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    Clinical Trial Results:
    A partially-blinded, active-controlled, multicenter, randomized study evaluating efficacy, safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) of an anti-CD40 monoclonal antibody, CFZ533, in de novo and maintenance kidney transplant recipients (CIRRUS I) Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.nov for complete trial results.

    Summary
    EudraCT number
    		 2017-003607-22
    Trial protocol
    		 SE   NL   NO   FR   GB   DE   ES   CZ   BE   HU   SK   LV   LT   IT   HR  
    Global end of trial date
    29 Oct 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Dec 2022
    First version publication date
    15 Dec 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CCFZ533A2201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03663335
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma, AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma, AG, 41 613241111, novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma, AG, 41 613241111, novartis.email@novartis.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
    29 Oct 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Oct 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Primary objectives: Cohort 1: To demonstrate that CFZ533 600 mg and/or 300 mg bi-weekly (Q2W) subcutaneous (SC) are non-inferior to a Tacrolimus (TAC)-based regimen with respect to the proportion of patients who experience composite efficacy failure event (biopsy proven acute rejection (BPAR), graft loss, or death) over 12 months post-transplantation. Cohort 2: To demonstrate that CFZ533 450 mg bi-weekly (Q2W) subcutaneous (SC) is non-inferior to a TAC-based regimen with respect to the proportion of patients who experience composite efficacy failure event (biopsy proven acute rejection (BPAR), graft loss, or death) over 12 months post-conversion.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Nov 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 19
    Country: Number of subjects enrolled
    Australia: 9
    Country: Number of subjects enrolled
    Belgium: 19
    Country: Number of subjects enrolled
    Brazil: 53
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    Czechia: 14
    Country: Number of subjects enrolled
    France: 56
    Country: Number of subjects enrolled
    Germany: 20
    Country: Number of subjects enrolled
    Hungary: 7
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Japan: 33
    Country: Number of subjects enrolled
    Korea, Republic of: 3
    Country: Number of subjects enrolled
    Latvia: 3
    Country: Number of subjects enrolled
    Netherlands: 37
    Country: Number of subjects enrolled
    Norway: 9
    Country: Number of subjects enrolled
    Spain: 36
    Country: Number of subjects enrolled
    Sweden: 7
    Country: Number of subjects enrolled
    Switzerland: 2
    Country: Number of subjects enrolled
    United Kingdom: 8
    Country: Number of subjects enrolled
    United States: 61
    Worldwide total number of subjects
    403
    EEA total number of subjects
    214
    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)
    357
    From 65 to 84 years
    46
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients were enrolled at 74 sites. 403 patients were randomized.

    Pre-assignment
    Screening details
    		 This study comprised of a screening period.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS
    Arm description
    		 Eligible patients were randomized to CFZ533 600 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 600 mg sc (2 injections of 2 mL CFZ533 at 150 mg/mL) Q2W, up to a planned Month 59.5 visit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mycophenolate Mofetil (MMF)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet, Capsule, Solution for injection/infusion
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Per local practice, 250 mg or 500 mg taken orally or 500 mg taken intravenously.

    Investigational medicinal product name
    Iscalimab
    Investigational medicinal product code
    CFZ533
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use, Intravenous use
    Dosage and administration details
    CFZ533 600 mg was was first administered intravenously and subcutaneously thereafter.

    Investigational medicinal product name
    Basiliximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lyophilized solution taken intravenously

    Investigational medicinal product name
    Rabbit anti-thymocyte globulin (rATG)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lyophilized vial taken intravenously

    Investigational medicinal product name
    Corticosteroids
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Injection
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Taken either orally or intravenously.

    Arm title
    		 Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS
    Arm description
    		 Eligible patients were randomized to CFZ533 300 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 300 mg sc (1 injection of 2 mL CFZ533 at 150 mg/mL, and 1 injection of 2 mL of the generic placebo) sc, Q2W, up to a planned Month 59.5 visit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Iscalimab
    Investigational medicinal product code
    CFZ533
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    CFZ533 300 mg was first administered intravenously and subcutaneously thereafter.

    Investigational medicinal product name
    Mycophenolate Mofetil (MMF)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet, Capsule, Solution for injection/infusion
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    Per local practice, 250 mg or 500 mg taken orally or 500 mg taken intravenously.

    Investigational medicinal product name
    Corticosteroids
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Injection
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Taken either orally or intravenously.

    Investigational medicinal product name
    Basiliximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lyophilized solution taken intravenously

    Investigational medicinal product name
    Rabbit anti-thymocyte globulin (rATG)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lyophilized vial taken intravenously

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Solution taken subcutaneously and was used for blinding of the CFZ533 doses

    Arm title
    		 Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS
    Arm description
    		 Patients randomized to the TAC control arm were initiated on a TAC-based regimen with MMF and corticosteroids.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Tacrolimus (TAC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Standard of care immunosuppressive regimen

    Investigational medicinal product name
    Corticosteroids
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Injection
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Taken either orally or intravenously.

    Investigational medicinal product name
    Basiliximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lyophilized solution taken intravenously

    Investigational medicinal product name
    Rabbit anti-thymocyte globulin (rATG)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lyophilized vial taken intravenously

    Investigational medicinal product name
    Mycophenolate Mofetil (MMF)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet, Capsule, Solution for injection/infusion
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    Per local practice, 250 mg or 500 mg taken orally or 500 mg taken intravenously.

    Arm title
    		 Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS
    Arm description
    		 Eligible patients who were 6 to 24 months post renal transplantation and were on a stable regimen containing TAC+MMF/Enteric-coated mycophenolate sodium (EC-MPS)±CS were randomized to CFZ533 450 mg sc Q2W. On Day 1, patients randomized to Arm 1 were administered the 1st dose of CFZ533 at 30 mg/kg IV, concomitantly with MMF/EC-MPS and 50% of the current TAC dose. At Day 15, CFZ533 was administered sc 450 mg (1 injection of 2 mL & 1 injection of 1 mL CFZ533 at 150 mg/mL) concomitantly with MMF/EC-MPS, and TAC reduced by a further 50%. By Day 29, patients were fully tapered off their TAC. Subsequent doses of 450 mg sc Q2W, were administered in combination with MMF/EC-MPS with or without corticosteroids, up to Month 59.5 visit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Iscalimab
    Investigational medicinal product code
    CFZ533
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    CFZ533 450 mg was first administered intravenously and subcutaneously thereafter.

    Investigational medicinal product name
    Mycophenolate Mofetil (MMF)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet, Capsule, Solution for injection/infusion
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Per local practice, 250 mg or 500 mg taken orally or 500 mg taken intravenously.

    Investigational medicinal product name
    Corticosteroids
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Injection
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Taken either orally or intravenously.

