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    Clinical Trial Results:
    Evaluation of Acute Rejection Rates in de novo Renal Transplant Recipients Following Thymoglobulin Induction, CNI-free, Nulojix (belatacept) -based Immunosuppression

    Summary
    EudraCT number
    		 2013-002090-21
    Trial protocol
    		 DE   AT  
    Global end of trial date
    05 Feb 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Sep 2021
    First version publication date
    16 Sep 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    IM103-177
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussee de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    Bristol-Myers Squibb International Corporation, Eu Study Start-Up Unit, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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
    30 Jul 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Feb 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to assess the incidence of clinically-suspected and biopsy proven acute rejection (CSBPAR) at 6 months post-transplant in de novo renal allograft recipients treated with thymoglobulin induction, rapid corticosteroid withdrawal, and maintenance belatacept in combination with EVL, or maintenance TAC in combination with MMF.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 May 2014
    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: 11
    Country: Number of subjects enrolled
    United States: 56
    Country: Number of subjects enrolled
    Germany: 1
    Worldwide total number of subjects
    68
    EEA total number of subjects
    1
    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)
    59
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 58 participants randomized and treated

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Treatment A
    Arm description
    		 BELA + EVL
    Arm type
    		 Experimental

    Investigational medicinal product name
    Belatacept
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    250mg IV

    Investigational medicinal product name
    Everolimus
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Chewable/dispersible tablet
    Routes of administration
    Buccal use
    Dosage and administration details
    0.25mg and 0.75mg

    Investigational medicinal product name
    Thymoglobulin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1.5 mg/kg IV

    Arm title
    		 Treatment B
    Arm description
    		 TAC + MMF
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tacrolimus
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Chewable/dispersible tablet
    Routes of administration
    Buccal use
    Dosage and administration details
    0.5mg and 1.0mg tablet

    Investigational medicinal product name
    Thymoglobulin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1.5 mg/kg IV

    Investigational medicinal product name
    Mycophenolate Mofetil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Chewable/dispersible tablet
    Routes of administration
    Buccal use
    Dosage and administration details
    0.5g to 2.0g

    Number of subjects in period 1 [1]
    		Treatment A Treatment B
    Started
    26
    32
    Completed
    23
    26
    Not completed
    3
    6
         Withdrew Consent
    1
    1
         Adverse event, non-fatal
    2
    2
         Discontinued Study Treatment
    -
    3
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Treatment Error resulted in participant flow error

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment A
    Reporting group description
    		 BELA + EVL

    Reporting group title
    Treatment B
    Reporting group description
    		 TAC + MMF

    Reporting group values
    		 Treatment A Treatment B Total
    Number of subjects
    		 26 32 58
    Age Categorical
    Units: Participants
        < 65
    		 22 28 50
        ≥ 65
    		 4 4 8
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 51.7 ± 12.8 50.8 ± 10.9 -
    Sex: Female, Male
    Units: Participants
        Female
    		 5 9 14
        Male
    		 21 23 44
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 0 3 3
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 3 6 9
        White
    		 23 21 44
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 0 2 2

    End points

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    End points reporting groups
    Reporting group title
    Treatment A
    Reporting group description
    		 BELA + EVL

    Reporting group title
    Treatment B
    Reporting group description
    		 TAC + MMF

    Subject analysis set title
    As Treated treatment A
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Due to treatment error, one participant from treatment A was treated in Treatment B

    Subject analysis set title
    As Treated Treatment B
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Due to treatment error, one participant from treatment A was treated in Treatment B

    Primary: Percentage of Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6 Months

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    End point title
    		 Percentage of Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6 Months [1]
    End point description
    Number of Participants with Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6 Months
    End point type
    Primary
    End point timeframe
    6 Months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This Endpoint does not have a statistical analysis
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: Percentage of participants
        number (confidence interval 95%)
    7.7 (0.9 to 25.1)
    9.4 (2.0 to 25.0)
    No statistical analyses for this end point

    Secondary: Time to Clinically-suspected biopsy-proven acute rejection (CSBPAR).

