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    Clinical Trial Results:
    A Phase III Study to Evaluate the Efficacy, Safety, and Tolerability of Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (HYQVIA/HyQvia) and Immune Globulin Infusion (Human), 10% (GAMMAGARD LIQUID/KIOVIG) for the Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

    Summary
    EudraCT number
    		 2014-005496-87
    Trial protocol
    		 CZ   DK   DE   SE   GB   ES   NO   SK   GR   AT   PL   HR   IT  
    Global end of trial date
    23 Feb 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    05 May 2024
    First version publication date
    10 Mar 2023
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Global End of Trial Date updated

    Trial information

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    Trial identification
    Sponsor protocol code
    161403
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02549170
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    95 Hayden Avenue, Lexington, United States, MA 02421
    Public contact
    Study Director, Takeda, TrialDisclosures@takeda.com
    Scientific contact
    Study Director, Takeda, TrialDisclosures@takeda.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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    23 Feb 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Feb 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objective of the trial is to evaluate the efficacy of HYQVIA/HyQvia as a maintenance therapy for CIDP to prevent relapse of neuromuscular disability and impairment.
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Dec 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 4
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Czechia: 4
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Brazil: 6
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    Italy: 16
    Country: Number of subjects enrolled
    Denmark: 2
    Country: Number of subjects enrolled
    Norway: 1
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    Colombia: 5
    Country: Number of subjects enrolled
    Croatia: 1
    Country: Number of subjects enrolled
    Poland: 12
    Country: Number of subjects enrolled
    Serbia: 26
    Country: Number of subjects enrolled
    Turkey: 7
    Country: Number of subjects enrolled
    Slovakia: 3
    Country: Number of subjects enrolled
    Israel: 1
    Country: Number of subjects enrolled
    Ireland: 4
    Country: Number of subjects enrolled
    Mexico: 6
    Country: Number of subjects enrolled
    United States: 7
    Worldwide total number of subjects
    132
    EEA total number of subjects
    65
    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)
    0
    Adults (18-64 years)
    99
    From 65 to 84 years
    32
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants took part in the study at 54 investigative sites from December 15, 2015 to February 23, 2022. Participants with a diagnosis of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) were enrolled in this study.

    Pre-assignment
    Screening details
    		 Participants received HYQVIA/HyQvia or 0.25% albumin placebo solution with rHuPH20 (Recombinant Human Hyaluronidase) for 6 months or until relapse in Epoch 1, who relapsed during Epoch 1 received GGL/KIOVIG (non-US sites) or GAMUNEX-C (US sites) in Epoch 2. 138 participants were enrolled; 132 participants received atleast one dose of study drug.

    Period 1
    Period 1 title
    Epoch 1: Day 1 to Approximately 32 Weeks
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Epoch 1: Placebo with rHuPH20
    Arm description
    		 Participants received rHuPH20 80 U/10 mL solution, followed by SC placebo infusion at matching infusion volume as per the participant’s pre-randomization monthly equivalent IG dose when administered every 2, 3, or 4 weeks for 31.54 weeks or until relapse.
    Arm type
    		 Placebo

    Investigational medicinal product name
    0.25% albumin placebo solution with rHuPH20
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Participants received placebo solution (0.25% human albumin in Lactated Ringer's solution) and rHuPH20.

    Arm title
    		 Epoch 1: HYQVIA/HyQvia
    Arm description
    		 Participants received HYQVIA/HyQvia (rHuPH20) 80 U/g IG, followed by SC injection of immunoglobulin (IGI) 10% at the same monthly equivalent IG dose as per the individual participant’s pre-randomized IG dose when administered every 2, 3, or 4 weeks for 30.28 weeks or until relapse.
    Arm type
    		 Experimental

    Investigational medicinal product name
    HYQVIA
    Investigational medicinal product code
    Other name
    10%) with recombinant human hyaluronidase (rHuPH20), IGI, Immune Globulin Infusion 10% (Human) (IGI)
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Participants received HYQVIA/HyQvia SC which contains both Immune Globulin Infusion 10% (Human) (IGI, 10%) and recombinant human hyaluronidase (rHuPH20).

    Number of subjects in period 1
    		Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Started
    70
    62
    Completed
    46
    48
    Not completed
    24
    14
         Relapsed and did not Enter E2
    5
    2
         Did not Relapse;Ended Treatment (ET) From Epoch1
    2
    8
         Relapsed and Entered Epoch 2 (E2)
    17
    4
    Period 2
    Period 2 title
    Epoch 2: Up to Approximately Week 61
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG
    Arm description
    		 Participants who were enrolled to receive placebo with rHuPH20 and achieved chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse during Epoch 1 received the induction dose of GGL/KIOVIG 2 g/kg bi-weekly (BW), followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 25.63 weeks or until relapse.
    Arm type
    		 Experimental

    Investigational medicinal product name
    IGIV GAMMAGARD LIQUID/KIOVIG
    Investigational medicinal product code
    Other name
    Immune Globulin Infusion (Human), Intravenous immunoglobulin G, 10% (GAMMAGARD LIQUID/KIOVIG), GAMMAGARD LIQUID
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Participants received GAMMAGARD LIQUID/KIOVIG.

    Arm title
    		 Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG
    Arm description
    		 Participants who were enrolled to receive HYQVIA/HyQvia (rHuPH20) and achieved CIDP relapse during Epoch 1 received the induction dose of GGL/KIOVIG 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 28.67 weeks or until relapse.
    Arm type
    		 Experimental

    Investigational medicinal product name
    IGIV GAMMAGARD LIQUID/KIOVIG
    Investigational medicinal product code
    Other name
    Immune Globulin Infusion (Human), Intravenous immunoglobulin G, 10% (GAMMAGARD LIQUID/KIOVIG), GAMMAGARD LIQUID
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Participants received GAMMAGARD LIQUID/KIOVIG.

    Arm title
    		 Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Arm description
    		 Participants who were enrolled to receive placebo with rHuPH20 and achieved CIDP relapse during Epoch 1 received the induction dose of GAMMUNEX-C 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 24.33 weeks or until relapse.
    Arm type
    		 Experimental

    Investigational medicinal product name
    IGIV GAMUNEX®-C
    Investigational medicinal product code
    Other name
    Immune Globulin Infusion (Human), Intravenous immunoglobulin G, Approved IGIV product for US sites
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Participants received GAMUNEX®-C.

    Number of subjects in period 2 [1]
    		Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Started
    16
    4
    1
    Completed
    16
    4
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Epoch 2 included those participants from Epoch 1 who achieved CIDP relapse.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Epoch 1: Placebo with rHuPH20
    Reporting group description
    		 Participants received rHuPH20 80 U/10 mL solution, followed by SC placebo infusion at matching infusion volume as per the participant’s pre-randomization monthly equivalent IG dose when administered every 2, 3, or 4 weeks for 31.54 weeks or until relapse.