    Investigational medicinal product name
    Enteric-coated mycophenolate sodium (EC-MPS)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet that was taken orally

    Arm title
    		 Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Arm description
    		 Patients received TAC-based regimen throughout the study.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Corticosteroids
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Injection
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    Dose was administered based on Investigator determination.

    Investigational medicinal product name
    Enteric-coated mycophenolate sodium (EC-MPS)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet that was taken orally

    Investigational medicinal product name
    Mycophenolate Mofetil (MMF)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet, Capsule, Solution for injection/infusion
    Routes of administration
    Intravenous use, Oral use
    Dosage and administration details
    Per local practice, 250 mg or 500 mg taken orally or 500 mg taken intravenously.

    Investigational medicinal product name
    Tacrolimus (TAC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Standard of care immunosuppressive regimen

    Number of subjects in period 1
    		Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Started
    108
    109
    74
    70
    42
    Completed
    0
    0
    0
    0
    0
    Not completed
    108
    109
    74
    70
    42
         Adverse event, serious fatal
    9
    1
    2
    1
    2
         Physician decision
    -
    -
    -
    -
    1
         Study terminated by Sponsor
    71
    73
    53
    60
    33
         Adverse event, non-fatal
    8
    19
    3
    6
    -
         Subject decision
    3
    5
    3
    -
    4
         Unsatisfactory therapeutic effect
    5
    2
    1
    -
    -
         Patient not continuing after Month12
    12
    9
    11
    3
    2
         Lost to follow-up
    -
    -
    1
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS
    Reporting group description
    		 Eligible patients were randomized to CFZ533 600 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 600 mg sc (2 injections of 2 mL CFZ533 at 150 mg/mL) Q2W, up to a planned Month 59.5 visit.

    Reporting group title
    Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS
    Reporting group description
    		 Eligible patients were randomized to CFZ533 300 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 300 mg sc (1 injection of 2 mL CFZ533 at 150 mg/mL, and 1 injection of 2 mL of the generic placebo) sc, Q2W, up to a planned Month 59.5 visit.

    Reporting group title
    Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS
    Reporting group description
    		 Patients randomized to the TAC control arm were initiated on a TAC-based regimen with MMF and corticosteroids.

    Reporting group title
    Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS
    Reporting group description
    		 Eligible patients who were 6 to 24 months post renal transplantation and were on a stable regimen containing TAC+MMF/Enteric-coated mycophenolate sodium (EC-MPS)±CS were randomized to CFZ533 450 mg sc Q2W. On Day 1, patients randomized to Arm 1 were administered the 1st dose of CFZ533 at 30 mg/kg IV, concomitantly with MMF/EC-MPS and 50% of the current TAC dose. At Day 15, CFZ533 was administered sc 450 mg (1 injection of 2 mL & 1 injection of 1 mL CFZ533 at 150 mg/mL) concomitantly with MMF/EC-MPS, and TAC reduced by a further 50%. By Day 29, patients were fully tapered off their TAC. Subsequent doses of 450 mg sc Q2W, were administered in combination with MMF/EC-MPS with or without corticosteroids, up to Month 59.5 visit.

    Reporting group title
    Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Reporting group description
    		 Patients received TAC-based regimen throughout the study.

    Reporting group values
    		 Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS Total
    Number of subjects
    		 108 109 74 70 42 403
    Age Categorical
    Units: Participants
        < 60 years
    		 86 79 54 53 32 304
        >= 60 6years
    		 22 30 20 17 10 99
    Sex: Female, Male
    Units: Participants
        Female
    		 34 32 14 18 14 112
        Male
    		 74 77 60 52 28 291
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 84 86 59 47 32 308
        Black or African American
    		 14 6 6 3 4 33
        Asian: Indian
    		 2 0 0 1 0 3
        Asian: Japanese
    		 4 12 3 12 4 35
        Asian: Korean
    		 1 0 0 3 0 4
        Multiple
    		 3 4 3 2 1 13
        American Indian or Alaskan Native
    		 0 0 1 0 0 1
        Asian - Other
    		 0 1 2 1 1 5
        Other - Unknown
    		 0 0 0 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS
    Reporting group description
    		 Eligible patients were randomized to CFZ533 600 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 600 mg sc (2 injections of 2 mL CFZ533 at 150 mg/mL) Q2W, up to a planned Month 59.5 visit.

    Reporting group title
    Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS
    Reporting group description
    		 Eligible patients were randomized to CFZ533 300 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 300 mg sc (1 injection of 2 mL CFZ533 at 150 mg/mL, and 1 injection of 2 mL of the generic placebo) sc, Q2W, up to a planned Month 59.5 visit.

    Reporting group title
    Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS
    Reporting group description
    		 Patients randomized to the TAC control arm were initiated on a TAC-based regimen with MMF and corticosteroids.

    Reporting group title
    Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS
    Reporting group description
    		 Eligible patients who were 6 to 24 months post renal transplantation and were on a stable regimen containing TAC+MMF/Enteric-coated mycophenolate sodium (EC-MPS)±CS were randomized to CFZ533 450 mg sc Q2W. On Day 1, patients randomized to Arm 1 were administered the 1st dose of CFZ533 at 30 mg/kg IV, concomitantly with MMF/EC-MPS and 50% of the current TAC dose. At Day 15, CFZ533 was administered sc 450 mg (1 injection of 2 mL & 1 injection of 1 mL CFZ533 at 150 mg/mL) concomitantly with MMF/EC-MPS, and TAC reduced by a further 50%. By Day 29, patients were fully tapered off their TAC. Subsequent doses of 450 mg sc Q2W, were administered in combination with MMF/EC-MPS with or without corticosteroids, up to Month 59.5 visit.

    Reporting group title
    Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Reporting group description
    		 Patients received TAC-based regimen throughout the study.

    Subject analysis set title
    Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible patients were randomized to CFZ533 600 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 600 mg sc (2 injections of 2 mL CFZ533 at 150 mg/mL) Q2W, up to a planned Month 59.5 visit.

    Subject analysis set title
    Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients randomized to the TAC control arm were initiated on a TAC-based regimen with MMF and corticosteroids.

    Subject analysis set title
    Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Eligible patients who were 6 to 24 months post renal transplantation and were on a stable regimen containing TAC+MMF/Enteric-coated mycophenolate sodium (EC-MPS)±CS were randomized to CFZ533 450 mg sc Q2W. On Day 1, patients randomized to Arm 1 were administered the 1st dose of CFZ533 at 30 mg/kg IV, concomitantly with MMF/EC-MPS and 50% of the current TAC dose. At Day 15, CFZ533 was administered sc 450 mg (1 injection of 2 mL & 1 injection of 1 mL CFZ533 at 150 mg/mL) concomitantly with MMF/EC-MPS, and TAC reduced by a further 50%. By Day 29, patients were fully tapered off their TAC. Subsequent doses of 450 mg sc Q2W, were administered in combination with MMF/EC-MPS with or without corticosteroids, up to Month 59.5 visit.

