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    Clinical Trial Results:
    A Randomized, Open-Label, Multi-Centre, Active Control Study Investigating the Efficacy and Safety of Imlifidase in Eliminating Donor Specific Anti-HLA Antibodies in the Treatment of Active Antibody-Mediated Rejection in Kidney Transplant Patients

    Summary
    EudraCT number
    		 2018-000022-66
    Trial protocol
    		 FR   AT   DE  
    Global end of trial date
    16 Nov 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Feb 2024
    First version publication date
    17 Feb 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    16-HMedIdeS-12
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03897205
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Hansa Biopharma AB
    Sponsor organisation address
    Scheelevägen 22, Lund, Sweden, 223 63
    Public contact
    Clinical contact information, Hansa Biopharma AB, +46 046165670, clinicalstudyinfo@hansabiopharma.com
    Scientific contact
    Clinical contact information, Hansa Biopharma AB, +46 046165670, clinicalstudyinfo@hansabiopharma.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
    09 Oct 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 May 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Nov 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Investigate the efficacy of imlifidase compared with plasma exchange (PE) in removal of donor specific antibodies (DSA) in patients who are experiencing an active or chronic active AMR episode after kidney transplantation
    Protection of trial subjects
    Details of the goals of the research and the risk and benefits of the protocol were reviewed with each potential study subject. In the event of adverse events from the study, full resources of the hospital were available to intervene as medically necessary. Physicians expert in the care of patients with AMR were responsible for the patients' care at each site. To mitigate the risk of infections all patients received a standard regimen of antibiotics according to local clinical practice, starting before the first treatment and continuing until IgG levels had returned to acceptable values, as judged by the investigator. All patients in the imlifidase arm received antihistamine before administration of imlifidase and all patients in both treatment arms were treated in accordance with the study protocol with the background therapy described below.
    Background therapy
    		 All patients received pulse methylprednisolone Day 1 to Day 3, followed by a tapering schedule with prednisolone/prednisone. Patients randomised to imlifidase received their first dose of methylprednisolone before imlifidase was administered. The patients did also receive high dose intravenous immunoglobulin (IVIg) 3 days after imlifidase treatment or directly after the last PE. In addition a single dose of rituximab was given 5 days after completed IVIg infusion.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Aug 2019
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 3 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 4
    Country: Number of subjects enrolled
    France: 13
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    United States: 3
    Country: Number of subjects enrolled
    Australia: 1
    Worldwide total number of subjects
    29
    EEA total number of subjects
    25
    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)
    25
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Patients were recruited between 06-AUG-2019 and 20-MAY-2022.

    Pre-assignment
    Screening details
    		 A total of 34 patients were screened, 30 were randomised, and 29 were included in the study.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Blinding was not feasible due to the nature of the standard of care treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Imlifidase
    Arm description
    		 Patients treated with imlifidase
    Arm type
    		 Experimental

    Investigational medicinal product name
    Imlifidase
    Investigational medicinal product code
    Other name
    IdeS, IgG endopeptidase
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    One intravenous dose of imlifidase, 0.25 mg/kg, administered over 15 minutes.

    Arm title
    		 Plasma exchange (PE)
    Arm description
    		 Patients treated with SOC, i.e. PE
    Arm type
    		 Medical procedure-Active comparato

    Investigational medicinal product name
    Plasma exchange
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Pharmaceutical dose form not applicable
    Routes of administration
    Route of administration not applicable
    Dosage and administration details
    Plasma exchange is a medicinal procedure

    Number of subjects in period 1
    		Imlifidase Plasma exchange (PE)
    Started
    19
    10
    Completed
    17
    10
    Not completed
    2
    0
         Adverse event, serious fatal
    1
    -
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Imlifidase
    Reporting group description
    		 Patients treated with imlifidase

    Reporting group title
    Plasma exchange (PE)
    Reporting group description
    		 Patients treated with SOC, i.e. PE