    Reporting group title
    Epoch 1: HYQVIA/HyQvia
    Reporting group description
    		 Participants received HYQVIA/HyQvia (rHuPH20) 80 U/g IG, followed by SC injection of immunoglobulin (IGI) 10% at the same monthly equivalent IG dose as per the individual participant’s pre-randomized IG dose when administered every 2, 3, or 4 weeks for 30.28 weeks or until relapse.

    Reporting group values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia Total
    Number of subjects
    		 70 62
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 53.9 ( 13.42 ) 55.0 ( 14.26 ) -
    Gender categorical
    Units: Subjects
        Female
    		 32 26 58
        Male
    		 38 36 74
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 2 1 3
        Asian
    		 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 0 0 0
        White
    		 64 58 122
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 4 3 7
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 14 9 23
        Not Hispanic or Latino
    		 46 47 93
        Unknown or Not Reported
    		 10 6 16

    End points

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    End points reporting groups
    Reporting group title
    Epoch 1: Placebo with rHuPH20
    Reporting group description
    		 Participants received rHuPH20 80 U/10 mL solution, followed by SC placebo infusion at matching infusion volume as per the participant’s pre-randomization monthly equivalent IG dose when administered every 2, 3, or 4 weeks for 31.54 weeks or until relapse.

    Reporting group title
    Epoch 1: HYQVIA/HyQvia
    Reporting group description
    		 Participants received HYQVIA/HyQvia (rHuPH20) 80 U/g IG, followed by SC injection of immunoglobulin (IGI) 10% at the same monthly equivalent IG dose as per the individual participant’s pre-randomized IG dose when administered every 2, 3, or 4 weeks for 30.28 weeks or until relapse.
    Reporting group title
    Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG
    Reporting group description
    		 Participants who were enrolled to receive placebo with rHuPH20 and achieved chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse during Epoch 1 received the induction dose of GGL/KIOVIG 2 g/kg bi-weekly (BW), followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 25.63 weeks or until relapse.

    Reporting group title
    Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG
    Reporting group description
    		 Participants who were enrolled to receive HYQVIA/HyQvia (rHuPH20) and achieved CIDP relapse during Epoch 1 received the induction dose of GGL/KIOVIG 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 28.67 weeks or until relapse.

    Reporting group title
    Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Reporting group description
    		 Participants who were enrolled to receive placebo with rHuPH20 and achieved CIDP relapse during Epoch 1 received the induction dose of GAMMUNEX-C 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 24.33 weeks or until relapse.

    Subject analysis set title
    Epoch 2: E1: Placebo Relapse - E2: IGIV
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who were enrolled to receive placebo with rHuPH20 and achieved CIDP relapse during Epoch 1 received the induction dose of GGL/KIOVIG or GAMMUNEX-C 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 25.63 weeks or until relapse.

    Subject analysis set title
    Epoch 2: E1: HYQVIA Relapse - E2: IGIV
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who were enrolled to receive HYQVIA/HyQvia (rHuPH20) and achieved CIDP relapse during Epoch 1 received the induction dose of GGL/KIOVIG 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 28.67 weeks or until relapse.

    Primary: Epoch 1: Relapse Rate

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    End point title
    		 Epoch 1: Relapse Rate
    End point description
    Relapse rate is defined as the percentage of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of >=1 point relative to the pre- subcutaneous (SC) treatment baseline score in 2 consecutive adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).
    End point type
    Primary
    End point timeframe
    Week 32 End of Epoch 1 Treatment (EOET1)/Unscheduled relapse visit assessment (UV)/Early Termination (ET)
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: percentage of participants
        number (confidence interval 95%)
    31.4 (21.76 to 43.03)
    9.7 (4.51 to 19.55)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Epoch 1: HYQVIA/HyQvia v Epoch 1: Placebo with rHuPH20
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0045
    Method
    		 Chi-squared
    Parameter type
    		 Newcombe confidence interval
    Point estimate
    -21.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -34.45
         upper limit
    		 -7.94

    Primary: Epoch 2: Responder Rate

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    End point title
    		 Epoch 2: Responder Rate [1]
    End point description
    Responder rate is defined as clinically meaningful improvement in functional ability defined as a decrease of >=1 point in the adjusted INCAT disability score at the completion of the intravenous (IV) treatment period [6 months] or at the last study visit of the IV treatment period, relative to the pre-IV treatment baseline score.
    End point type
    Primary
    End point timeframe
    Up to 6 Months post-Epoch 1 (End of Epoch 2 Treatment [EOE2T])/Unscheduled visit assessment (UV)/Early Termination
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis was performed for this endpoint.
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG
    Number of subjects analysed
    16
    Units: percentage of participants
        number (confidence interval 95%)
    100 (80.64 to 100.00)
    No statistical analyses for this end point

    Secondary: Epoch 1: Percentage of Participants Who Experience a Worsening of Functional Disability

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    End point title
    		 Epoch 1: Percentage of Participants Who Experience a Worsening of Functional Disability
    End point description
    Defined as one or more of the following: an increase of >=1 point relative to the pre-subcutaneous (SC) treatment baseline score in 2 consecutive adjusted Inflammatory Neuropathy Cause and Treatment disability scale (INCAT) scores; who experience CIDP worsening (defined as a >=8 kilo Pascal (kPa) decrease in the hand grip strength in the more affected hand); >=4 points decrease in raw Rasch-built Overall Disability Scale (R-ODS) relative to the pre-SC treatment baseline score (at the time of withdrawal from the SC treatment period). Participants are rounded off to nearest single decimal point.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    68
    56
    Units: percentage of participants
        number (confidence interval 95%)
    54.4 (42.66 to 65.70)
    37.5 (26.01 to 50.59)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Epoch 1: HYQVIA/HyQvia v Epoch 1: Placebo with rHuPH20
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0896 [2]
    Method
    		 Chi-squared corrected
    Parameter type
    		 Newcombe confidence interval
    Point estimate
    -16.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -33.02
         upper limit
    		 0.69
    Notes
    [2] - The treatment groups were compared using a continuity-corrected chi-square test.

    Secondary: Time to Relapse

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    End point title
    		 Time to Relapse
    End point description
    Time to relapse is defined as time from the date of the first SC administration of HYQVIA/HyQvia or placebo with rHuPH20 to the date of relapse. Participants who did not relapse were censored at their end of study.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: days
        median (full range (min-max))
    99 (20 to 221)
    99 (7 to 217)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Epoch 1: HYQVIA/HyQvia v Epoch 1: Placebo with rHuPH20
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002
    Method
    		 Wilcoxon Survival Test
    Confidence interval

    Secondary: Epoch 1: Number of Participants Experiencing Any Treatment-Emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs), Regardless of Causality

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    End point title
    		 Epoch 1: Number of Participants Experiencing Any Treatment-Emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs), Regardless of Causality
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an Investigational Product (IP) that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: participants
        Any TEAE
    40
    49
        Any Serious TEAE
    5
    2
    No statistical analyses for this end point

    Secondary: Epoch 1: Change From Pre-Subcutaneous (SC) Treatment Baseline in Rasch-built Overall Disability Scale (R-ODS)