    Subject analysis set title
    Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients received TAC-based regimen throughout the study.

    Primary: Percentage of participants with composite efficacy failure event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) over 12 months post-transplantation (Cohort 1)

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    End point title
    		 Percentage of participants with composite efficacy failure event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) over 12 months post-transplantation (Cohort 1) [1]
    End point description
    The composite efficacy failure event is defined as any of the following: (1) biopsy-proven acute rejection (BPAR) or (2) graft loss or (3) death. BPAR (BANFF ≥ 1A) is based on the central and adjudicated assessments. Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted. If the participant underwent allograft nephrectomy prior to start of permanent dialysis, the day of the nephrectomy was day of graft loss.
    End point type
    Primary
    End point timeframe
    12 Months
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The statistical analysis is only being presented here for arms in this cohort (Cohort 1) and not for all arms in the baseline period.
    End point values
    		 Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS
    Number of subjects analysed
    66
    70
    41
    Units: Percentage of participants
        number (not applicable)
    60.6
    38.6
    22.0
    Statistical analysis title
    		 CFZ533 300 mg vs. TAC
    Comparison groups
    Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS v Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Rate Difference
    Point estimate
    5.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.67
         upper limit
    		 16.9
    Notes
    [2] - less than a non-inferiority (NI) margin of 20% in the de novo cohort (Cohort 1)
    Statistical analysis title
    		 CFZ533 600 mg vs. TAC
    Comparison groups
    Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS v Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 Rate Difference
    Point estimate
    15.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.86
         upper limit
    		 27.74
    Notes
    [3] - less than a non-inferiority (NI) margin of 20% in the de novo cohort (Cohort 1)

    Primary: Percentage of participants with composite efficacy failure event (BPAR, Graft Loss or Death) over 12 months post-conversion (Cohort 2)

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    End point title
    		 Percentage of participants with composite efficacy failure event (BPAR, Graft Loss or Death) over 12 months post-conversion (Cohort 2) [4]
    End point description
    The composite efficacy failure event is defined as any of the following: (1) biopsy-proven acute rejection (BPAR) or (2) graft loss or (3) death. BPAR (BANFF ≥ 1A) is based on the central and adjudicated assessments. Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted. If the participant underwent allograft nephrectomy prior to start of permanent dialysis, the day of the nephrectomy was day of graft loss.
    End point type
    Primary
    End point timeframe
    12 Months
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The statistical analysis is only being presented here for arms in this cohort (Cohort 2) and not for all arms in the baseline period.
    End point values
    		 Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Number of subjects analysed
    34
    18
    Units: Percentage of participants
        number (not applicable)
    14.7
    11.1
    Statistical analysis title
    		 CFZ533 450 mg vs TAC
    Comparison groups
    Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS v Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    Parameter type
    		 Rate Difference
    Point estimate
    -1.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.24
         upper limit
    		 11.39
    Notes
    [5] - less than a non-inferiority (NI) margin of 20% in the de novo cohort (Cohort 1)

    Secondary: Cohort 1: Mean estimated Glomerular Filtration Rate (eGFR) ((MDR4) at 12 months post-transplantation

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    End point title
    		 Cohort 1: Mean estimated Glomerular Filtration Rate (eGFR) ((MDR4) at 12 months post-transplantation [6]
    End point description
    In the de novo population (Cohort 1), the mean eGFR at Month 12 post-transplantation was the endpoint of interest. Estimated GFR using central laboratory serum creatinine values was calculated using the MDRD-4 formula.
    End point type
    Secondary
    End point timeframe
    12 months
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The statistical analysis is only being presented here for arms in this cohort (Cohort 1) and not for all arms in the baseline period.
    End point values
    		 Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS
    Number of subjects analysed
    58
    58
    51
    Units: mL/min/1.73m**2
        arithmetic mean (standard error)
    58.83 ( 1.971 )
    60.63 ( 1.976 )
    54.12 ( 2.101 )
    Statistical analysis title
    		 CFZ533 600 mg vs TAC (mean eGFR)
    Comparison groups
    Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS v Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.103
    Method
    		 ANOVA
    Parameter type
    		 mean difference
    Point estimate
    4.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.96
         upper limit
    		 10.38
    Variability estimate
    Standard deviation
    Dispersion value
    2.873
    Statistical analysis title
    		 CFZ533 300 mg vs TAC (mean eGFR)
    Comparison groups
    Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS v Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.025
    Method
    		 ANOVA
    Parameter type
    		 mean difference
    Point estimate
    6.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 12.18
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.875

    Secondary: Cohort 2: Mean change in estimated Glomerular Filtration Rate (eGFR) ((MDR4) at 12 months post-conversion

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    End point title
    		 Cohort 2: Mean change in estimated Glomerular Filtration Rate (eGFR) ((MDR4) at 12 months post-conversion [7]
    End point description
    In the maintenance population (Cohort 2), a baseline kidney function and the mean change from baseline at Month 12 post-conversion of eGFR was the endpoint of interest. Estimated GFR using central laboratory serum creatinine values was calculated using the MDRD-4 formula.
    End point type
    Secondary
    End point timeframe
    12 months
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The statistical analysis is only being presented here for arms in this cohort (Cohort 2) and not for all arms in the baseline period.
    End point values
    		 Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Number of subjects analysed
    39
    27
    Units: mL/min/1.73m^2
        arithmetic mean (standard error)
    4.30 ( 1.722 )
    1.42 ( 1.866 )
    Statistical analysis title
    		 CFZ533 450 mg vs TAC (mean change in eGFR)
    Comparison groups
    Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS v Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.153
    Method
    		 ANOVA
    Parameter type
    		 mean change difference
    Point estimate
    2.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 6.85
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.987

    Secondary: Free CFZ533 plasma concentrations over time (Cohort 1)

