abscess
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 18 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 12 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Feb 2017
    •Introduction section updated to include recent clinical trial data (safe infusion of SCIG at infusion flow rates of up to 60 mL/h/site). •Infusion frequency in the Manual Push Flow Rate Cohort changed from 5 to 7 infusions per week to 2 to 7 infusions per week. •Definition of responders modified to account for the changed infusion frequency in the Manual Push Flow Rate Cohort. •Use of Interactive Response Technology introduced for IgPro20 accountability. •The frequency of office visits changed from every 5 to 8 weeks to every 4 weeks. •Differential count added to the list of hematology assessments. •Window for Screening changed from “on Day −14 (± 2)” to “between Day −35 and −7”. •Description of “valid infusion” criteria modified to include more details.
    31 May 2017
    •Study design updated to permit subjects who were unable to tolerate the respective infusion parameter level to continue study participation at the individually tolerable infusion parameter level for the remaining study duration. •Time window for collection of blood for serum IgG trough levels (Day 1, End of Study Visit) changed from “30 minutes before next infusion” to “within approximately 1 hour before next infusion”. •Relevant safety sections were updated to state that subjects who discontinued without withdrawing consent were followed up by weekly phone calls by site personnel for the full duration of their planned study participation to collect AE information.
    02 Dec 2017
    •Definition of study population modified to clarify the number of enrolled pediatric and obese subjects as target number of enrolled subjects and not a minimum number of subjects. •Inclusion criterion 4 modified to define Primary Immunodeficiency by use of the International Union of Immunological Societies Expert Committee as additional reference. •Inclusion criterion 5 modified to clarify the required tolerated flow rate for the Pump Assisted Flow Rate Cohort during the month before Day 1 (allowable variance of 20% around the stated flow rate of 25 mL/h for constant pressure pumps). •Backup paper diary to be used when eDiary unavailable. •New section on reporting of unusual failure of efficacy was added to the Serious Event Reporting section to comply with Health Canada’s Food and Drug Regulations (for Canadian sites only). •Definition of Full Analysis Set modified to include eligible subjects who provided informed consent and underwent study procedures after Screening. •Planned study duration increased from 9 to 18 months.

    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
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    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.

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