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    End point title
    		 Epoch 1: Change From Pre-Subcutaneous (SC) Treatment Baseline in Rasch-built Overall Disability Scale (R-ODS)
    End point description
    The Rasch-Built Overall Disability Scale (R-ODS) is a participant self-reported, linearly-weighted overall disability scale that was specifically designed to capture activity and social participation limitations in participant with immune-mediated peripheral neuropathies including CIDP. The R-ODS is comprised of 24 items for which participants are asked to rate their functioning (ie, no difficulty, some difficulty, or could not do) related to a variety of everyday tasks at the moment of completion. The raw summed R-ODS score range is 0 to 48. The centile metric R-ODS score range is 0 to 100. The centile metric R-ODS score was used in the ANCOVA analysis. ANCOVA was used for the analysis.
    End point type
    Secondary
    End point timeframe
    Pre-subcutaneous (SC) treatment baseline, then weekly through Epoch 1 (approximately 7.3 months)
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    63
    59
    Units: score on a scale
        least squares mean (standard error)
    -6.1 ( 1.64 )
    -0.9 ( 1.69 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Epoch 1: HYQVIA/HyQvia v Epoch 1: Placebo with rHuPH20
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.03
    Method
    		 ANCOVA
    Parameter type
    		 Least Square Mean
    Point estimate
    5.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 9.9

    Secondary: Epoch 1: Number of Participants Experiencing Causally Related Serious and/or Non-Serious Adverse Events (SAEs and/or AEs)

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    End point title
    		 Epoch 1: Number of Participants Experiencing Causally Related Serious and/or Non-Serious Adverse Events (SAEs and/or AEs)
    End point description
    AE=any untoward medical occurrence in participant administered IP. AE can therefore be any unfavorable and unintended sign (e.g.,abnormal laboratory finding), symptom (e.g.,rash, pain, discomfort, fever, dizziness, etc.), disease (e.g.,peritonitis,bacteremia,etc.), outcome of death temporally associated with use of IP,considered causally related to the IP. SAE=untoward medical occurrence that at any dose meets following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization/results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is congenital anomaly/birth defect, is medically important event, thromboembolic events, hemolytic anemia. Non-SAE=AE not meeting this criteria. AE recorded by investigator as possibly/probably related to IP is considered related AE, any AE recorded as unlikely/not related is considered unrelated AE.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: participants
        Any IP-related TEAE
    19
    38
        Any Serious IP-related TEAE
    5
    1
    No statistical analyses for this end point

    Secondary: Epoch 1: Number of Participants With Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs

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    End point title
    		 Epoch 1: Number of Participants With Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs
    End point description
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: participants
        All AR/SAR
    27
    41
        Serious AR/SAR
    5
    1
    No statistical analyses for this end point

    Secondary: Epoch 1: Number of Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions

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    End point title
    		 Epoch 1: Number of Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions
    End point description
    AE=any untoward medical occurrence in participant administered IP.AE can therefore be any unfavorable and unintended sign(e.g.,abnormal laboratory finding),symptom(e.g.,rash,pain,discomfort,fever,dizziness,etc.), disease (e.g.,peritonitis,bacteremia,etc.),outcome of death temporally associated with use of IP, whether or not considered causally related to the IP.SAE=untoward medical occurrence that at any dose meets following criteria:outcome is fatal/results in death,is life-threatening,requires inpatient hospitalization/results in prolongation of an existing hospitalization,results in persistent or significant disability/incapacity,is congenital anomaly/birth defect,is medically important event, (e.g., thromboembolic events,hemolytic anemia).Non-SAE=AE not meeting this criteria.AE recorded by investigator as possibly/probably related to IP is considered related AE,any AE recorded as unlikely/not related is considered unrelated AE.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: causally related events in participants
    number (not applicable)
        Casually Related Non-serious Adverse Events
    53
    223
        Casually Related Serious Adverse Events
    5
    1
    No statistical analyses for this end point

    Secondary: Epoch 1: Number Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions Regardless of Causality

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    End point title
    		 Epoch 1: Number Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions Regardless of Causality
    End point description
    AE: any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. SAE: an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria. Participants can have more than one adverse event.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: events in participants
    number (not applicable)
        Non-serious AEs
    144
    340
        Serious AEs
    5
    2
    No statistical analyses for this end point

    Secondary: Epoch 1: Number Adverse Events (AEs) Temporally Associated With Infusions

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    End point title
    		 Epoch 1: Number Adverse Events (AEs) Temporally Associated With Infusions
    End point description
    AEs occurring during an infusion or within 72 hours after completion of an infusion. An AE is defined as any untoward medical occurrence in participant administered an Investigational Product (IP) that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. Participants can have more than one temporally associated with infusion adverse event.
    End point type
    Secondary
    End point timeframe
    During an infusion or within 72 hours after completion of an infusion post-Epoch 1
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: events in participants
        number (not applicable)
    61
    251
    No statistical analyses for this end point

    Secondary: Epoch 1: Number of Serious and/or Non-serious Adverse Reactions (ARs) plus Suspected ARs Associated With Infusions

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    End point title
    		 Epoch 1: Number of Serious and/or Non-serious Adverse Reactions (ARs) plus Suspected ARs Associated With Infusions
    End point description
    AR plus suspected AR: any AE that meets any of the criteria: AE considered by either investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following end of IP infusion, or AE for which causality assessment is missing or indeterminate. SAE: untoward medical occurrence that at any dose meets one or more of following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. Nonserious AE is AE that does not meet the criteria. Infusion per event = number of events / total number of infusions administered (started) to participants in analysis set. Participants can have more than one AR/suspected AR associated with infusion.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: events in participants
    number (not applicable)
        Non-Serious AR/Suspected AR
    76
    261
        Serious AR/Suspected AR
    5
    1
    No statistical analyses for this end point

    Secondary: Epoch 1: Number of Infusions in Participants for Which the Infusion Rate Was Reduced And/Or the Infusion Was Interrupted or Stopped Due to Intolerability And/Or Adverse Events (AEs)

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    End point title
    		 Epoch 1: Number of Infusions in Participants for Which the Infusion Rate Was Reduced And/Or the Infusion Was Interrupted or Stopped Due to Intolerability And/Or Adverse Events (AEs)
    End point description
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70 [3]
    62 [4]
    Units: number of infusions
        number (not applicable)
    1
    3
    Notes
    [3] - Units analysed is 647.
    [4] - Units analysed is 600.
    No statistical analyses for this end point

    Secondary: Epoch 1: Number of Treatment-emergent Systemic Adverse Events (AEs) Associated With Infusions

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    End point title
    		 Epoch 1: Number of Treatment-emergent Systemic Adverse Events (AEs) Associated With Infusions
    End point description
    A treatment-emergent adverse event (TEAE) is defined as any event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments. Participants can have more than one TEAE associated with infusion.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: events in participants
        number (not applicable)
    149
    342
    No statistical analyses for this end point