    Reporting group values
    		 Imlifidase Plasma exchange (PE) Total
    Number of subjects
    		 19 10 29
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 17 8 25
        From 65-84 years
    		 2 2 4
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 43.7 ( 13.7 ) 52.8 ( 16.4 ) -
    Gender categorical
    Units: Subjects
        Female
    		 8 5 13
        Male
    		 11 5 16

    End points

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    End points reporting groups
    Reporting group title
    Imlifidase
    Reporting group description
    		 Patients treated with imlifidase

    Reporting group title
    Plasma exchange (PE)
    Reporting group description
    		 Patients treated with SOC, i.e. PE

    Subject analysis set title
    PK analysis set
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    PK analysis set includes patients receiving any amount of imlifidase.

    Primary: Maximum Reduction in Donor Specific Antibodies (DSA) Level During the 5 Days Following the Start of Treatment

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    End point title
    		 Maximum Reduction in Donor Specific Antibodies (DSA) Level During the 5 Days Following the Start of Treatment [1]
    End point description
    Maximum reduction (%) in the sum of DSA at any time point during the 5 days following the start of treatment. Only DSA with ≥1000 mean fluorescence intensity (MFI) at pre-treatment were included in the calculations.
    End point type
    Primary
    End point timeframe
    Start of treatment until 5 days following start of treatment
    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: Due to the exploratory nature of this trial, no formal hypothesis was tested.
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    18 [2]
    8 [3]
    Units: Maximum reduction (%)
        arithmetic mean (standard deviation)
    94 ( 4 )
    36 ( 26 )
    Notes
    [2] - 1 patient excluded did not have MFIs above 1000
    [3] - 2 patients excluded did not have MFI above 1000
    No statistical analyses for this end point

    Secondary: Reduction in DSA Levels After Treatment

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    End point title
    		 Reduction in DSA Levels After Treatment
    End point description
    DSA levels were assessed at all visits throughout the study. The results are presented as reduction (%) from baseline. A negative value represents an increase from baseline.
    End point type
    Secondary
    End point timeframe
    Screening until Day 180
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    18
    8
    Units: Reduction from baseline (%)
    arithmetic mean (standard deviation)
        2 hours
    91 ( 7 )
    -2 ( 28 )
        6 hours
    94 ( 4 )
    -2 ( 33 )
        24 hours
    92 ( 5 )
    0 ( 25 )
        48 hours
    89 ( 10 )
    18 ( 34 )
        72 hours
    83 ( 24 )
    10 ( 32 )
        96 hours
    58 ( 32 )
    22 ( 26 )
        Day 6
    41 ( 42 )
    31 ( 23 )
        Day 8
    33 ( 45 )
    39 ( 20 )
        Day 11
    35 ( 34 )
    22 ( 34 )
        Day 15
    31 ( 43 )
    28 ( 36 )
        Day 22
    28 ( 46 )
    23 ( 34 )
        Day 29
    35 ( 30 )
    30 ( 14 )
        Day 64
    30 ( 38 )
    32 ( 34 )
        Day 90
    25 ( 41 )
    41 ( 33 )
        Day 180
    29 ( 38 )
    35 ( 32 )
    No statistical analyses for this end point

    Secondary: Estimated Glomerular Filtration Rate (eGFR) Levels

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    End point title
    		 Estimated Glomerular Filtration Rate (eGFR) Levels
    End point description
    eGFR as calculated from p-creatinine is a measure of kidney function. eGFR was assessed at all visits throughout the study.
    End point type
    Secondary
    End point timeframe
    Screening until Day 180
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19 [4]
    10
    Units: mL/min/1.73m2
    arithmetic mean (standard deviation)
        Pre-dose
    28.0 ( 14.0 )
    21.0 ( 8.1 )
        24 hours
    25.8 ( 13.8 )
    23.5 ( 11.0 )
        48 hours
    26.2 ( 14.5 )
    25.7 ( 9.4 )
        72 hours
    27.6 ( 15.9 )
    27.2 ( 10.8 )
        96 hours
    30.6 ( 19.5 )
    30.5 ( 13.8 )
        Day 6
    30.3 ( 18.6 )
    31.2 ( 12.9 )
        Day 8
    33.4 ( 21.1 )
    36.2 ( 18.2 )
        Day 11
    32.2 ( 18.9 )
    34.0 ( 16.6 )
        Day 15
    32.1 ( 19.3 )
    31.1 ( 15.4 )
        Day 22
    29.8 ( 16.7 )
    31.9 ( 14.8 )
        Day 29
    27.5 ( 15.3 )
    31.7 ( 14.5 )
        Day 64
    29.4 ( 14.9 )
    34.6 ( 14.5 )
        Day 90
    27.2 ( 16.7 )
    31.6 ( 12.8 )
        Day 180
    29.9 ( 15.5 )
    32.5 ( 17.8 )
    Notes
    [4] - Some patients had missing values at sporadic occasions throughout the trial
    No statistical analyses for this end point