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    End point title
    		 Time to Clinically-suspected biopsy-proven acute rejection (CSBPAR).
    End point description
    Time to Clinically suspected biopsy proven acute rejection Here 9999 means NA
    End point type
    Secondary
    End point timeframe
    Up to 24 Months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    3
    3
    Units: Months
        arithmetic mean (full range (min-max))
    9999 (-9999 to 9999)
    9999 (-9999 to 9999)
    No statistical analyses for this end point

    Secondary: Treatment differences in Therapeutic Modalities

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    End point title
    		 Treatment differences in Therapeutic Modalities
    End point description
    Treatment Received for Biopsy Proven Acute Rejection (Banff Grade IA or Higher), or Humoral (Antibody Mediated) Rejection Treatment regimen: Categorical analysis of CSBPAR episodes by treatment received.
    End point type
    Secondary
    End point timeframe
    at 6, 12 and 24 Months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: Percentage of participants with CSBPARs
    number (not applicable)
        Corticosteroids (6 months)
    7.7
    9.4
        Lymphocyte depleting agent (6 months)
    0
    6.3
        Plasmapheresis (6 months)
    0
    0
        IVIG (6 months)
    0
    3.1
        Rituximab (6 months)
    0
    0
        Corticosteroids (12 months)
    15.4
    12.5
        Lymphocyte depleting agent (12 months)
    3.8
    6.3
        Plasmapheresis (12 months)
    0
    0
        IVIG (12 months)
    0
    3.1
        Rituximab (12 months)
    0
    0
        Corticosteroids (24 months)
    19.2
    12.5
        Lymphocyte depleting agent (24 months)
    3.8
    6.3
        Plasmapheresis (24 months)
    0
    0
        IVIG (24 months)
    0
    3.1
        Rituximab (24 months)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants who survive with a functioning graft

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    End point title
    		 Number of Participants who survive with a functioning graft
    End point description
    Number of all participants who survive with a functioning graft at 6, 12 and 24 months post transplant
    End point type
    Secondary
    End point timeframe
    At 6, 12 and 24 months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: Participants
        At 6 Months
    25
    31
        At 12 Months
    25
    31
        At 24 Months
    25
    31
    No statistical analyses for this end point

    Secondary: Number of Participants deaths post transplant

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    End point title
    		 Number of Participants deaths post transplant
    End point description
    Number of participant deaths at 6, 12 and 24 months post transplant
    End point type
    Secondary
    End point timeframe
    up to 24 months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: Participants
        At 6 Months
    0
    0
        At 12 Months
    0
    0
        At 24 Months
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants who experience graft loss post transplant

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    End point title
    		 Number of Participants who experience graft loss post transplant
    End point description
    Number of all participants who experience graft loss at 6, 12 and 24 months post transplant
    End point type
    Secondary
    End point timeframe
    At 6, 12 and 24 months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: Participants
        At 6 Months
    1
    1
        At 12 Months
    1
    1
        At 24 Months
    1
    1
    No statistical analyses for this end point

    Secondary: Time to Event: Graft Loss and death

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    End point title
    		 Time to Event: Graft Loss and death
    End point description
    The Number of days to participant Graft Loss and death for any reason
    End point type
    Secondary
    End point timeframe
    Up to 728 Days
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    1
    1
    Units: Days
        Graft Loss
    107
    2
        Death
    0
    0
    No statistical analyses for this end point

    Secondary: Absolute calculated Glomerular Filtration Rate (cGFR): Mean

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    End point title
    		 Absolute calculated Glomerular Filtration Rate (cGFR): Mean
    End point description
    Absolute (mean and median) cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula
    End point type
    Secondary
    End point timeframe
    Up 24 Months post-transplant
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mL/min/1.73 m^2
    arithmetic mean (confidence interval 95%)
        At 3 Months
    69.2 (60.2 to 78.3)
    62.2 (55.3 to 69.1)
        At 6 Months
    66.0 (55.8 to 76.2)
    63.9 (56.2 to 71.5)
        At 12 Months
    66.2 (56.9 to 75.4)
    62.0 (53.4 to 70.6)
        At 24 Months
    71.8 (62.5 to 81.0)
    68.7 (59.2 to 78.2)
    No statistical analyses for this end point

    Secondary: Median calculated Glomerular Filtration Rate (cGFR)

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    End point title
    		 Median calculated Glomerular Filtration Rate (cGFR)
    End point description
    Median cGFR values at 3, 6, 12 and 24 months post-transplant, as determined from the 4-variable Modification of Diet in Renal Disease (MDRD) formula
    End point type
    Secondary
    End point timeframe
    Up 24 Months post-transplant
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mL/min/1.73 m^2
    median (full range (min-max))
        At 3 Months
    64.0 (52.0 to 80.0)
    62.0 (55.0 to 79.0)
        At 6 Months
    64.0 (56.0 to 79.0)
    67.0 (55.0 to 75.0)
        At 12 Months
    66.0 (58.0 to 77.0)
    62.5 (47.5 to 74.0)
        At 24 Months
    73.5 (59.5 to 84.5)
    68.0 (56.0 to 82.0)
    No statistical analyses for this end point