    Secondary: Epoch 1: Number Treatment-emergent Local Infusion Site Reactions Associated With Infusions

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    End point title
    		 Epoch 1: Number Treatment-emergent Local Infusion Site Reactions Associated With Infusions
    End point description
    AE=any untoward medical occurrence in participant administered an IP that does not have causal relationship with treatment. AE can be any unfavorable and unintended sign (e.g., abnormal laboratory finding), symptom (e.g., rash, pain, discomfort, fever, dizziness, etc.), disease (e.g., peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. Adverse reaction/suspected adverse reaction=AE that is considered by the investigator to be possibly or probably related to IP administration, or for which the causality is indeterminate or missing, or that begins during infusion of IP or within 72 hours following the end of IP infusion. Treatment-emergent adverse events (TEAEs) are defined as adverse events that occurred during or after administration of the first dose of IP. Infusion site adverse events and injection site adverse events refer to the same type of adverse events.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: events in participants
        number (not applicable)
    20
    141
    No statistical analyses for this end point

    Secondary: Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant

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    End point title
    		 Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. Data for number of events per participant is assessed as follows: Per participant = number of events / total number of participants in the safety analysis set.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: number of AEs/participant
    number (not applicable)
        Systemic AEs
    1.84
    3.24
        Local AEs
    0.29
    2.27
    No statistical analyses for this end point

    Secondary: Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Infusion

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    End point title
    		 Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Infusion
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. Data for number of events per infusion is assessed as follows: Per infusion = number of events / total number of infusions administered (started) to participants in the analysis set.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: number of AEs/infusion
    number (not applicable)
        Systemic Adverse Events
    0.20
    0.34
        Local Adverse Events
    0.03
    0.24
    No statistical analyses for this end point

    Secondary: Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion

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    End point title
    		 Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. An AE that is recorded by the investigator as possibly related or probably related to IP was considered a related AE, and any AE recorded as unlikely related or not related was considered unrelated AE.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: number of AEs/infusion
    number (not applicable)
        IP-Related Systemic TEAE
    0.06
    0.17
        IP-Related Local TEAE
    0.02
    0.21
    No statistical analyses for this end point

    Secondary: Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year

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    End point title
    		 Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. Data for number of events per 1000 participant-years is assessed as follows: Per 1000 participant-years = 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the safety analysis set, divided by 365.25)
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: number of AEs/1000 participant-year
    number (not applicable)
        Systemic AEs
    4689.22
    7341.52
        Local AEs
    727.01
    5150.02
    No statistical analyses for this end point

    Secondary: Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Participant

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    End point title
    		 Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Participant
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. An AE that is recorded by the investigator as possibly related or probably related to IP was considered a related AE, and any AE recorded as unlikely related or not related was considered unrelated AE.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: number of AEs/participant
    number (not applicable)
        IP-related Systemic TEAE
    0.54
    1.6
        IP-related Local TEAE
    0.21
    2
    No statistical analyses for this end point

    Secondary: Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events per Participant-year

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    End point title
    		 Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events per Participant-year
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. An AE that is recorded by the investigator as possibly related or probably related to IP was considered a related AE, and any AE recorded as unlikely related or not related was considered unrelated AE.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: number of AEs/1000 participant-year
    number (not applicable)
        IP-related Systemic TEAE
    1381.32
    3615.98
        IP-related Local TEAE
    545.26
    4529.1
    No statistical analyses for this end point

    Secondary: Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events per Infusion

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    End point title
    		 Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events per Infusion
    End point description
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Data for number of events per infusion is assessed as follows: Per infusion = number of events / total number of infusions administered (started) to participants in the analysis set.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: number of ARs/infusion
    number (not applicable)
        Systemic Plus Suspected ARs
    0.09
    0.20
        Local Plus Suspected ARs
    0.03
    0.24
    No statistical analyses for this end point

    Secondary: Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events per 1000 Participant-Year

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    End point title
    		 Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events per 1000 Participant-Year
    End point description
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Data for number of events per 1000 participant-years is assessed as follows: Per 1000 participant-years = 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the safety analysis set, divided by 365.25)
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: number of ARs/1000 Participant year
    number (not applicable)
        Systemic Plus Suspected ARs
    2035.63
    4383.00
        Local Plus Suspected ARs
    727.01
    5150.02
    No statistical analyses for this end point

    Secondary: Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events per Participant

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    End point title
    		 Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events per Participant
    End point description
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Data for number of events per participant is assessed as follows: Per participant = number of events / total number of participants in the safety analysis set.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: number of ARs/participant
    number (not applicable)
        Systemic Plus Suspected ARs
    0.80
    1.94
        Local Plus Suspected ARs
    0.29
    2.27
    No statistical analyses for this end point

    Secondary: Epoch 2: Number of Participants Experiencing Any Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs), Regardless of Causality

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    End point title
    		 Epoch 2: Number of Participants Experiencing Any Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs), Regardless of Causality
    End point description
    Number of participants experiencing any treatment-emergent serious and/or non-serious adverse events regardless of causality in Epoch 2 was reported.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: participants
        Any IP related TEAE
    11
    3
    1
        Any IP related serious TEAE
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 1: Number of Participants Who Develop Binding and/or Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20)

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    End point title
    		 Epoch 1: Number of Participants Who Develop Binding and/or Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20)
    End point description
    Number of participants who developed binding and/or neutralizing antibodies to rHuPH20 in Epoch 1 were reported. High-binding antibodies is defined as number of participants who had at least one anti-rHuPH20 antibody titer ≥1:160 during treatment.
    End point type
    Secondary
    End point timeframe
    Week 32 (EOET1)/UV/ET
    End point values
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia
    Number of subjects analysed
    70
    62
    Units: participants
    1
    7
    No statistical analyses for this end point

    Secondary: Epoch 2: Number of Participants with Serious and/or Non-serious Adverse Reactions (ARs) plus Suspected ARs

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    End point title
    		 Epoch 2: Number of Participants with Serious and/or Non-serious Adverse Reactions (ARs) plus Suspected ARs
    End point description
    An adverse reaction/suspected adverse reaction is defined as an Adverse Event that is considered by the investigator to be possibly or probably related to IP administration, or for which the causality is indeterminate or missing, or that begins during infusion of IP or within 72 hours following the end of IP infusion.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: participants
        Any AR/SAR
    10
    3
    0
        Any Serious AR/SAR
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Number of Participants Experiencing Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs)

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    End point title
    		 Epoch 2: Number of Participants Experiencing Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs)
    End point description
    AE=any untoward medical occurrence in participant administered IP.AE can therefore be any unfavorable and unintended sign(e.g.,abnormal laboratory finding),symptom(e.g.,rash,pain,discomfort,fever,dizziness,etc.), disease (e.g.,peritonitis,bacteremia,etc.),outcome of death temporally associated with use of IP, whether or not considered causally related to the IP.SAE=untoward medical occurrence that at any dose meets following criteria:outcome is fatal/results in death,is life-threatening,requires inpatient hospitalization/results in prolongation of an existing hospitalization,results in persistent or significant disability/incapacity,is congenital anomaly/birth defect,is medically important event, (e.g., thromboembolic events,hemolytic anemia).Non-SAE=AE not meeting this criteria.AE recorded by investigator as possibly/probably related to IP is considered related AE,any AE recorded as unlikely/not related is considered unrelated AE.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: participants
        Causally related AEs
    8
    3
    0
        Causally related SAEs
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Number of Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions Regardless of Causality