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    End point title
    		 Free CFZ533 plasma concentrations over time (Cohort 1) [8]
    End point description
    Pharmacokinetics were determined for free CFZ533 plasma concentrations during the treatment period.
    End point type
    Secondary
    End point timeframe
    60 Months
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS
    Number of subjects analysed
    109
    110
    70
    Units: µg/mL
    arithmetic mean (standard deviation)
        Day 1 Pre-dose (n = 96, 94, 0)
    0.00 ( 0.000 )
    0.00 ( 0.000 )
    999 ( 999 )
        Day 1 post-dose (n = 106, 106, 0)
    441.67 ( 246.474 )
    471.20 ( 222.169 )
    999 ( 999 )
        Day 5 pre-dose (n = 95, 97, 0)
    205.16 ( 77.632 )
    231.93 ( 102.947 )
    999 ( 999 )
        Day 5 post-dose (n = 98, 99, 0)
    502.32 ( 186.159 )
    502.48 ( 211.592 )
    999 ( 999 )
        Day 15 pre-dose (n = 104, 98, 0)
    242.99 ( 83.780 )
    251.17 ( 92.466 )
    999 ( 999 )
        Day 29 pre-dose (n = 98, 95, 0)
    187.38 ( 79.884 )
    197.47 ( 74.937 )
    999 ( 999 )
        Month 1.5 pre-dose (n = 93, 93, 0)
    122.80 ( 38.604 )
    172.84 ( 67.444 )
    999 ( 999 )
        Month 2 pre-dose (n = 89, 90, 0)
    102.52 ( 33.798 )
    155.68 ( 64.661 )
    999 ( 999 )
        Month 2.5 pre-dose (n = 86, 88, 0)
    85.21 ( 34.835 )
    151.81 ( 58.367 )
    999 ( 999 )
        Month 3 pre-dose (n = 84, 83, 0)
    86.16 ( 35.463 )
    147.62 ( 51.971 )
    999 ( 999 )
        Month 4 pre-dose (n = 81, 72, 0)
    68.72 ( 27.269 )
    159.58 ( 70.382 )
    999 ( 999 )
        Month 6 pre-dose (n = 69, 77, 0)
    73.27 ( 35.126 )
    161.21 ( 63.195 )
    999 ( 999 )
        Month 8 pre-dose (n = 60, 64, 0)
    71.92 ( 33.683 )
    151.34 ( 52.778 )
    999 ( 999 )
        Month 10 pre-dose (n = 56, 58, 0)
    62.55 ( 31.199 )
    141.18 ( 46.999 )
    999 ( 999 )
        Moth 12 pre-dose (n = 51, 55, 0)
    56.81 ( 30.717 )
    148.71 ( 62.106 )
    999 ( 999 )
        Month 15 pre-dose(n = 36, 40, 0)
    48.37 ( 20.604 )
    149.86 ( 58.888 )
    999 ( 999 )
        Month 18 pre-dose (n = 43, 37, 0)
    49.68 ( 31.768 )
    122.24 ( 54.056 )
    999 ( 999 )
        Month 21 pre-dose (n = 40, 32, 0)
    59.96 ( 36.583 )
    132.51 ( 65.146 )
    999 ( 999 )
        Month 24 pre-dose (n = 36, 33, 0)
    60.96 ( 31.988 )
    139.55 ( 53.177 )
    999 ( 999 )
        Month 30 pre-dose (n = 11, 12, 0)
    56.63 ( 23.195 )
    140.80 ( 47.339 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Free CFZ533 plasma concentrations over time (Cohort 2)

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    End point title
    		 Free CFZ533 plasma concentrations over time (Cohort 2) [9]
    End point description
    Pharmacokinetics were determined for free CFZ533 plasma concentrations during the treatment period.
    End point type
    Secondary
    End point timeframe
    60 Months
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Number of subjects analysed
    70
    40
    Units: µg/mL
    arithmetic mean (standard deviation)
        Day 1 Pre-dose (n = 67, 0)
    0.00 ( 0.000 )
    999 ( 999 )
        Day 1 post-dose (n = 68, 0)
    681.59 ( 698.086 )
    999 ( 999 )
        Day 15 pre-dose (n = 67, 0)
    181.81 ( 72.297 )
    999 ( 999 )
        Day 29 pre-dose (n = 65, 0)
    147.56 ( 43.749 )
    999 ( 999 )
        Month 1.5 pre-dose (n = 65, 0)
    127.55 ( 39.794 )
    999 ( 999 )
        Month 2 pre-dose (n = 61, 0)
    121.81 ( 44.801 )
    999 ( 999 )
        Month 2.5 pre-dose (n = 66, 0)
    114.53 ( 44.759 )
    999 ( 999 )
        Month 3 pre-dose (n = 63, 0)
    104.40 ( 42.563 )
    999 ( 999 )
        Month 4 pre-dose (n = 62, 0)
    108.61 ( 51.790 )
    999 ( 999 )
        Month 6 pre-dose (n = 56, 0)
    112.14 ( 46.932 )
    999 ( 999 )
        Month 8 pre-dose (n = 51, 0)
    118.08 ( 42.868 )
    999 ( 999 )
        Month 10 pre-dose (n = 41, 0)
    106.98 ( 53.798 )
    999 ( 999 )
        Moth 12 pre-dose (n = 37, 0)
    111.05 ( 54.629 )
    999 ( 999 )
        Month 15 pre-dose(n = 25, 0)
    104.11 ( 67.744 )
    999 ( 999 )
        Month 18 pre-dose (n = 24, 0)
    115.59 ( 66.227 )
    999 ( 999 )
        Month 21 pre-dose (n = 24, 0)
    116.89 ( 53.953 )
    999 ( 999 )
        Month 24 pre-dose (n = 18, 0)
    111.03 ( 39.901 )
    999 ( 999 )
        Month 30 pre-dose (n = 3, 0)
    132.97 ( 65.132 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Semi-quantiative analysis of anti-CFZ533 antibodes in plasma (CFZ533 treated patients only) (Cohort 1)

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    End point title
    		 Semi-quantiative analysis of anti-CFZ533 antibodes in plasma (CFZ533 treated patients only) (Cohort 1) [10]
    End point description
    The presence of anti-CFZ533 antibodies was assessed using screening and confirmatory assays.
    End point type
    Secondary
    End point timeframe
    60 Months
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS
    Number of subjects analysed
    109
    110
    Units: Participants
        Subject with an on-study result
    108
    109
        Binding antibody positive at any time
    0
    2
        Subject with a result at baseline
    101
    104
        Binding antibody positive at or before baseline
    0
    0
        Subject with a post-baseline result
    103
    102
        ADA positive post-dose with positive result at BL
    0
    0
        ADA positive post-dose with negative result at BL
    0
    2
    No statistical analyses for this end point

    Secondary: Semi-quantiative analysis of anti-CFZ533 antibodes in plasma (CFZ533 treated patients only) (Cohort 2)

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    End point title
    		 Semi-quantiative analysis of anti-CFZ533 antibodes in plasma (CFZ533 treated patients only) (Cohort 2) [11]
    End point description
    The presence of anti-CFZ533 antibodies was assessed using screening and confirmatory assays.
    End point type
    Secondary
    End point timeframe
    60 Months
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS
    Number of subjects analysed
    70
    Units: Participants
        Subject with an on-study result
    70
        Binding antibody positive at any time
    0
        Subject with a result at baseline
    68
        Binding antibody positive at or before baseline
    0
        Subject with a post-baseline result
    69
        ADA positive post-dose with positive result at BL
    0
        ADA positive post-dose with -ve or no result at BL
    0
    No statistical analyses for this end point