    Secondary: Mean Change from Month 3 in cGFR

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    End point title
    		 Mean Change from Month 3 in cGFR
    End point description
    The mean change from Month 3 cGFR at 3, 6, 12 and 24 months post-transplant
    End point type
    Secondary
    End point timeframe
    Up 24 Months post-transplant
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mL/min/1.73 m^2
    arithmetic mean (confidence interval 95%)
        At 3 Months
    0 (0 to 0)
    0 (0 to 0)
        At 6 Months
    -3.2 (-10.9 to 4.5)
    2.8 (-0.2 to 5.8)
        At 12 Months
    -3.1 (-12.6 to 6.5)
    1.4 (-3.3 to 6.0)
        At 24 Months
    1.8 (-8.6 to 12.3)
    6.7 (1.6 to 11.8)
    No statistical analyses for this end point

    Secondary: Urine Protein Creatinine Ratio (UPr/Cr)

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    End point title
    		 Urine Protein Creatinine Ratio (UPr/Cr)
    End point description
    Urine protein to creatinine ratio (UPr/Cr) at 3, 6, 12 and 24 months post-transplant.
    End point type
    Secondary
    End point timeframe
    Up 24 Months post-transplant
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mg Protein/mg Creatinine
    arithmetic mean (confidence interval 95%)
        At 3 Months
    0.3146 (0.1985 to 0.4307)
    0.1412 (0.1097 to 0.1726)
        At 6 Months
    0.3896 (0.2326 to 0.5466)
    0.1461 (0.1203 to 0.1720)
        At 12 Months
    0.2835 (0.1648 to 0.4021)
    0.1849 (0.1041 to 0.2658)
        At 24 Months
    0.3940 (0.2199 to 0.5680)
    0.1685 (0.1174 to 0.2195)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Donor Specific Anti-HLA Antibodies (DSA)

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    End point title
    		 Percentage of Participants with Donor Specific Anti-HLA Antibodies (DSA)
    End point description
    Percentage of participants with, and titers of pre-existing (pre-transplant) DSA on Day 1 (pre-transplant, pre-dose), and at Months 12 and 24 posttransplant
    End point type
    Secondary
    End point timeframe
    Up to 24 Months
    End point values
    		 Treatment A Treatment B As Treated treatment A As Treated Treatment B
    Number of subjects analysed
    0 [2]
    0 [3]
    25
    33
    Units: Percentage of Participants
    number (not applicable)
        Baseline Class 1 DSA
    10
    0
        Baseline Class 2 DSA
    0
    0
        Baseline Both Class 1 and 2 DSA
    0
    0
        12 Month Class 1 DSA
    8
    0
        12 Month Class 2 DSA
    0
    3.03
        12 Month Both Class 1 and 2 DSA
    0
    0
        24 Month Class 1 DSA
    8
    3.03
        24 Month Class 2 DSA
    0
    3.03
        24 Month Both Class 1 and 2 DSA
    0
    0
    Notes
    [2] - This is for the ITT population
    [3] - This is for the ITT Population
    No statistical analyses for this end point

    Secondary: Percentage of Participants with De Novo Donor Specific Anti-HLA Antibodies (DSA)

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    End point title
    		 Percentage of Participants with De Novo Donor Specific Anti-HLA Antibodies (DSA)
    End point description
    Characterization of any de novo DSA detected by IgM and IgG subclasses, and by the presence or absence of complement fixing properties.
    End point type
    Secondary
    End point timeframe
    Up to 24 Months
    End point values
    		 Treatment A Treatment B As Treated treatment A As Treated Treatment B
    Number of subjects analysed
    0 [4]
    0 [5]
    25
    33
    Units: Percentage
    number (not applicable)
        Baseline Class 1 DSA
    10
    0
        Baseline Class 2 DSA
    0
    0
        Baseline Both Class 1 and 2 DSA
    0
    0
        De Novo 12 Month Class 1 DSA
    0
    0
        De Novo 12 Month Class 2 DSA
    0
    0
        De Novo 12 Month Both Class 1 and 2 DSA
    0
    0
        De Novo 24 Month Class 1 DSA
    0
    3.03
        De Novo 24 Month Class 2 DSA
    0
    0
        De Novo 24 Month Both Class 1 and 2 DSA
    0
    0
    Notes
    [4] - This is for the ITT population
    [5] - This is for the ITT population
    No statistical analyses for this end point