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    End point title
    		 Epoch 2: Number of Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions Regardless of Causality
    End point description
    A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria. An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Participants can have more than one adverse event.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: events in participants
    number (not applicable)
        Serious AEs
    0
    0
    0
        Non-serious AEs
    35
    25
    1
    No statistical analyses for this end point

    Secondary: Epoch 2: Number of Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions

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    End point title
    		 Epoch 2: Number of Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions
    End point description
    AE=any untoward medical occurrence in participant administered IP.AE can therefore be any unfavorable and unintended sign(e.g.,abnormal laboratory finding),symptom(e.g.,rash,pain,discomfort,fever,dizziness,etc.), disease (e.g.,peritonitis,bacteremia,etc.),outcome of death temporally associated with use of IP, whether or not considered causally related to the IP.SAE=untoward medical occurrence that at any dose meets following criteria:outcome is fatal/results in death,is life-threatening,requires inpatient hospitalization/results in prolongation of an existing hospitalization,results in persistent or significant disability/incapacity,is congenital anomaly/birth defect,is medically important event, (e.g.; thromboembolic events,hemolytic anemia).Non-SAE=AE not meeting this criteria.AE recorded by investigator as possibly/probably related to IP is considered related AE,any AE recorded as unlikely/not related is considered unrelated AE.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: events in participants
    number (not applicable)
        Any TEAE
    23
    0
    0
        Any serious TEAE
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Number of Adverse Events (AEs) Temporally Associated With Infusions

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    End point title
    		 Epoch 2: Number of Adverse Events (AEs) Temporally Associated With Infusions
    End point description
    AEs occurring during an infusion or within 72 hours after completion of an infusion. An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. Participants can have more than one adverse event.
    End point type
    Secondary
    End point timeframe
    During an infusion or within 72 hours after completion of an infusion post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: events in participants
        number (not applicable)
    25
    11
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Number of Serious and/or Non-serious Adverse Reactions (ARs) plus Suspected ARs Associated With Infusions

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    End point title
    		 Epoch 2: Number of Serious and/or Non-serious Adverse Reactions (ARs) plus Suspected ARs Associated With Infusions
    End point description
    A SAE is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event, thromboembolic events, hemolytic anemia. A nonserious AE is an AE that does not meet the criteria. An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Participants can have more than one AR/SAR.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: events in participants
        number (not applicable)
    28
    11
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Number of Treatment-emergent Local Infusion Site Reactions Associated With Infusions

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    End point title
    		 Epoch 2: Number of Treatment-emergent Local Infusion Site Reactions Associated With Infusions
    End point description
    AE=any untoward medical occurrence in participant administered an IP that does not have causal relationship with treatment. AE can be any unfavorable and unintended sign (e.g., abnormal laboratory finding), symptom (e.g., rash, pain, discomfort, fever, dizziness, etc.), disease (e.g., peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. Adverse reaction/suspected adverse reaction=AE that is considered by the investigator to be possibly or probably related to IP administration, or for which the causality is indeterminate or missing, or that begins during infusion of IP or within 72 hours following the end of IP infusion. TEAEs are defined as adverse events that occurred during or after administration of the first dose of IP. Infusion site adverse events and injection site adverse events refer to the same type of adverse events.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: events in participants
        number (not applicable)
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Number of Treatment-emergent Systemic Adverse Events (AEs) Associated With Infusions

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    End point title
    		 Epoch 2: Number of Treatment-emergent Systemic Adverse Events (AEs) Associated With Infusions
    End point description
    A treatment-emergent adverse event (TEAE) is defined as any event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments. Participants can have more than one treatment-emergent systemic AEs.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: events in participants
        number (not applicable)
    35
    25
    1
    No statistical analyses for this end point

    Secondary: Epoch 2: Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Intolerability and/or Adverse Events (AEs)

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    End point title
    		 Epoch 2: Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Intolerability and/or Adverse Events (AEs)
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG
    Number of subjects analysed
    16 [5]
    4 [6]
    Units: number of infusions
        number (not applicable)
    1
    1
    Notes
    [5] - Number of infusion is 328.
    [6] - Number of infusion is 61.
    No statistical analyses for this end point

    Secondary: Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Infusion

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    End point title
    		 Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Infusion
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: number of AEs/infusion
    number (not applicable)
        Systemic AEs
    0.11
    0.41
    0.06
        Local AEs
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant

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    End point title
    		 Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: number of AEs/participant
    number (not applicable)
        Systemic AEs
    2.19
    6.25
    1.00
        Local AEs
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year

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    End point title
    		 Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: number of AEs/1000 participant-year
    number (not applicable)
        Systemic AEs
    4645.26
    12806.80
    2135.96
        Local AEs
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion

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    End point title
    		 Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. An AE that is recorded by the investigator as possibly related or probably related to IP was considered a related AE, and any AE recorded as unlikely related or not related was considered unrelated AE.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: number of AEs/infusion
    number (not applicable)
        IP-related Systemic Adverse Events
    0.07
    0.13
    0
        IP-related Local Adverse Events
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant

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    End point title
    		 Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. An AE that is recorded by the investigator as possibly related or probably related to IP was considered a related AE, and any AE recorded as unlikely related or not related was considered unrelated AE.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: number of AEs/participant
    number (not applicable)
        IP-related Systemic Adverse Events
    1.44
    2
    0
        IP-related Local Adverse Events
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant-Year

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    End point title
    		 Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant-Year
    End point description
    An AE is defined as any untoward medical occurrence in participant administered an IP that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an IP, whether or not considered causally related to the IP. An AE that is recorded by the investigator as possibly related or probably related to IP was considered a related AE, and any AE recorded as unlikely related or not related was considered unrelated AE.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: number of AEs/1000 participant-year
    number (not applicable)
        IP-related Systemic Adverse Events
    3052.6
    4098.18
    0
        IP-related Local Adverse Events
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected Ars, Expressed as Number of Events Per Infusion

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    End point title
    		 Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected Ars, Expressed as Number of Events Per Infusion
    End point description
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Data for number of events per infusion is assessed as follows: Per infusion = number of events / total number of infusions administered (started) to participants in the analysis set.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: number of ARs/infusion
    number (not applicable)
        Systemic plus Suspected ARs
    0.09
    0.18
    0
        Local plus Suspected ARs
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events Per Participant

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    End point title
    		 Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events Per Participant
    End point description
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Data for number of events per participant is assessed as follows: Per participant = number of events / total number of participants in the safety analysis set.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: number of ARs/participant
    number (not applicable)
        Systemic plus Suspected ARs
    1.75
    2.75
    0
        Local plus Suspected ARs
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Epoch 2: Percentage of Participants With Clinically Meaningful Improvement in Functional Ability