    Post-hoc: All Collected Deaths

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    End point title
    		 All Collected Deaths [12]
    End point description
    On-treatment deaths were collected from start of First Patient First Treatment (FPFT) up to last dose of assigned treatment, for a maximum duration of approx. 2.9 years. Randomized but not treated deaths were collected after randomization but before treatment with study drug. Deaths post-treatment survival follow-up were collected after last dose of assigned treatment until end of study participation. Deaths Post-study participation were collected after patients completed trial participation but before LPLV of the study.
    End point type
    Post-hoc
    End point timeframe
    from FPFT to last on-treatment death (76 weeks), from FPFT to LPLV (2.9 years)
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    		 Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + MMF + CS Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + MMF + CS Arm 3/Cohort 1 (De Novo Cohort): TAC + MMF + CS Arm 1/Cohort 2 Maintenance Cohort): CFZ533 450 mg + MMF ± CS Arm 2/Cohort 2 (Maintenance Cohort): TAC+ MMF ± CS
    Number of subjects analysed
    108
    109
    74
    70
    42
    Units: Participants
        Total Deaths
    9
    2
    2
    2
    2
        Deaths On-treatment
    2
    0
    1
    0
    0
        Deaths Post-treatment
    7
    1
    0
    1
    2
        Deaths - Randomized, not treated
    0
    0
    1
    0
    0
        Deaths Post-study participation
    0
    1
    0
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs were reported from first dose of study treatment until LPLV, up to approx. 2.9 years.
    Adverse event reporting additional description
    Adverse Events (AE): Any sign or symptom that occurs during treatment up to end of study, approx. 2.9 years, for a median duration of exposure to CFZ533 600 mg of 365.5 days, to CFZ533 300 mg of 365 days and to TAC of 414 days (Cohort 1). The median duration of exposure to CFZ533 450 mg was 372 days & to TAC was 389.5 days (Cohort 2).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    De Novo Cohort: CFZ533 300 mg + MMF + CS
    Reporting group description
    		 De Novo Cohort: CFZ533 300 mg + MMF + CS

    Reporting group title
    De Novo Cohort: CFZ533 600 mg + MMF + CS
    Reporting group description
    		 De Novo Cohort: CFZ533 600 mg + MMF + CS

    Reporting group title
    Maintenance Cohort: CFZ533 450 mg + MMF +/- CS
    Reporting group description
    		 Maintenance Cohort: CFZ533 450 mg + MMF +/- CS

    Reporting group title
    Maintenance Cohort: TAC + MMF +/- CS
    Reporting group description
    		 Maintenance Cohort: TAC + MMF +/- CS

    Reporting group title
    De Novo Cohort: TAC + MMF + CS
    Reporting group description
    		 De Novo Cohort: TAC + MMF + CS