    Secondary: Urine albumin/creatinine

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    End point title
    		 Urine albumin/creatinine
    End point description
    The albumin/creatinine ratio in urine is a measure of kidney function.
    End point type
    Secondary
    End point timeframe
    Pre-dose until Day 180
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19 [5]
    10 [6]
    Units: Ratio
    arithmetic mean (standard deviation)
        Pre-dose
    626 ( 972 )
    134 ( 165 )
        Day 90
    669 ( 964 )
    119 ( 166 )
        Day 180
    815 ( 1018 )
    242 ( 295 )
    Notes
    [5] - Some patients had missing values at different occasions during the study.
    [6] - Some patients had missing values at different occasions during the study.
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Graft Loss Within 180 Days of Treatment

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    End point title
    		 Proportion of Patients With Graft Loss Within 180 Days of Treatment
    End point description
    Information on patients who experienced graft loss was collected throughout the study.
    End point type
    Secondary
    End point timeframe
    Screening until Day 180
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19
    10
    Units: Number of patients
        number (not applicable)
    5
    0
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Signs or no Signs of Transplant Glomerulopathy at Day 180

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    End point title
    		 Proportion of Patients With Signs or no Signs of Transplant Glomerulopathy at Day 180
    End point description
    Biopsies collected 180 days after treatment were analysed for signs of glomerulopathy.
    End point type
    Secondary
    End point timeframe
    Day 180
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19
    10
    Units: Number of patients
    number (not applicable)
        No signs of transplant glomerulopathy
    7
    4
        Signs of transplant glomerulopathy
    8
    6
        No biopsy result or no evaluable biopsy result
    4
    0
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Resolved AMR as Assessed by Messenger Ribonucleic Acid (mRNA) Levels

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    End point title
    		 Proportion of Patients With Resolved AMR as Assessed by Messenger Ribonucleic Acid (mRNA) Levels
    End point description
    Kidney biopsies were taken at screening, Day 29, and Day 180. Changes from baseline in mRNA levels were assessed as evidence of resolved AMR.
    End point type
    Secondary
    End point timeframe
    Screening, Day 29, and Day 180
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19
    10
    Units: Number of patients
    number (not applicable)
        Day 29
    0
    0
        Day 180
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Administered Plasma Exchange (PE) and Immunoadsorption (IA) Sessions

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    End point title
    		 Number of Administered Plasma Exchange (PE) and Immunoadsorption (IA) Sessions
    End point description
    Total number of administered PE and IA sessions to each treatment group are presented during the complete trial (Day 1 to Day 180) and for the time period: start of IVIg administration to Day 180.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19
    10
    Units: Number of sessions
    number (not applicable)
        Number of PE from Day 1 to Day 180
    20
    70
        Number of PE administered after start of IVIg
    18
    11
        Number of IA from Day 1 to Day 180
    0
    23
        Number of IA administered after start of IVIg
    0
    23
    No statistical analyses for this end point

    Secondary: Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg)