    Secondary: Percentage of participants with Adverse Events (AEs)

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    End point title
    		 Percentage of participants with Adverse Events (AEs)
    End point description
    Percentage of participants with AEs up to 24 months post-transplant
    End point type
    Secondary
    End point timeframe
    Up to 24 months Post-Transplant
    End point values
    		 Treatment A Treatment B As Treated treatment A As Treated Treatment B
    Number of subjects analysed
    0 [6]
    0 [7]
    25
    33
    Units: Percentage of participants with AEs
        number (not applicable)
    100.0
    97.0
    Notes
    [6] - This is for the As treated population
    [7] - This is for the As treated population
    No statistical analyses for this end point

    Secondary: Percentage of participants with Serious Adverse Events (SAEs)

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    End point title
    		 Percentage of participants with Serious Adverse Events (SAEs)
    End point description
    Percentage of participants with SAEs up to 24 months post-transplant
    End point type
    Secondary
    End point timeframe
    Up to 24 months Post-Transplant
    End point values
    		 Treatment A Treatment B As Treated treatment A As Treated Treatment B
    Number of subjects analysed
    0 [8]
    0 [9]
    25
    33
    Units: Percentage of participants with SAEs
        number (not applicable)
    52.0
    60.6
    Notes
    [8] - This is for the As treated population
    [9] - This is for the As treated population
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Events of Special Interest (ESIs)

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    End point title
    		 Percentage of Participants with Events of Special Interest (ESIs)
    End point description
    Percentage of participants which have one of the following events of special interest: Serious Infections Post-Transplant Lymphoproliferative Disorder (PTLD) Progressive multifocal leukoencephalopathy (PML) Malignancies (Other than PTLD) including non-melanoma skin carcinomas (Malignancies) Tuberculosis Infections Central Nervous System (CNS) Infections Viral Infections Infusion Related reactions within 24 hours since belatacept infusion
    End point type
    Secondary
    End point timeframe
    Up to 24 Months
    End point values
    		 Treatment A Treatment B As Treated treatment A As Treated Treatment B
    Number of subjects analysed
    0 [10]
    0 [11]
    25
    33
    Units: Percentage of participants with ESIs
    number (not applicable)
        Serious Infections
    16.0
    15.2
        PTLD
    4.0
    3.0
        PML
    0
    0
        Malignancies
    4.0
    3.0
        TB
    0
    0
        CNS Infections
    0
    0
        Viral Infections
    0
    0
        Infusion Related Reactions
    1.0
    0
    Notes
    [10] - This is for the ITT population
    [11] - This is for the ITT population
    No statistical analyses for this end point

    Secondary: Mean and Mean change from baseline in blood glucose

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    End point title
    		 Mean and Mean change from baseline in blood glucose
    End point description
    Mean fasting blood glucose levels, and mean changes from baseline values at Months 6, 12 and 24 months post- transplant
    End point type
    Secondary
    End point timeframe
    Up to 24 months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mg/dL
    arithmetic mean (confidence interval 95%)
        Mean Value at 6 months
    107.2 (86.6 to 127.8)
    107.2 (93.8 to 120.7)
        Change from baseline at 6 months
    4.9 (-5.8 to 15.7)
    4.8 (-17.6 to 27.2)
        Mean Value at 12 months
    101.1 (85.3 to 117.0)
    127.5 (99.2 to 155.8)
        Change from baseline at 12 months
    -1.3 (-24.7 to 22.1)
    20.6 (0.4 to 40.8)
        Mean Value at 24 months
    127.5 (93.7 to 161.4)
    111.8 (87.1 to 136.5)
        Change from baseline at 24 months
    22.3 (-15.7 to 60.3)
    15.0 (-3.2 to 33.2)
    No statistical analyses for this end point