    Serious adverse events
    		 De Novo Cohort: CFZ533 300 mg + MMF + CS De Novo Cohort: CFZ533 600 mg + MMF + CS Maintenance Cohort: CFZ533 450 mg + MMF +/- CS Maintenance Cohort: TAC + MMF +/- CS De Novo Cohort: TAC + MMF + CS
    Total subjects affected by serious adverse events
         subjects affected / exposed
    76 / 109 (69.72%)
    71 / 108 (65.74%)
    25 / 70 (35.71%)
    11 / 42 (26.19%)
    39 / 73 (53.42%)
         number of deaths (all causes)
    1
    9
    1
    2
    1
         number of deaths resulting from adverse events
    1
    2
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian adenoma
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    2 / 42 (4.76%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Arterial stenosis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Arterial thrombosis
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Hypotension
         subjects affected / exposed
    2 / 109 (1.83%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iliac artery stenosis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Shock haemorrhagic
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Subclavian artery stenosis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicose ulceration
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Venous thrombosis
         subjects affected / exposed
    2 / 109 (1.83%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    2 / 109 (1.83%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Fatigue
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    General physical health deterioration
         subjects affected / exposed
    2 / 109 (1.83%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hernia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Hyperthermia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Inflammation
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 109 (4.59%)
    4 / 108 (3.70%)
    4 / 70 (5.71%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    3 / 7
    0 / 4
    1 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anti-neutrophil cytoplasmic antibody positive vasculitis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Transplant rejection
         subjects affected / exposed
    10 / 109 (9.17%)
    16 / 108 (14.81%)
    2 / 70 (2.86%)
    0 / 42 (0.00%)
    6 / 73 (8.22%)
         occurrences causally related to treatment / all
    6 / 11
    10 / 18
    2 / 2
    0 / 0
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Acquired hydrocele
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Prostatitis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Cough
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Hypoxia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 109 (2.75%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 109 (0.00%)
    4 / 108 (3.70%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood glucose increased
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Troponin increased
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Weight decreased
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Complications of transplanted kidney
         subjects affected / exposed
    3 / 109 (2.75%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delayed graft function
         subjects affected / exposed
    3 / 109 (2.75%)
    6 / 108 (5.56%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    4 / 73 (5.48%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 0
    0 / 0
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Graft complication
         subjects affected / exposed
    1 / 109 (0.92%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Graft ischaemia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Graft loss
         subjects affected / exposed
    3 / 109 (2.75%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Nerve injury
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Post procedural haematoma
         subjects affected / exposed
    0 / 109 (0.00%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative lymphocele
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Postoperative wound complication
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural shock
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Transplant dysfunction
         subjects affected / exposed
    0 / 109 (0.00%)
    4 / 108 (3.70%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 5
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 109 (0.00%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Atrial fibrillation
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Cardiac failure
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Myocardial infarction
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Anosmia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Cerebrovascular accident
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Guillain-Barre syndrome
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Headache
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive encephalopathy
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intensive care unit acquired weakness
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Ischaemic neuropathy
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Mononeuropathy multiplex
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Quadrantanopia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiculitis brachial
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Seizure
         subjects affected / exposed
    0 / 109 (0.00%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 109 (1.83%)
    2 / 108 (1.85%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eosinophilia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    2 / 109 (1.83%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    4 / 109 (3.67%)
    1 / 108 (0.93%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    3 / 4
    1 / 1
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy mediastinal
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Lymphopenia
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 109 (0.92%)
    2 / 108 (1.85%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Photophobia
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Retinal detachment
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uveitis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Ascites
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Colitis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 109 (1.83%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Food poisoning
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Ileus
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Inguinal hernia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Stasis dermatitis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    4 / 109 (3.67%)
    3 / 108 (2.78%)
    1 / 70 (1.43%)
    1 / 42 (2.38%)
    7 / 73 (9.59%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 3
    1 / 1
    0 / 1
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Glomerulonephritis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Haematuria
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perinephric collection
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal artery stenosis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Renal cyst
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Renal cyst haemorrhage
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    1 / 42 (2.38%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 109 (0.92%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal infarct
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal ischaemia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Renal vein thrombosis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Subcapsular renal haematoma
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Tubulointerstitial nephritis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Ureteric stenosis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary fistula
         subjects affected / exposed
    0 / 109 (0.00%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    2 / 109 (1.83%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract disorder
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Goitre
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Hyperaldosteronism
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperparathyroidism
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperparathyroidism secondary
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Myalgia
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Pain in extremity
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Adenovirus infection
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    BK virus infection
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Bronchitis
         subjects affected / exposed
    2 / 109 (1.83%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    1 / 42 (2.38%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    3 / 109 (2.75%)
    5 / 108 (4.63%)
    1 / 70 (1.43%)
    2 / 42 (4.76%)
    3 / 73 (4.11%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 2
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Campylobacter gastroenteritis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Campylobacter infection
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Candida infection
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Cellulitis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral toxoplasmosis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Clostridium difficile infection
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cryptococcal meningoencephalitis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus chorioretinitis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Cytomegalovirus colitis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Cytomegalovirus gastritis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Cytomegalovirus hepatitis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Cytomegalovirus infection