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    End point title
    		 Epoch 2: Percentage of Participants With Clinically Meaningful Improvement in Functional Ability
    End point description
    Defined as one or more of the following: a decrease of >=1 point in the adjusted Inflammatory Neuropathy Cause and Treatment disability scale (INCAT) score at 2 consecutive time points; who experience CIDP improvement (defined as ≥8 kilo Pascal (kPa) increase in hand grip strength in the more affected hand; >=4 points increase in Rasch-built Overall Disability Scale (R-ODS)) at the completion of the intravenous (IV) treatment period [6 months] or at the last study visit of the IV treatment period, relative to the pre-IV treatment baseline score.
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: IGIV Epoch 2: E1: HYQVIA Relapse - E2: IGIV
    Number of subjects analysed
    17
    4
    Units: percentage of participants
        number (not applicable)
    100
    100
    No statistical analyses for this end point

    Secondary: Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events Per 1000 Participant-Year

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    End point title
    		 Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) plus Suspected ARs, Expressed as Number of Events Per 1000 Participant-Year
    End point description
    An AR plus suspected AR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 h following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Data for number of events per 1000 participant-years is assessed as follows: Per 1000 participant-years = 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the safety analysis set, divided by 365.25)
    End point type
    Secondary
    End point timeframe
    Throughout Epoch 2, up to 6 months post-Epoch 1
    End point values
    		 Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Number of subjects analysed
    16
    4
    1
    Units: number of ARs/1000 participant-year
    number (not applicable)
        Systemic plus Suspected ARs
    3716.21
    5634.99
    0
        Local plus Suspected ARs
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the date of signing of the informed consent form up to the end of the study, approximately 74 months.
    Adverse event reporting additional description
    Epoch 1 safety analysis set included all participants who received any study treatment. Epoch 2 safety analysis set included all participants who had a relapse in Epoch 1, entered Epoch 2, and received IGIV treatment with either GGL/KIOVIG or GAMUNEX-C.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Epoch 1: Placebo with rHuPH20
    Reporting group description
    		 Participants received rHuPH20 80 U/10 mL solution, followed by SC placebo infusion at matching infusion volume as per the participant’s pre-randomization monthly equivalent IG dose when administered every 2, 3, or 4 weeks for 30.28 weeks or until relapse.

    Reporting group title
    Epoch 1: HYQVIA/HyQvia
    Reporting group description
    		 Participants received HYQVIA/HyQvia (rHuPH20) 80 U/g IG, followed by SC injection of immunoglobulin (IGI) 10% at the same monthly equivalent IG dose as per the individual participant’s pre-randomized IG dose when administered every 2, 3, or 4 weeks for 31.54 weeks or until relapse.

    Reporting group title
    Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C
    Reporting group description
    		 Participants who were enrolled to receive placebo with rHuPH20 and achieved CIDP relapse during Epoch 1 received the induction dose of GAMMUNEX-C 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 24.33 weeks or until relapse.

    Reporting group title
    Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG
    Reporting group description
    		 Participants who were enrolled to receive HYQVIA/HyQvia (rHuPH20) and achieved CIDP relapse during Epoch 1 received the induction dose of GGL/KIOVIG 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 28.67 weeks or until relapse.

    Reporting group title
    Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG
    Reporting group description
    		 Participants who were enrolled to receive placebo with rHuPH20 and achieved CIDP relapse during Epoch 1 received the induction dose of GGL/KIOVIG 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as per the participant’s pre-randomization IGIV dosing regimen when administered every 3 weeks for 25.63 weeks or until relapse.