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    End point title
    		 Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg)
    End point description
    Total serum IgG levels over time following treatment until administration of IVIg. Please observe, IVIg was initiated on Day 4 (before 96 h measurement) for the imlifidase group.
    End point type
    Secondary
    End point timeframe
    Pre-dose until Day 6
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19
    10
    Units: mg/mL
    arithmetic mean (standard deviation)
        Pre-dose
    8.6 ( 6.1 )
    7.9 ( 5.5 )
        2 hours
    0.2 ( 0.1 )
    4.3 ( 3.5 )
        6 hours
    0.2 ( 0.1 )
    4.6 ( 3.6 )
        24 hours
    0.2 ( 0.2 )
    5.2 ( 3.7 )
        48 hours
    0.2 ( 0.2 )
    4.6 ( 4.3 )
        72 hours
    0.5 ( 0.8 )
    4.8 ( 4.3 )
        96 hours
    11.7 ( 5.4 )
    4.1 ( 4.3 )
        Day 6
    20.0 ( 8.4 )
    4.2 ( 4.5 )
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Intact IgG Following Treatment Until Administration of IVIg

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    End point title
    		 Proportion of Patients With Intact IgG Following Treatment Until Administration of IVIg
    End point description
    Presence of IgG, scIgG, and F(ab')2 was analysed using sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE)/western blot. Of note, IVIg was administered on Day 4 (before 96 h measurement) to patients treated with imlifidase. Hence no analyses beyond this timepoint were performed for this group.
    End point type
    Secondary
    End point timeframe
    Start of treatment (Day 1) up to administration of IVIg on Day 4 (imlifidase group) and until administration of IVIg within Day 15 (PE group)
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19 [7]
    10 [8]
    Units: Number of patients
    number (not applicable)
        Baseline
    19
    10
        2 hours
    0
    10
        6 hours
    0
    10
        24 hours
    0
    9
        48 hours
    0
    8
        72 hours
    0
    10
        96 hours
    0
    9
        Day 6
    0
    10
        Day 8
    0
    8
        Day 11
    0
    5
        Day 15
    0
    1
    Notes
    [7] - 19 patients analysed up to 72 hours then 0 patients at all following timepoints
    [8] - 10 patients analysed up to Day 6, then 8 at Day 8, 5 at Day 11, and 2 at Day 15
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Mixed Intact IgG and scIgG Following Treatment Until Administration of IVIg

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    End point title
    		 Proportion of Patients With Mixed Intact IgG and scIgG Following Treatment Until Administration of IVIg
    End point description
    Presence of IgG, scIgG, and F(ab')2 was analysed using sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE)/western blot. Of note, IVIg was administered on Day 4 (before 96 h measurement) to patients treated with imlifidase. Hence no analyses beyond this timepoint were performed for this group.
    End point type
    Secondary
    End point timeframe
    Start of treatment (Day 1) up to administration of IVIg on Day 4 (imlifidase group) and until administration of IVIg within Day 15 (PE group)
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19 [9]
    10 [10]
    Units: Number of patients
    number (not applicable)
        Baseline
    0
    0
        2 hours
    0
    0
        6 hours
    0
    0
        24 hours
    0
    0
        48 hours
    0
    0
        72 hours
    2
    0
        96 hours
    0
    0
        Day 6
    0
    0
        Day 8
    0
    0
        Day 11
    0
    0
        Day 15
    0
    0
    Notes
    [9] - 19 patients analysed up to 72 hours and 0 patients at all following timepoints.
    [10] - 10 patients up to Day 6, 8 at Day 8, 5 at Day 11, and 2 at Day 15
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Only scIgG Following Treatment Until Administration of IVIg