         subjects affected / exposed
    11 / 109 (10.09%)
    16 / 108 (14.81%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    9 / 23
    13 / 23
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection reactivation
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Diarrhoea infectious
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    1 / 42 (2.38%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Infected lymphocele
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Infection
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    2 / 109 (1.83%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Oral candidiasis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parotitis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parvovirus B19 infection
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Pneumocystis jirovecii infection
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 109 (0.00%)
    3 / 108 (2.78%)
    0 / 70 (0.00%)
    2 / 42 (4.76%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia legionella
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Polyomavirus-associated nephropathy
         subjects affected / exposed
    5 / 109 (4.59%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    4 / 5
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostatitis Escherichia coli
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 109 (0.92%)
    2 / 108 (1.85%)
    2 / 70 (2.86%)
    1 / 42 (2.38%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    1 / 2
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal abscess
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    2 / 109 (1.83%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinitis
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Sepsis
         subjects affected / exposed
    1 / 109 (0.92%)
    2 / 108 (1.85%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Suspected COVID-19
         subjects affected / exposed
    1 / 109 (0.92%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Toxoplasmosis
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    6 / 109 (5.50%)
    5 / 108 (4.63%)
    5 / 70 (7.14%)
    1 / 42 (2.38%)
    6 / 73 (8.22%)
         occurrences causally related to treatment / all
    3 / 6
    1 / 11
    2 / 5
    0 / 1
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    2 / 109 (1.83%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 109 (0.92%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic complication
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Hypercalcaemia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Hypercreatininaemia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Hypervolaemia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    0 / 109 (0.00%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (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
    Hypoglycaemia
         subjects affected / exposed
    0 / 109 (0.00%)
    0 / 108 (0.00%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    		 De Novo Cohort: CFZ533 300 mg + MMF + CS De Novo Cohort: CFZ533 600 mg + MMF + CS Maintenance Cohort: CFZ533 450 mg + MMF +/- CS Maintenance Cohort: TAC + MMF +/- CS De Novo Cohort: TAC + MMF + CS
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    102 / 109 (93.58%)
    105 / 108 (97.22%)
    54 / 70 (77.14%)
    26 / 42 (61.90%)
    67 / 73 (91.78%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    3 / 109 (2.75%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    3
    1
    0
    0
    4
    Hypertension
         subjects affected / exposed
    29 / 109 (26.61%)
    36 / 108 (33.33%)
    12 / 70 (17.14%)
    1 / 42 (2.38%)
    15 / 73 (20.55%)
         occurrences all number
    36
    48
    14
    1
    15
    Hypotension
         subjects affected / exposed
    5 / 109 (4.59%)
    12 / 108 (11.11%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    5 / 73 (6.85%)
         occurrences all number
    5
    13
    1
    0
    6
    Lymphocele
         subjects affected / exposed
    7 / 109 (6.42%)
    4 / 108 (3.70%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences all number
    7
    4
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 109 (2.75%)
    2 / 108 (1.85%)
    4 / 70 (5.71%)
    1 / 42 (2.38%)
    1 / 73 (1.37%)
         occurrences all number
    3
    2
    4
    1
    1
    Fatigue
         subjects affected / exposed
    4 / 109 (3.67%)
    10 / 108 (9.26%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    2 / 73 (2.74%)
         occurrences all number
    4
    12
    0
    1
    2
    Oedema peripheral
         subjects affected / exposed
    13 / 109 (11.93%)
    21 / 108 (19.44%)
    4 / 70 (5.71%)
    1 / 42 (2.38%)
    7 / 73 (9.59%)
         occurrences all number
    18
    29
    4
    1
    9
    Pyrexia
         subjects affected / exposed
    17 / 109 (15.60%)
    20 / 108 (18.52%)
    7 / 70 (10.00%)
    4 / 42 (9.52%)
    4 / 73 (5.48%)
         occurrences all number
    18
    22
    9
    4
    5
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    7 / 109 (6.42%)
    11 / 108 (10.19%)
    6 / 70 (8.57%)
    2 / 42 (4.76%)
    2 / 73 (2.74%)
         occurrences all number
    8
    13
    10
    2
    2
    Dyspnoea
         subjects affected / exposed
    5 / 109 (4.59%)
    9 / 108 (8.33%)
    1 / 70 (1.43%)
    2 / 42 (4.76%)
    5 / 73 (6.85%)
         occurrences all number
    5
    11
    1
    2
    6
    Oropharyngeal pain
         subjects affected / exposed
    5 / 109 (4.59%)
    10 / 108 (9.26%)
    2 / 70 (2.86%)
    4 / 42 (9.52%)
    2 / 73 (2.74%)
         occurrences all number
    6
    10
    4
    4
    2
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    8 / 109 (7.34%)
    9 / 108 (8.33%)
    1 / 70 (1.43%)
    3 / 42 (7.14%)
    7 / 73 (9.59%)
         occurrences all number
    8
    14
    3
    3
    9
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    6 / 109 (5.50%)
    4 / 108 (3.70%)
    3 / 70 (4.29%)
    0 / 42 (0.00%)
    5 / 73 (6.85%)
         occurrences all number
    7
    4
    6
    0
    9
    Cytomegalovirus test positive
         subjects affected / exposed
    3 / 109 (2.75%)
    1 / 108 (0.93%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    3
    1
    1
    0
    5
    Lymphocyte count decreased
         subjects affected / exposed
    5 / 109 (4.59%)
    10 / 108 (9.26%)
    3 / 70 (4.29%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences all number
    6
    14
    4
    0
    2
    Neutrophil count decreased
         subjects affected / exposed
    5 / 109 (4.59%)
    13 / 108 (12.04%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    0 / 73 (0.00%)
         occurrences all number
    7
    23
    2
    0
    0
    SARS-CoV-2 test negative
         subjects affected / exposed
    6 / 109 (5.50%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    3 / 73 (4.11%)
         occurrences all number
    10
    1
    0
    0
    5
    Injury, poisoning and procedural complications
    Delayed graft function
         subjects affected / exposed
    8 / 109 (7.34%)
    7 / 108 (6.48%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences all number
    8
    7
    0
    0
    2
    Transplant dysfunction
         subjects affected / exposed
    4 / 109 (3.67%)
    8 / 108 (7.41%)
    1 / 70 (1.43%)
    1 / 42 (2.38%)
    0 / 73 (0.00%)
         occurrences all number
    5
    10
    1
    1
    0
    Procedural pain
         subjects affected / exposed
    19 / 109 (17.43%)
    13 / 108 (12.04%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    19
    15
    0
    0
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    3 / 109 (2.75%)
    3 / 108 (2.78%)
    1 / 70 (1.43%)
    3 / 42 (7.14%)
    2 / 73 (2.74%)
         occurrences all number
    3
    4
    1
    3
    2
    Tremor
         subjects affected / exposed
    5 / 109 (4.59%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    3 / 42 (7.14%)
    11 / 73 (15.07%)
         occurrences all number
    6
    2
    0
    4
    11
    Headache
         subjects affected / exposed
    11 / 109 (10.09%)
    15 / 108 (13.89%)
    6 / 70 (8.57%)
    4 / 42 (9.52%)
    8 / 73 (10.96%)
         occurrences all number
    18
    21
    7
    4
    10
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    23 / 109 (21.10%)
    36 / 108 (33.33%)
    4 / 70 (5.71%)
    3 / 42 (7.14%)
    12 / 73 (16.44%)
         occurrences all number
    27
    37
    4
    3
    13
    Leukocytosis
         subjects affected / exposed
    3 / 109 (2.75%)
    6 / 108 (5.56%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    3 / 73 (4.11%)
         occurrences all number
    3
    6
    0
    0
    3
    Leukopenia
         subjects affected / exposed
    31 / 109 (28.44%)
    31 / 108 (28.70%)
    9 / 70 (12.86%)
    1 / 42 (2.38%)
    16 / 73 (21.92%)
         occurrences all number
    40
    44
    11
    1
    16
    Lymphopenia
         subjects affected / exposed
    16 / 109 (14.68%)
    14 / 108 (12.96%)
    3 / 70 (4.29%)
    1 / 42 (2.38%)
    5 / 73 (6.85%)
         occurrences all number
    20
    17
    3
    1
    6
    Polycythaemia
         subjects affected / exposed
    1 / 109 (0.92%)
    2 / 108 (1.85%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    4 / 73 (5.48%)
         occurrences all number
    1
    2
    0
    1
    4
    Neutropenia
         subjects affected / exposed
    13 / 109 (11.93%)
    9 / 108 (8.33%)
    7 / 70 (10.00%)
    1 / 42 (2.38%)
    2 / 73 (2.74%)
         occurrences all number
    16
    9
    9
    1
    2
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    2 / 109 (1.83%)
    3 / 108 (2.78%)
    4 / 70 (5.71%)
    0 / 42 (0.00%)
    6 / 73 (8.22%)
         occurrences all number
    2
    3
    4
    0
    7
    Constipation
         subjects affected / exposed
    21 / 109 (19.27%)