    Secondary: Mean and Mean change from baseline in whole blood HbA1c

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    End point title
    		 Mean and Mean change from baseline in whole blood HbA1c
    End point description
    Mean whole blood HbA1C concentrations, and mean changes from baseline values at Months 6, 12 and 24 months post-transplant.
    End point type
    Secondary
    End point timeframe
    Up to 24 months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mg/dL
    arithmetic mean (confidence interval 95%)
        Mean Value at 6 months
    6.11 (5.47 to 6.75)
    6.13 (5.44 to 6.82)
        Change from baseline at 6 months
    0.34 (0.06 to 0.62)
    0.48 (0.04 to 0.91)
        Mean Value at 12 months
    6.18 (5.42 to 6.93)
    6.21 (5.50 to 6.92)
        Change from baseline at 12 months
    0.47 (-0.00 to 0.95)
    0.32 (-0.17 to 0.81)
        Mean Value at 24 months
    6.24 (5.27 to 7.20)
    6.29 (5.38 to 7.20)
        Change from baseline at 24 months
    0.66 (-0.05 to 1.37)
    0.41 (-0.13 to 0.95)
    No statistical analyses for this end point

    Secondary: Percentage of participants with New onset diabetes after transplant

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    End point title
    		 Percentage of participants with New onset diabetes after transplant
    End point description
    Percentage of participants with New Onset Diabetes After Transplantation (NODAT) at 6, 12, and 24 months post-transplant.
    End point type
    Secondary
    End point timeframe
    up to 24 months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: Percentage of participants
    number (confidence interval 95%)
        Up to 6 Months
    11.5 (2.4 to 30.2)
    6.3 (0.8 to 20.8)
        Up to 12 Months
    11.5 (2.4 to 30.2)
    6.3 (0.8 to 20.8)
        Up to 24 Months
    15.4 (4.4 to 34.9)
    12.5 (3.5 to 29.0)
    No statistical analyses for this end point

    Secondary: Absolute Values of Blood Pressure: Mean

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    End point title
    		 Absolute Values of Blood Pressure: Mean
    End point description
    Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;
    End point type
    Secondary
    End point timeframe
    Up to 24 Months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mmHg
    arithmetic mean (confidence interval 95%)
        Diastolic Month 3
    78.7 (74.2 to 83.2)
    77.7 (74.0 to 81.3)
        Systolic Month 3
    134.2 (126.9 to 141.6)
    131.0 (124.9 to 137.0)
        Diastolic Month 6
    77.4 (73.6 to 81.3)
    79.4 (76.0 to 82.9)
        Systolic Month 6
    128.1 (121.8 to 134.5)
    133.0 (127.2 to 138.8)
        Diastolic Month 12
    78.7 (74.6 to 82.9)
    80.1 (76.4 to 83.8)
        Systolic Month 12
    131.0 (125.6 to 136.4)
    131.0 (123.4 to 138.7)
        Diastolic Month 24
    78.1 (74.2 to 81.9)
    78.5 (74.3 to 82.8)
        Systolic Month 24
    130.9 (125.2 to 136.5)
    131.7 (125.2 to 138.2)
    No statistical analyses for this end point

    Secondary: Absolute Values of Blood Pressure: Median

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    End point title
    		 Absolute Values of Blood Pressure: Median
    End point description
    Absolute (mean and median) values for SBP and DBP at 3, 6, 12 and 24 months posttransplant;
    End point type
    Secondary
    End point timeframe
    Up to 24 Months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mmHg
    median (full range (min-max))
        Diastolic Month 3
    78.5 (70.0 to 88.0)
    80.0 (70.0 to 84.0)
        Systolic Month 3
    135.5 (127.0 to 144.0)
    131.0 (122.0 to 138.0)
        Diastolic Month 6
    75.5 (70.5 to 83.0)
    80.0 (71.0 to 85.5)
        Systolic Month 6
    127.0 (114.5 to 136.5)
    131.0 (124.0 to 142.5)
        Diastolic Month 12
    77.0 (71.5 to 86.0)
    81.0 (72.0 to 88.0)
        Systolic Month 12
    130.0 (119.0 to 142.0)
    126.0 (115.0 to 146.0)
        Diastolic Month 24
    78.0 (71.0 to 86.0)
    79.0 (69.5 to 85.0)
        Systolic Month 24
    130.0 (122.0 to 142.0)
    130.0 (121.5 to 139.0)
    No statistical analyses for this end point