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    End point title
    		 Proportion of Patients With Only scIgG Following Treatment Until Administration of IVIg
    End point description
    Presence of IgG, scIgG, and F(ab')2 was analysed using sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE)/western blot. Of note, IVIg was administered on Day 4 (before 96 h measurement) to patients treated with imlifidase. Hence no analyses beyond this timepoint were performed for this group.
    End point type
    Secondary
    End point timeframe
    Start of treatment (Day 1) up to administration of IVIg on Day 4 (imlifidase group) and until administration of IVIg within Day 15 (PE group)
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19 [11]
    10 [12]
    Units: Number of patients
    number (not applicable)
        Baseline
    0
    0
        2 hours
    0
    0
        6 hours
    0
    0
        24 hours
    0
    0
        48 hours
    0
    0
        72 hours
    0
    0
        96 hours
    0
    0
        Day 6
    0
    0
        Day 8
    0
    0
        Day 11
    0
    0
        Day 15
    0
    0
    Notes
    [11] - 19 patient were analysed up to 72 hours thereafter 0 patients at all following timepoints
    [12] - 10 patients up to Day 6, 8 at Day 8, 5 at Day 11 and 2 at Day 15
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Mixed scIgG and F(ab')2 Fragments Following Treatment Until Administration of IVIg

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    End point title
    		 Proportion of Patients With Mixed scIgG and F(ab')2 Fragments Following Treatment Until Administration of IVIg
    End point description
    Presence of IgG, scIgG, and F(ab')2 was analysed using sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE)/western blot. Of note, IVIg was administered on Day 4 (before 96 h measurement) to patients treated with imlifidase. Hence no analyses beyond this timepoint were performed for this group.
    End point type
    Secondary
    End point timeframe
    Start of treatment (Day 1) up to administration of IVIg on Day 4 (imlifidase group) and until administration of IVIg within Day 15 (PE group)
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19 [13]
    10 [14]
    Units: Number of patients
    number (not applicable)
        Baseline
    0
    0
        2 hours
    2
    0
        6 hours
    0
    0
        24 hours
    0
    0
        48 hours
    1
    0
        72 hours
    1
    0
        96 hours
    0
    0
        Day 6
    0
    0
        Day 8
    0
    0
        Day 11
    0
    0
        Day 15
    0
    0
    Notes
    [13] - 19 patients analysed up to 72 hours thereafter 0 patients at all following timepoints
    [14] - 10 patients analysed up to Day 6, 8 at Day 8, 5 at Day 11, and 2 at Day 15
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Only F(ab')2 Fragments Following Treatment Until Administration of IVIg

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    End point title
    		 Proportion of Patients With Only F(ab')2 Fragments Following Treatment Until Administration of IVIg
    End point description
    Presence of IgG, scIgG, and F(ab')2 was analysed using sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE)/western blot. Of note, IVIg was administered on Day 4 (before 96 h measurement) to patients treated with imlifidase. Hence no analyses beyond this timepoint were performed for this group.
    End point type
    Secondary
    End point timeframe
    Start of treatment (Day 1) up to administration of IVIg on Day 4 (imlifidase group) and until administration of IVIg within Day 15 (PE group)
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19 [15]
    10 [16]
    Units: Number of patients
    number (not applicable)
        Baseline
    0
    0
        2 hours
    17
    0
        6 hours
    19
    0
        24 hours
    19
    0
        48 hours
    18
    0
        72 hours
    16
    0
        96 hours
    0
    0
        Day 6
    0
    0
        Day 8
    0
    0
        Day 11
    0
    0
        Day 15
    0
    0
    Notes
    [15] - 19 patients analysed up to 72 hours and thereafter 0 at all following timepoints
    [16] - 10 patients analysed up to Day 6, 8 at Day 8, 5 at Day 11, and 2 at Day 15
    No statistical analyses for this end point

    Secondary: Proportion of Patients With No Intact IgG, scIgG, or F(ab')2 Fragments Following Treatment Until Administration of IVIg

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    End point title
    		 Proportion of Patients With No Intact IgG, scIgG, or F(ab')2 Fragments Following Treatment Until Administration of IVIg
    End point description
    Presence of IgG, scIgG, and F(ab')2 was analysed using sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE)/western blot. Of note, IVIg was administered on Day 4 (before 96 h measurement) to patients treated with imlifidase. Hence no analyses beyond this timepoint were performed for this group.
    End point type
    Secondary
    End point timeframe
    Start of treatment (Day 1) up to administration of IVIg on Day 4 (imlifidase group) and until administration of IVIg within Day 15 (PE group)
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19 [17]
    10 [18]
    Units: Number of patients
    number (not applicable)
        Baseline
    0
    0
        2 hours
    0
    0
        6 hours
    0
    0
        24 hours
    0
    1
        48 hours
    0
    2
        72 hours
    0
    0
        96 hours
    0
    1
        Day 6
    0
    0
        Day 8
    0
    0
        Day 11
    0
    0
        Day 15
    0
    1
    Notes
    [17] - 19 patients were analysed up to 72 hours thereafter 0 patients at all following timepoints
    [18] - 10 patients were analysed up to Day 6, 8 at Day 8, 5 at Day 11, and 2 at Day 15
    No statistical analyses for this end point