    Serious adverse events
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 70 (7.14%)
    2 / 62 (3.23%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 62 (1.61%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic inflammatory demyelinating polyradiculoneuropathy
         subjects affected / exposed
    4 / 70 (5.71%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Otitis media chronic
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 62 (1.61%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Epoch 1: Placebo with rHuPH20 Epoch 1: HYQVIA/HyQvia Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    19 / 70 (27.14%)
    42 / 62 (67.74%)
    1 / 1 (100.00%)
    3 / 4 (75.00%)
    11 / 16 (68.75%)
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 70 (1.43%)
    4 / 62 (6.45%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    10
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    8 / 70 (11.43%)
    8 / 62 (12.90%)
    0 / 1 (0.00%)
    2 / 4 (50.00%)
    6 / 16 (37.50%)
         occurrences all number
    17
    25
    0
    8
    22
    Dizziness
         subjects affected / exposed
    1 / 70 (1.43%)
    4 / 62 (6.45%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    5
    0
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 62 (1.61%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    2
    0
    0
    1
    Migraine
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    0
    1
    Tremor
         subjects affected / exposed
    0 / 70 (0.00%)
    2 / 62 (3.23%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    2
    0
    0
    1
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 62 (1.61%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    0
    0
    1
    Anaemia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    0
    0
    0
    1
    Neutropenia
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 62 (1.61%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    0
    0
    1
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    0
    1
    Chills
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 62 (1.61%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    Fatigue
         subjects affected / exposed
    2 / 70 (2.86%)
    6 / 62 (9.68%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    2
    9
    0
    0
    1
    Illness
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    0
    1
    Infusion site erythema
         subjects affected / exposed
    0 / 70 (0.00%)
    6 / 62 (9.68%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    20
    0
    0
    0
    Infusion site oedema
         subjects affected / exposed
    1 / 70 (1.43%)
    4 / 62 (6.45%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    24
    0
    0
    0
    Infusion site pain
         subjects affected / exposed
    2 / 70 (2.86%)
    5 / 62 (8.06%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    8
    11
    0
    0
    0
    Infusion site pruritus
         subjects affected / exposed
    0 / 70 (0.00%)
    4 / 62 (6.45%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    6
    0
    0
    0
    Injection site erythema
         subjects affected / exposed
    0 / 70 (0.00%)
    7 / 62 (11.29%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    16
    0
    0
    0
    Injection site pain
         subjects affected / exposed
    2 / 70 (2.86%)
    5 / 62 (8.06%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    4
    19
    0
    0
    0
    Injection site pruritus
         subjects affected / exposed
    0 / 70 (0.00%)
    4 / 62 (6.45%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    9
    0
    0
    0
    Pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    6
    0
    Pyrexia
         subjects affected / exposed
    1 / 70 (1.43%)
    7 / 62 (11.29%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    1 / 16 (6.25%)
         occurrences all number
    1
    9
    0
    2
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 70 (2.86%)
    7 / 62 (11.29%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    2
    8
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    5 / 70 (7.14%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    7
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Vomiting
         subjects affected / exposed
    4 / 70 (5.71%)
    1 / 62 (1.61%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 16 (0.00%)
         occurrences all number
    4
    1
    0
    1
    0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 62 (0.00%)
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Nasal dryness
         subjects affected / exposed
    0 / 70 (0.00%)
    0 / 62 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 70 (1.43%)
    5 / 62 (8.06%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    14
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 70 (1.43%)
    3 / 62 (4.84%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    10
    0
    1
    0
    Back pain
         subjects affected / exposed
    2 / 70 (2.86%)
    4 / 62 (6.45%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    3
    4
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 62 (1.61%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    3
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Aug 2015
    Amendment 1 • The Schedule of Study Procedures and Assessments, Clinical Laboratory Assessments were updated to include assessments that were missed in the original protocol. • Added the text “the Declaration of Helsinki (October 2013)” to the compliance statement. • The text related to unblinding was updated to clarify that the responsibility to break the treatment code in emergency situations resided solely with the investigator. • The safety reporting section was updated to clarify that it was the sponsor’s responsibility to inform the relevant regulatory authorities, ethics committees, and investigators worldwide of any suspected unexpected serious adverse reactions (SUSARs) and all other SAEs in a timely manner in accordance with applicable regulations, such as the European Clinical Trial Directive (2001/20/EC).
    22 Apr 2016
    Amendment 2 • A secondary outcome measure was added to Epoch 1 and Epoch 2, and additional tertiary outcome measures were added to Epoch 2 to gain additional relevant information regarding outcome measures of efficacy. • The circumstances under which LDH isoenzyme testing would occur were clarified throughout the document. • In response to specific regulatory agency feedback, an additional inclusion criterion was added to ensure that participants were willing and able to sign an ICF. • Screening and Baseline Period was updated to clarify the use of previous EDX records during screening. • End of IV Treatment Period was updated to clarify that only participants who completed Epoch 1 may opt to participate in the open-label extension (Epoch 2). • Hand Grip Strength was updated as the instrument used to measure hand grip strength was changed from the JAMAR® PLUS + Hand Dynamometer to the Vigorimeter. • A new section was added to the protocol to clarify the ethical considerations of the trial. • Inclusion Criteria was updated by recommendation of the Canadian investigator to include males or females of age ≥18 at the time of screening. • Throughout the protocol, the minimal monthly maintenance dose of IGIV was decreased from 0.5 to 0.4 g/kg after discussion with the EU, US, and Canadian investigators and key opinion leaders. • Exclusion Criteria, Rescreening, and Section 10.5 Mediations and Non-drug Therapies were updated to allow for steroid treatment if administered >3 months prior to screening and within 3 months of screening allowing for a single steroid dose or Methylprednisolone Dose Pack for the treatment of AE and non-CIDP indications.
    22 Apr 2016
    Amendment 2 continued: • Overall Study Design and Schedule of Study Procedures and Assessments were updated to include unscheduled visits in Epoch 2 at any time during the treatment period. • The safety sections of the protocol (Serious Adverse Event Reporting, Safety Reporting, Untoward Medical Occurrences) were updated to include the reporting of all SAEs, including SUSARs, on the Serious Adverse Event Report Form and transmitted to the Sponsor within 24 hours after becoming aware of an event. Updated from eCRF reporting to SAE Report Form reporting. • Preparation and Storage of Pooled Products was updated to allow unblinded staff (nurse) to prepare the study drug, and ensure the infusions were stored and administered at the correct temperature. • Data Monitoring Committee was updated to state that the DMC may recommend to stop the trial if it finds toxicities or if the treatment was proven to be beneficial. • Inclusion Criteria (inclusion criterion 3) was updated to clarify the reasons participants may have received IgG treatment. • Withdrawal and Discontinuation was updated with language to specify that the participation in the Pregnancy Registry is based on whether it is available in the respective country. • Definitions was updated to include the definition of a TEAE. • Suspected and Unexpected Serious Adverse Reactions was added into the protocol. • Backup Samples/Biobanking was updated to include the clause “for no more than 2 years after the final study report has been completed” for the storage of serum samples. • Synopsis, Administration, Description of Treatment were updated to divide the mode of administration into 2 parts, 1 for bifurcated needle set, and 1 for trifurcated needle set.
    30 Jan 2018
    Amendment 3 • Overall Study Design, Schedule of Study Procedures and Assessments (Table 21-1, Table 21-2, Table 21-3), a reference point was added for Week 1 to ensure consistency from all sites on determining Week 1. • Duration of Study Periods and Participant Participation were updated to include new estimates of study completion and duration in line with the extended enrolment period. Inclusion Criteria was updated to remove the time limit on INCAT scores and replaced with documentation in medical records. • Inclusion Criteria, and Section 21.3 Schedule of Study Procedures and Assessments (Table 21-1, Table 21-2, Table 21-3) were updated to include the definition of stability in the inclusion criteria. • Inclusion Criteria was updated to include detail of INCAT scoring in inclusion criterion 4. • Exclusion Criteria was updated to include “MADSAM” in the list of hereditary demyelinating neuropathies for clarity for the investigators. • Background Information was updated to include a new reference to the sentence summarizing current publications on CIDP. • rHuPH20 was updated to include additional half-life information for rHuPH20. • Placebo control was updated to include the possible names of the placebo control in various countries. • Clinical Condition/Indication was updated to include ‘Relapse of’ in the clinical condition of Epoch 1 to align with the synopsis. • Population to be Studied, Brief Summary, Section 9.1 Inclusion Criteria, Screening and Baseline Period, and Rescreening were updated to clarify the description of the stable dosing regimen of IGIV therapy from 3 months to 12 weeks. • GGL/KIOVIG was updated to change the term “pharyngolaryngeal pain” to “laryngeal pain” in line with the current MedDRA PT