    Secondary: Mean changes from baseline values for Blood Pressure

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    End point title
    		 Mean changes from baseline values for Blood Pressure
    End point description
    Mean changes from baseline values for SBP and DBP at 6, 12 and 24 months post-transplant
    End point type
    Secondary
    End point timeframe
    Up to 24 Months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mmHg
    arithmetic mean (confidence interval 95%)
        Diastolic Month 6
    1.0 (-4.7 to 6.7)
    4.8 (-1.2 to 10.8)
        Systolic Month 6
    -4.0 (-13.9 to 5.9)
    -0.7 (-10.0 to 8.7)
        Diastolic Month 12
    2.3 (-4.0 to 8.6)
    5.4 (-1.0 to 11.7)
        Systolic Month 12
    -1.1 (-9.6 to 7.4)
    -3.2 (-14.7 to 8.3)
        Diastolic Month 24
    0.9 (-5.5 to 7.3)
    2.1 (-3.9 to 8.1)
        Systolic Month 24
    -2.3 (-12.2 to 7.6)
    -4.2 (-14.4 to 6.0)
    No statistical analyses for this end point

    Secondary: Absolute Values of Fasting Lipid Values: Mean

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    End point title
    		 Absolute Values of Fasting Lipid Values: Mean
    End point description
    Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant for the following: Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)
    End point type
    Secondary
    End point timeframe
    Up to 24 Months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mg/dL
    arithmetic mean (confidence interval 95%)
        TC Month 3
    181.2 (157.8 to 204.7)
    174.4 (154.8 to 194.1)
        TC Month 6
    197.7 (177.9 to 217.4)
    175 (158.8 to 191.6)
        TC Month 12
    189.0 (171.7 to 206.3)
    169.9 (153.8 to 186.0)
        TC Month 24
    193.2 (172.1 to 214.2)
    168.2 (152.9 to 183.4)
        HDL Month 3
    50.6 (43.5 to 57.6)
    50.4 (43.9 to 56.9)
        HDL Month 6
    46.4 (41.3 to 51.5)
    53.9 (45.9 to 61.8)
        HDL Month 12
    49.4 (44.0 to 54.8)
    49.6 (42.5 to 56.6)
        HDL Month 24
    50.1 (44.7 to 55.5)
    51.3 (43.0 to 59.6)
        LDL Month 3
    96.9 (77.9 to 115.9)
    96.5 (80.3 to 112.6)
        LDL Month 6
    115.2 (98.1 to 132.3)
    93.7 (79.2 to 108.2)
        LDL Month 12
    107.5 (92.8 to 122.2)
    88.0 (74.3 to 101.8)
        LDL Month 24
    97.9 (81.6 to 114.2)
    91.5 (75.4 to 107.6)
        TG Month 3
    171.6 (118.1 to 225.0)
    137.8 (106.6 to 168.9)
        TG Month 6
    180.0 (140.2 to 219.7)
    138.3 (108.0 to 168.5)
        TG Month 12
    162.4 (132.2 to 192.6)
    161.3 (126.4 to 196.1)
        TG Month 24
    263.4 (131.2 to 395.5)
    145.0 (99.8 to 190.2)
    No statistical analyses for this end point

    Secondary: Absolute Values of Fasting Lipid Values: Median

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    End point title
    		 Absolute Values of Fasting Lipid Values: Median
    End point description
    Absolute (mean and median) values at 3, 6, 12 and 24 months post-transplant for the following: Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)
    End point type
    Secondary
    End point timeframe
    Up to 24 Months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mg/dL
    median (full range (min-max))
        TC Month 3
    167.0 (160.0 to 213.0)
    173.0 (146.0 to 197.0)
        TC Month 6
    187.0 (170.5 to 226.5)
    178.0 (146.0 to 199.0)
        TC Month 12
    184.0 (166.0 to 213.0)
    171.5 (146.5 to 193.5)
        TC Month 24
    193.0 (166.0 to 206.0)
    166.0 (137.0 to 201.0)
        HDL Month 3
    45.0 (39.0 to 62.0)
    49.0 (38.0 to 63.0)
        HDL Month 6
    45.5 (39.0 to 51.0)
    49.0 (37.0 to 68.0)
        HDL Month 12
    50.0 (40.0 to 58.0)
    47.0 (37.0 to 61.0)
        HDL Month 24
    49.0 (43.0 to 58.0)
    49.0 (35.0 to 71.0)
        LDL Month 3
    89.0 (74.0 to 127.0)
    95.0 (75.0 to 116.0)
        LDL Month 6
    99.5 (85.5 to 143.0)
    100.0 (66.0 to 115.0)
        LDL Month 12
    104.0 (85.0 to 128.0)
    91.5 (65.0 to 109.0)
        LDL Month 24
    103.5 (74.0 to 121.0)
    86.0 (70.0 to 119.0)
        TG Month 3
    147.0 (107.0 to 195.0)
    128.0 (81.0 to 174.0)
        TG Month 6
    157.5 (113.5 to 245.5)
    126.0 (85.0 to 194.0)
        TG Month 12
    154.0 (100.0 to 230.0)
    130.0 (106.0 to 202.0)
        TG Month 24
    159.0 (137.0 to 284.0)
    114.0 (80.0 to 174.0)
    No statistical analyses for this end point