    Secondary: DSA Functionality Determined by C1q Analysis Pre- and Post-treatment

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    End point title
    		 DSA Functionality Determined by C1q Analysis Pre- and Post-treatment
    End point description
    An MFI value above 6000 is indicative of complement fixation. Analysis of DSA functionality assessed as mean MFI levels was done before and after treatment.
    End point type
    Secondary
    End point timeframe
    Screening until Day 6
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19 [19]
    10 [20]
    Units: MFI counts
    arithmetic mean (standard deviation)
        Pre-dose
    19827 ( 11910 )
    18848 ( 9958 )
        Day 2
    319 ( 432 )
    15576 ( 12008 )
        Day 6
    5065 ( 9768 )
    11926 ( 13076 )
    Notes
    [19] - 11 patients were evaluable pre-dose, Day 2 and 10 patients Day 6
    [20] - 6 patients were evaluable pre-dose, Day 2, and Day 6
    No statistical analyses for this end point

    Secondary: Pharmacokinetics of Imlifidase

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    End point title
    		 Pharmacokinetics of Imlifidase
    End point description
    Cmax = Maximum observed plasma concentration of imlifidase following dosing Tmax = Time point for maximum observed plasma concentration of imlifidase following dosing t1/2 = Terminal half-life of imlifidase (alpha t1/2 corresponds to the initial phase and beta t1/2 corresponds to the elimination phase) AUC = Area under the imlifidase plasma concentration vs time curve CL = Clearance of imlifidase means the volume of blood cleared of imlifidase per unit of time Vss = Volume of distribution associated with steady state VZ = Volume of distribution associated with the elimination phase
    End point type
    Secondary
    End point timeframe
    Start of treatment until Day 15
    End point values
    		 PK analysis set
    Number of subjects analysed
    19 [21]
    Units: Result
    median (full range (min-max))
        Cmax (μg/mL)
    4.2 (2.8 to 5.7)
        Tmax (h)
    0.6 (0.4 to 2.3)
        alpha-t1/2 (h)
    2.7 (1.4 to 6.0)
        beta-t1/2 (h)
    39.7 (23.5 to 128.0)
        AUC (h×μg/mL)
    127.0 (37.2 to 325.5)
        CL (mL/h/kg)
    1.87 (0.77 to 6.72)
        Vss (L/kg)
    0.20 (0.10 to 9.85)
        Vz (L/kg)
    0.18 (0.11 to 8.41)
    Notes
    [21] - 16 patients were evaluable for AUC, beta-t1/2, CL, Vss, and Vz and 13 for alpha-t1/2
    No statistical analyses for this end point

    Secondary: Concentration of Anti-drug Antibodies (ADAs)

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    End point title
    		 Concentration of Anti-drug Antibodies (ADAs)
    End point description
    Samples were collected and analysed for presence of anti-imlifidase IgG throughout the study. Imlifidase is an IgG-degrading enzyme of Streptococcus pyogenes. Patients who have been exposed to Streptococcus prior to participating in this trial tested positive for ADA also before exposure to imlifidase.
    End point type
    Secondary
    End point timeframe
    Screening until Day 180
    End point values
    		 PK analysis set
    Number of subjects analysed
    19
    Units: mg/L
    geometric mean (geometric coefficient of variation)
        Pre-dose
    6.7 ( 70 )
        24 hours
    2.0 ( 0 )
        Day 8
    15 ( 66 )
        Day 11
    20 ( 149 )
        Day 15
    49 ( 275 )
        Day 22
    73 ( 300 )
        Day 29
    87 ( 398 )
        Day 64
    122 ( 496 )
        Day 90
    135 ( 536 )
        Day 180
    100 ( 725 )
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Different Types of Kidney Histopathology at Screening