    30 / 108 (27.78%)
    3 / 70 (4.29%)
    1 / 42 (2.38%)
    12 / 73 (16.44%)
         occurrences all number
    26
    41
    3
    1
    12
    Abdominal pain
         subjects affected / exposed
    10 / 109 (9.17%)
    8 / 108 (7.41%)
    4 / 70 (5.71%)
    3 / 42 (7.14%)
    5 / 73 (6.85%)
         occurrences all number
    12
    10
    4
    3
    7
    Diarrhoea
         subjects affected / exposed
    25 / 109 (22.94%)
    19 / 108 (17.59%)
    11 / 70 (15.71%)
    4 / 42 (9.52%)
    20 / 73 (27.40%)
         occurrences all number
    31
    26
    13
    5
    23
    Dyspepsia
         subjects affected / exposed
    2 / 109 (1.83%)
    4 / 108 (3.70%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    3
    5
    1
    0
    5
    Haemorrhoids
         subjects affected / exposed
    5 / 109 (4.59%)
    6 / 108 (5.56%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    6
    7
    1
    0
    4
    Nausea
         subjects affected / exposed
    13 / 109 (11.93%)
    13 / 108 (12.04%)
    0 / 70 (0.00%)
    4 / 42 (9.52%)
    11 / 73 (15.07%)
         occurrences all number
    17
    13
    0
    4
    12
    Vomiting
         subjects affected / exposed
    10 / 109 (9.17%)
    12 / 108 (11.11%)
    1 / 70 (1.43%)
    3 / 42 (7.14%)
    7 / 73 (9.59%)
         occurrences all number
    10
    12
    2
    3
    7
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 109 (0.92%)
    6 / 108 (5.56%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences all number
    1
    8
    1
    0
    1
    Rash
         subjects affected / exposed
    2 / 109 (1.83%)
    6 / 108 (5.56%)
    2 / 70 (2.86%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences all number
    2
    8
    2
    0
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    11 / 109 (10.09%)
    3 / 108 (2.78%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    8 / 73 (10.96%)
         occurrences all number
    11
    4
    0
    1
    8
    Haematuria
         subjects affected / exposed
    7 / 109 (6.42%)
    5 / 108 (4.63%)
    1 / 70 (1.43%)
    1 / 42 (2.38%)
    5 / 73 (6.85%)
         occurrences all number
    7
    6
    1
    1
    5
    Perinephric collection
         subjects affected / exposed
    2 / 109 (1.83%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    2
    1
    0
    0
    4
    Proteinuria
         subjects affected / exposed
    7 / 109 (6.42%)
    6 / 108 (5.56%)
    6 / 70 (8.57%)
    1 / 42 (2.38%)
    1 / 73 (1.37%)
         occurrences all number
    7
    6
    6
    2
    1
    Renal impairment
         subjects affected / exposed
    6 / 109 (5.50%)
    3 / 108 (2.78%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences all number
    6
    3
    0
    0
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    6 / 109 (5.50%)
    6 / 108 (5.56%)
    3 / 70 (4.29%)
    3 / 42 (7.14%)
    2 / 73 (2.74%)
         occurrences all number
    7
    6
    6
    3
    2
    Back pain
         subjects affected / exposed
    2 / 109 (1.83%)
    5 / 108 (4.63%)
    3 / 70 (4.29%)
    1 / 42 (2.38%)
    4 / 73 (5.48%)
         occurrences all number
    3
    5
    3
    1
    5
    Groin pain
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    5 / 73 (6.85%)
         occurrences all number
    1
    1
    0
    0
    5
    Pain in extremity
         subjects affected / exposed
    1 / 109 (0.92%)
    3 / 108 (2.78%)
    2 / 70 (2.86%)
    3 / 42 (7.14%)
    2 / 73 (2.74%)
         occurrences all number
    1
    3
    2
    3
    2
    Infections and infestations
    BK virus infection
         subjects affected / exposed
    11 / 109 (10.09%)
    13 / 108 (12.04%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    9 / 73 (12.33%)
         occurrences all number
    11
    14
    1
    0
    9
    Bronchitis
         subjects affected / exposed
    4 / 109 (3.67%)
    7 / 108 (6.48%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    2 / 73 (2.74%)
         occurrences all number
    6
    11
    0
    1
    2
    COVID-19
         subjects affected / exposed
    6 / 109 (5.50%)
    9 / 108 (8.33%)
    2 / 70 (2.86%)
    4 / 42 (9.52%)
    7 / 73 (9.59%)
         occurrences all number
    7
    10
    2
    4
    7
    Herpes zoster
         subjects affected / exposed
    2 / 109 (1.83%)
    4 / 108 (3.70%)
    3 / 70 (4.29%)
    0 / 42 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    2
    6
    3
    0
    4
    Cytomegalovirus infection
         subjects affected / exposed
    8 / 109 (7.34%)
    15 / 108 (13.89%)
    2 / 70 (2.86%)
    1 / 42 (2.38%)
    8 / 73 (10.96%)
         occurrences all number
    14
    19
    2
    1
    13
    Gastroenteritis
         subjects affected / exposed
    1 / 109 (0.92%)
    3 / 108 (2.78%)
    4 / 70 (5.71%)
    0 / 42 (0.00%)
    3 / 73 (4.11%)
         occurrences all number
    1
    3
    5
    0
    3
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 109 (5.50%)
    8 / 108 (7.41%)
    2 / 70 (2.86%)
    1 / 42 (2.38%)
    2 / 73 (2.74%)
         occurrences all number
    11
    8
    2
    2
    2
    Oral herpes
         subjects affected / exposed
    1 / 109 (0.92%)
    7 / 108 (6.48%)
    4 / 70 (5.71%)
    2 / 42 (4.76%)
    1 / 73 (1.37%)
         occurrences all number
    1
    12
    6
    2
    1
    Nasopharyngitis
         subjects affected / exposed
    6 / 109 (5.50%)
    8 / 108 (7.41%)
    5 / 70 (7.14%)
    2 / 42 (4.76%)
    2 / 73 (2.74%)
         occurrences all number
    10
    11
    6
    2
    2
    Urinary tract infection
         subjects affected / exposed
    27 / 109 (24.77%)
    19 / 108 (17.59%)
    5 / 70 (7.14%)
    2 / 42 (4.76%)
    17 / 73 (23.29%)
         occurrences all number
    39
    27
    8
    4
    30
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    3 / 109 (2.75%)
    6 / 108 (5.56%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences all number
    3
    6
    1
    0
    2
    Dyslipidaemia
         subjects affected / exposed
    4 / 109 (3.67%)
    1 / 108 (0.93%)
    2 / 70 (2.86%)
    0 / 42 (0.00%)
    5 / 73 (6.85%)
         occurrences all number
    5
    1
    2
    0
    5
    Gout
         subjects affected / exposed
    1 / 109 (0.92%)
    1 / 108 (0.93%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    1
    1
    0
    0
    9
    Hypercalcaemia
         subjects affected / exposed
    7 / 109 (6.42%)
    5 / 108 (4.63%)
    1 / 70 (1.43%)
    2 / 42 (4.76%)
    2 / 73 (2.74%)
         occurrences all number
    8
    5
    1
    2
    2
    Hyperkalaemia
         subjects affected / exposed
    8 / 109 (7.34%)
    18 / 108 (16.67%)
    1 / 70 (1.43%)
    1 / 42 (2.38%)
    18 / 73 (24.66%)
         occurrences all number
    8
    19
    1
    1
    18
    Hyperglycaemia
         subjects affected / exposed
    16 / 109 (14.68%)
    12 / 108 (11.11%)
    1 / 70 (1.43%)
    1 / 42 (2.38%)
    17 / 73 (23.29%)
         occurrences all number
    18
    13
    1
    1
    18
    Hypervolaemia
         subjects affected / exposed
    3 / 109 (2.75%)
    6 / 108 (5.56%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences all number
    3
    6
    0
    0
    2
    Hypocalcaemia
         subjects affected / exposed
    7 / 109 (6.42%)
    5 / 108 (4.63%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    10 / 73 (13.70%)
         occurrences all number
    10
    5
    0
    1
    10
    Hypokalaemia
         subjects affected / exposed
    13 / 109 (11.93%)
    21 / 108 (19.44%)
    1 / 70 (1.43%)
    1 / 42 (2.38%)
    3 / 73 (4.11%)
         occurrences all number
    13
    23
    1
    1
    3
    Hypophosphataemia
         subjects affected / exposed
    14 / 109 (12.84%)
    12 / 108 (11.11%)
    3 / 70 (4.29%)
    0 / 42 (0.00%)
    7 / 73 (9.59%)
         occurrences all number
    15
    12
    3
    0
    8
    Hypomagnesaemia
         subjects affected / exposed
    3 / 109 (2.75%)
    7 / 108 (6.48%)
    0 / 70 (0.00%)
    1 / 42 (2.38%)
    4 / 73 (5.48%)
         occurrences all number
    3
    8
    0
    1
    4
    Hypovolaemia
         subjects affected / exposed
    3 / 109 (2.75%)
    4 / 108 (3.70%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    4 / 73 (5.48%)
         occurrences all number
    3
    4
    0
    0
    5
    Iron deficiency
         subjects affected / exposed
    7 / 109 (6.42%)
    1 / 108 (0.93%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences all number
    7
    1
    1
    0
    2
    Metabolic acidosis
         subjects affected / exposed
    7 / 109 (6.42%)
    5 / 108 (4.63%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    6 / 73 (8.22%)
         occurrences all number
    7
    6
    0
    0
    6
    Steroid diabetes
         subjects affected / exposed
    7 / 109 (6.42%)
    9 / 108 (8.33%)
    0 / 70 (0.00%)
    0 / 42 (0.00%)
    2 / 73 (2.74%)
         occurrences all number
    7
    10
    0
    0
    2
    Vitamin D deficiency
         subjects affected / exposed
    2 / 109 (1.83%)
    6 / 108 (5.56%)
    1 / 70 (1.43%)
    0 / 42 (0.00%)
    1 / 73 (1.37%)
         occurrences all number
    2
    6
    1
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 May 2019
    This amendment extended the study by 48 months to 60 months. Kidney biopsies at Baseline and at Month 12 were made mandatory in both Cohort 1 and 2 which were to be sent to the central blinded reader for assessment
    10 Dec 2019
    This amendment introduced changes related to objectives and sample size.
    15 Dec 2020
    The key purpose of the amendment was to allow potential adaptations to study visits and study drug shipments during the COVID-19 pandemic.
    18 Mar 2021
    The primary purpose of this amendment was to incorporate feedback from the US Food and Drug Administration (FDA) on objectives.

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.nov for complete trial results.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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