    Secondary: Mean changes from baseline values of Lipid values

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    End point title
    		 Mean changes from baseline values of Lipid values
    End point description
    Mean changes from baseline values in the following: Serum total cholesterol (TC) Serum high density lipoprotein (HDL) cholesterol Serum low density lipoprotein (LDL) cholesterol Serum triglycerides (TG)
    End point type
    Secondary
    End point timeframe
    at months 12 and 24
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: mg/dL
    arithmetic mean (confidence interval 95%)
        TC Month 12
    25.7 (3.5 to 47.9)
    -2.8 (-41.5 to 35.8)
        TC Month 24
    26.6 (4.0 to 49.1)
    10.0 (-9.9 to 29.9)
        HDL Month 12
    5.4 (-0.3 to 11.0)
    1.9 (-3.7 to 7.5)
        HDL Month 24
    6.2 (0.7 to 11.6)
    4.8 (-2.2 to 11.9)
        LDL Month 12
    25.7 (7.9 to 43.4)
    10.8 (-10.8 to 32.4)
        LDL Month 24
    17.4 (0.0 to 34.7)
    15.7 (-4.4 to 35.7)
        TG Month 12
    3.3 (-26.0 to 32.5)
    -86.1 (-288.9 to 116.7)
        TG Month 24
    106.8 (-32.6 to 246.2)
    -13.6 (-73.8 to 46.5)
    No statistical analyses for this end point

    Secondary: Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6, 12 and 24 Months

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    End point title
    		 Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6, 12 and 24 Months
    End point description
    Clinically-suspected biopsy-proven acute rejection (CSBPAR) at 6, 12 and 24 Months Change in the incidence of CSBPAR at 6, 12 and 24 months post transplant, in the belatacept + EVL(Treatment A) as compared to TAC + MMF (Treatment B).
    End point type
    Secondary
    End point timeframe
    Up to 24 Months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: Percentage of CSBPAR
    number (confidence interval 95%)
        CSBPAR at 6 Months
    7.7 (0.9 to 25.1)
    9.4 (2.0 to 25.0)
        CSBPAR at 12 months
    11.5 (2.4 to 30.2)
    12.5 (3.5 to 29.0)
        CSBPAR at 24 Months
    15.4 (4.4 to 34.9)
    12.5 (3.5 to 29.0)
    Statistical analysis title
    		 Statistical Analysis of CSBAR at 6 months
    Statistical analysis description
    Change in Incidence of Treatment A as compared to Treatment B at 6 Months
    Comparison groups
    Treatment A v Treatment B
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Incidence of Change
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.9
         upper limit
    		 16.7
    Statistical analysis title
    		 Statistical Analysis of CSBAR at 12 months
    Statistical analysis description
    Change in Incidence of Treatment A as compared to Treatment B at 12 Months
    Comparison groups
    Treatment A v Treatment B
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Incidence of Change
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.2
         upper limit
    		 18.9
    Statistical analysis title
    		 Statistical Analysis of CSBAR at 24 months
    Statistical analysis description
    Change in Incidence of Treatment A as compared to Treatment B at 24 Months
    Comparison groups
    Treatment A v Treatment B
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Incidence of Change
    Point estimate
    2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.1
         upper limit
    		 23.9

    Secondary: Percentage of participants with BANFF Grade by severity grades. BANFF Type (Grade) for Acute/Active Rejection