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    End point title
    		 Proportion of Patients With Different Types of Kidney Histopathology at Screening
    End point description
    Kidney biopsies were assessed according to the Banff (2017 or 2019) criteria at screening (baseline), Day 29, and Day 180.
    End point type
    Secondary
    End point timeframe
    Screening
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19
    10
    Units: Patients
    number (not applicable)
        Active AMR
    7
    4
        Active AMR + Borderline CMR
    0
    1
        Active AMR + CMR
    5
    1
        Chronic Active AMR + Borderline CMR
    3
    1
        Chronic Active AMR + CMR
    1
    2
        Chronic Active AMR
    3
    1
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Different Types of Kidney Histopathology at Day 29

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    End point title
    		 Proportion of Patients With Different Types of Kidney Histopathology at Day 29
    End point description
    Kidney biopsies were assessed according to the Banff (2017 or 2019) criteria at screening (baseline), Day 29, and Day 180.
    End point type
    Secondary
    End point timeframe
    Day 29
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19
    10
    Units: Patients
    number (not applicable)
        Active AMR
    4
    3
        Active AMR + Borderline CMR
    0
    1
        Active AMR + CMR
    1
    1
        Chronic Active AMR + Borderline CMR
    1
    1
        Chronic Active AMR + CMR
    1
    0
        Chronic Active AMR
    4
    2
        Borderline CMR
    0
    1
        CMR
    1
    0
        No rejection
    5
    1
        Missing data
    2
    0
    No statistical analyses for this end point

    Secondary: Proportion of Patients With Different Types of Kidney Histopathology at Day 180

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    End point title
    		 Proportion of Patients With Different Types of Kidney Histopathology at Day 180
    End point description
    Kidney biopsies were assessed according to the Banff (2017 or 2019) criteria at screening (baseline), Day 29, and Day 180.
    End point type
    Secondary
    End point timeframe
    Day 180
    End point values
    		 Imlifidase Plasma exchange (PE)
    Number of subjects analysed
    19
    10
    Units: Patients
    number (not applicable)
        Active AMR
    2
    2
        Active AMR + CMR
    1
    0
        Chronic Active AMR + Borderline CMR
    2
    0
        Chronic Active AMR + CMR
    1
    0
        Chronic Active AMR
    5
    5
        CMR
    0
    1
        No rejection
    2
    2
        Missing data
    6
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs were collected for 6 months (from signed ICF until end of study including the follow-up period). AEs after start of trial treatment and within the time of residual drug effect i.e. 28 days are classified as treatment emergent AEs (TEAEs).
    Adverse event reporting additional description
    AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. The reported non-serious AEs consists of TEAEs irrespective of relationship to treatment. The reported SAEs covers the whole study. 6 SAEs were treatment related. The SAE with fatal outcome occurred Day 176.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Imlifidase - Safety Analysis Set
    Reporting group description
    		 The safety analysis dataset comprises data from all treated patients and was analysed according to the actual treatment received.

    Reporting group title
    PE - Safety Analysis Set
    Reporting group description
    		 The safety analysis dataset comprises data from all treated patients and was analysed according to the actual treatment received.