    30 Jan 2018
    Amendment 3 continued: Compliance Statement was updated to remove ‘The Declaration of Helsinki (October 2013)’ to align with the newest template language. • Screening and Baseline Period was updated to increase the dosing interval from 5 to 7 days. The section was also updated to include ‘product name’ as in the list of information captured for prerandomization IGIV infusion. • SC Infusion Visits, IV Infusion Visits were updated to clarify the window around the telephone follow-up visits. • Participant Diary and PROs was updated to clarify that the diary was the source records for patient reported data. The section was also updated to remove the text ‘After reconciliation against eCRF, the data will be imported into the study database’. The study database would not be reconciled against the diary, the information would be reviewed by the investigator. • Participant Completion/Discontinuation was updated to include death as a reason for discontinuation. • R-ODS was updated to include additional information on eDiaries at screening. • SUSAR was updated to include text required by the Voluntary Harmonization Procedure. • Assessment of AEs was updated to include the qualifier of 30 days for SAE reported after study completion using the SAE Report Form. Additional text was added regarding the use of Council for International Organizations of Medical Sciences (CIOMS) forms or MedWatch forms after the 30 days from study completion. • Hematology and Clinical Chemistry, Table 21-1, Table 21-2, Table 21-3, Table 21-4, Table 21-5, Table 21-6, Table 21-7, and Table 21-8 were updated to include a window for Hgb and hematocrit, and specifications for when a reticulocyte count would be performed was added to the body text, removed from tables (21-1, 21-2, 21-3, 21-4, 21-5, 21-6, and 21-7) and added to Table 21-8.
    30 Jan 2018
    Amendment 3 continued: • Assessment of Abnormal Laboratory Values was updated to include specifications that investigators did not need to indicate if hyaluronidase antibody values constituted an AE. • Trough Serum IgG was updated to remove ‘within 60 minutes’ from the sentence regarding when the IgG sample must be collected. • Guidance on Reporting and Assessing rHuPH20 (hyaluronidase) antibody test results was updated to include guidance on reporting and assessing antibody results. • Updated to remove the following clause ‘participant’s electronic diary (as applicable)’. • Planned Interim Safety Analysis of the Study were updated to include details of a formal interim analysis for submission purposes. • Safety were updated to include a note to safety outcome measures: ‘Note: Adverse events in this section refer to treatment-emergent AEs, if not specified’. • Blinding was updated that specifications that Epoch 1 was blinded and Epoch 2 was open-label were added, a definition of completion was also added for Epoch 1 participants. • Unblinding language was updated from the standard unblinding language to describe that treatment assignments were unblinded after Epoch 1. • Placebo Solution was updated to include additional text describing the placebo packaging, including coloration and dilution. • Epoch 2 was updated to specify maintenance infusions for GGL/KIOVIG and GAMUNEX-C. A maximum dose was also added. The clause ‘every 3 weeks’ was added to the mode of administration section for GGL/KIOVIG to emphasize that this was a fixed dose schedule. • Datasets and Analysis Cohorts, the definition of a PP analysis set was updated for consistency within the company and between the final and interim analyses.
    30 Jan 2018
    Amendment 3 continued: • In the Synopsis, the timing for subsequent doses for GAMMAGARD was updated from 1 to 2 days to 2 to 5 days. • Laboratory and Reader Standardization was updated to remove R-ODS from the list as it was not a participant reported outcome. • Schematics for Study Visits and Assessments Figure 21-1, Figure 21-2 were removed. References to these figures were removed throughout the protocol. •Schedule of Study Procedures and Assessments was updated. • Clinical Laboratory Assessments (Table 21-5, Table 21-6, Table 21-7, Table 21-8), a clause was added indicating that participants who met the criteria would have to return for additional testing. • Clinical Laboratory Assessments Table 21-5 was updated to add a footnote to the serum IgG to align with the protocol body text.
    12 Feb 2019
    Amendment 4 •The overall duration of the study was extended to 68 months and the enrollment period was extended to 61 months. • A reference to GAMUNEX-C prescribing instruction (for storage conditions) was included in the synopsis. • The mode of administration of GAMUNEX-C was amended. • Inclusion criteria, inclusion criterion 5 was corrected to include a cross-reference • Exclusion criteria were updated to improve the instructions to the investigators for clearer directions on participant eligibility and include an exclusion criterion for thrombophilic disorders. • Unblinding was updated to include unblinding language from protocol amendment 2 (dated 22 Apr 2016) and provide additional information • Placebo solution was updated to include the storage temperature of LR solution. • Epoch 1 was updated to include “for both rHuPH20 and IGI,10%/placebo solution” to improve clarity in the protocol. • HYQVIA/HyQvia, Section 9.3 Withdrawal and Discontinuation, SAEs, Assessment of AEs were updated as enrolment in the Pregnancy Registry had been closed. • Hematology and Clinical Chemistry was updated to clarify the description of sampling time points as per the US FDA’s recommendation. • Hemolytic Panel was updated to improve clarity/readability and reflect the same instructions previously provided to sites in memos. • Schedule of Assessments was updated to improve assessments and clarity of the protocol, and to change the frequency of the assessment of the INCAT disability score in response to regulatory requirements.
    10 May 2019
    Amendment 5 • Exclusion Criteria, Screening and Baseline Period, and Medications and Non-drug Therapies were updated preclude use of any corticosteroids within 8 weeks prior to screening, regardless of indication. • Methods of Analysis, and Trough Serum IgG were updated to include the following outcome measure: In addition, potential correlation between serum IgG trough levels on or after Day 120 or at the time of CIDP symptom relapse and relapse status (relapse, no relapse) will be assessed as an exploratory analysis. • Compliance Statement was updated to clarify the study would be conducted in accordance with EU Directives (2001/20/EC; 2005/28/EC). • Source Data was updated to clarify that all data entered in to the CRF should be able to be verified by a corresponding source document. • INCAT disability Scale and MRC sum score were updated to clarify that the same individual should administer the hand grip Strength, INCAT and MRC tests. • were updated at the request of the US FDA to include that infusion site swelling following SC infusion would be captured and reported as AEs. • Safety was updated at the request of the US FDA to include that the incidence of local infusion site reactions would be reported by geographic region (US, non-US) and overall. • Schedule of Study Procedures and Assessments was updated to remove the collection of BMI at several visits. • Schedule of Study Procedures and Assessments and Clinical Laboratory Assessments were updated to correct footnotes as per protocol amendment 4.
    20 May 2021
    Amendment 6 • Duration of Study Periods and Participant Participation were updated; the maximum overall duration of the study was changed from 68 to 72 months, and the enrollment period was changed from 61 to 64 months. • Tertiary Objectives, and Other Assessments were updated to include additional tertiary objective for Epoch 1 to better assess treatment benefit in participants. • Tertiary Objectives was updated to include an additional tertiary objective for Epoch 2 to better assess treatment effects. • Study Stopping Rules, Sample Size and Power Calculations, and Power Calculation were updated to include further detail related to stopping randomization in Epoch 1. • Synopsis was updated to add the requirement to collect trough serum IgG levels and PRO measures. • Study Design were updated with details related to administration of IP at the sire, infusion related data to be recorded and participant/caregiver’s training. • Efficacy were updated to add tertiary outcome measures for Epoch 1. • Efficacy were updated to add tertiary outcome measured for Epoch 2.
    20 May 2021
    Amendment 6 continued: • Study Design, Administration, and Epoch 2, details related to the mode of administration and specifications of infusion pump were revised due to the pump recall in the US of the body guard. • Tertiary Outcome Measures were updated to include details related to statistical analysis of R-ODS score and DAs based on EDX studies (tertiary outcome measures). • Synopsis was updated to remove a footnote relating to the pump occlusion alarm. • Background Information was updated to include literature references describing therapeutic efficacy and safety of IGSC treatment and impact of COVID-19 pandemic on ongoing drug development efforts. • Unblinding was updated to reflect updated study procedures. • Study Stopping Rules and Section 8.6.1 Operational Procedures for Study Stopping were updated to reflect updated study stopping rules. • Trial Integrity was added. • Alternative Approaches to Study Procedures and Data collection due to COVID-19 Related Factors was added to reflect changes made in response to the COVID-19 pandemic. • R-ODS was updated to introduce patient-centric endpoint. • EDX Studies (electromyography) was added to describe EDX studies. • Handling of Missing, Unused, and Spurious Data was updated to clarify rules for handling missing data would be described in the SAP. • Primary Outcome Measure were updated to include a sensitivity analysis with an alternative relapse definition.

    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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