    Serious adverse events
    		 Imlifidase - Safety Analysis Set PE - Safety Analysis Set
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 19 (68.42%)
    8 / 10 (80.00%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    1
    0
    Injury, poisoning and procedural complications
    Arteriovenous fistula site complication
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complications of transplanted kidney
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal lymphocele
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shunt thrombosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leukocytosis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrogenic anaemia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Device related thrombosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Kidney transplant rejection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal transplant failure
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transplant rejection
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    5 / 19 (26.32%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder tamponade
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postrenal failure
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscle haemorrhage
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bacterial pyelonephritis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Corona virus infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia pyelonephritis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Imlifidase - Safety Analysis Set PE - Safety Analysis Set
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    17 / 19 (89.47%)
    10 / 10 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Hypotension
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    0
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Catheter site pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Chest pain
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Fatigue
         subjects affected / exposed
    3 / 19 (15.79%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    Gait disturbance
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Malaise
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Oedema peripheral
         subjects affected / exposed
    3 / 19 (15.79%)
    1 / 10 (10.00%)
         occurrences all number
    3
    1
    Pyrexia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Immune system disorders
    Transplant rejection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 10 (10.00%)
         occurrences all number
    1
    1
    Pulmonary congestion
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Depressed mood
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Feeling of despair
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Panic attack
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Sleep disorder
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Investigations
    Acid base balance abnormal
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Antibody test positive
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    BK polyomavirus test positive
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    3 / 19 (15.79%)
    1 / 10 (10.00%)
         occurrences all number
    3
    3
    Blood glucose fluctuation
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Blood triglycerides increased
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 19 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    0
    2
    Immunosuppressant drug level increased
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Overdose
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Renal lymphocele
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    2 / 19 (10.53%)
    1 / 10 (10.00%)
         occurrences all number
    4
    1
    Tremor
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Leukocytosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Leukopenia
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 10 (10.00%)
         occurrences all number
    1
    1
    Lymphopenia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    4 / 19 (21.05%)
    1 / 10 (10.00%)
         occurrences all number
    5
    1
    Thrombotic microangiopathy
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Tinnitus
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Visual impairment
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Abdominal hernia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Ascites
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Diarrhoea
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 10 (10.00%)
         occurrences all number
    2
    1
    Dyspepsia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Flatulence
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Food poisoning
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    Vomiting
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Hepatocellular injury
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Dysuria
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Incontinence
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Proteinuria
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Bone pain
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Muscle spasms
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 10 (10.00%)
         occurrences all number
    1
    1
    Myalgia
         subjects affected / exposed
    1 / 19 (5.26%)
    1 / 10 (10.00%)
         occurrences all number
    1
    1
    Pain in extremity
         subjects affected / exposed
    2 / 19 (10.53%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Infections and infestations
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Sinusitis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Calcium deficiency
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Dehydration
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Dyslipidaemia
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Folate deficiency
         subjects affected / exposed
    0 / 19 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    4 / 19 (21.05%)
    2 / 10 (20.00%)
         occurrences all number
    10
    2
    Hyperkalaemia
         subjects affected / exposed
    3 / 19 (15.79%)
    4 / 10 (40.00%)
         occurrences all number
    3
    4
    Hyperphosphataemia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 19 (5.26%)
    2 / 10 (20.00%)
         occurrences all number
    1
    2
    Hypomagnesaemia
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Metabolic acidosis
         subjects affected / exposed
    1 / 19 (5.26%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Mar 2020
    Amendment 1, substantial, introduced changes (Austria, Australia, France, US) • Allowed for a kidney biopsy performed within standard of care to be used for inclusion. • Clarified inclusion criteria #5 by adding chronic active AMR. • Clarified that the 3 latest creatinine values prior to the current AMR should be collected. • Extension of trial duration by 8 months. • Benefit/risk section was updated with new number for infusion reactions according to the latest version of IB.
    06 Oct 2020
    Amendment 2, substantial introduced the following changes (Austria, Australia, France, US): • Ensured that patients with asymptomatic Covid-19 were not included in the trial • Serum sickness was no longer classified as a risk • Thrombocytopenic purpura (TTP) was defined as a contraindication and exclusion criterion • Extension of trial duration by 9 months

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    07 Apr 2020
    Due to the COVID-19 pandemic the patient recruitment was temporary halted. During the last quarter of 2020 and during 2021 and 2022 (US sites only) on‑site monitoring visits were not accepted due to the Covid-19 pandemic. Source data verification was performed to the extent possible and was fully completed when monitors could visit the sites again.
    01 Dec 2020

    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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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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