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    End point title
    		 Percentage of participants with BANFF Grade by severity grades. BANFF Type (Grade) for Acute/Active Rejection
    End point description
    Treatment differences in the severity grades to treat all episodes of CSBPAR at 6, 12, and 24 months post-transplant. Type 1A - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>4 mononuclear cells/Tubular cross section or group of 10 Tubular cell). Type 1B - Cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>10 mononuclear cells/Tubular cross section or group of 10 Tubular cell).Type 2A - Cases with mild to moderate intimal arteritis.Type 2B - Cases with severe intimal arteritis comprising >25% of the luminal area. Type 3 - Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (v3 with accompanying lymphocytic inflammation)
    End point type
    Secondary
    End point timeframe
    At 6, 12 and 24 Months
    End point values
    		 Treatment A Treatment B
    Number of subjects analysed
    26
    32
    Units: Percentage of Participants
    number (not applicable)
        6 Months: Mild Acute (1A)
    3.8
    0
        6 Months: Mild Acute (1B)
    0
    3.1
        6 Months: Moderate Acute (2A)
    7.7
    6.3
        6 Months: Moderate Acute (2B)
    0
    0
        6 Months: Severe Acute
    0
    0
        12 Months: Mild Acute (1A)
    7.7
    3.1
        12 Months: Mild Acute (1B)
    0
    3.1
        12 Months: Moderate Acute (2A)
    7.7
    6.3
        12 Months: Moderate Acute (2B)
    0
    0
        12 Months: Severe Acute
    0
    0
        24 Months: Mild Acute (1A)
    11.5
    3.1
        24 Months: Mild Acute (1B)
    0
    3.1
        24 Months: Moderate Acute (2A)
    7.7
    6.3
        24 Months: Moderate Acute (2B)
    0
    0
        24 Months: Severe Acute
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of particpants with laboratory test abnormalities (LTAs)

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    End point title
    		 Percentage of particpants with laboratory test abnormalities (LTAs)
    End point description
    Percentage of participants with laboratory tests with marked laboratory abnormalities
    End point type
    Secondary
    End point timeframe
    At 24 Months
    End point values
    		 Treatment A Treatment B As Treated treatment A As Treated Treatment B
    Number of subjects analysed
    0 [12]
    0 [13]
    25
    33
    Units: Percentage of participants
    number (not applicable)
        Hemoglobin (Low)
    12.0
    6.1
        Leukocytes (low)
    0
    3.0
        Lymphocyte (Absolute) (low)
    84.0
    69.7
        Neutrophils (Absolute) (low)
    0
    3.0
        Aspartate Aminotransferase (High)
    4.0
    0
        Creatinine (High)
    16.0
    3.0
        Inorganic Phosphorus (low)
    24.0
    12.1
        Potassium (high)
    4.0
    0
        Sodium (low)
    4.0
    0
        Albumin (low)
    0
    3.0
        Glucose (high)
    8.0
    12.1
        Triglycerides (high)
    12.0
    0
        Uric Acid (high)
    8.0
    0
    Notes
    [12] - This is for the As Treated Population
    [13] - This is for the As Treated population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs collected were reported between first dose upto 56 days after last dose of study treatment.
    Adverse event reporting additional description
    Because 1 participant ith BPAR had been randomized to the BELA+EVL group, but had then mistakenly been treated with TAC+MMF beginning on Day 1 and continuing through the entire 2-year study period, analysis was also performed using the modified ITT (as-treated) population, in which the participant was analyzed as having received TAC+MMF.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Thymoglobulin + Tacrolimus + Mycophenolate Mofetil
    Reporting group description
    		 Subjects were administered thymoglobulin 1.5 mg/kg intravenously (IV) on day 1 (Day of transplant) and daily thereafter (or less frequently, as tolerated) for a total cumulative dose between 3.0 and 5.5 mg/kg plus Tacrolimus total initial dose of 0.1 mg/kg/day orally in 2 divided doses and adjusted thereafter on the basis of therapeutic drug monitoring, to target pre-dose blood concentrations of 4-11 ng/mL. plus Mycophenolate Mofetil 0.5-2.0 gram (g) per day (0.25 to 1.0 g bid) and up to 3.0 g per day administered orally or IV until the remainder of the study (24 months).

    Reporting group title
    Thymoglobulin + Belatacept + Everolimus
    Reporting group description
    		 Subjects were administered thymoglobulin 1.5 milligram (mg)/kg intravenously (IV) on day 1 (Day of transplant) and daily thereafter (or less frequently, as tolerated) for a total cumulative dose between 3.0 and 5.5 mg/kg plus Belatacept 10 mg/kg IV on days (1, 5, 14, 29, 43, 57, 71, 84), 5 mg/kg IV every 4 Weeks plus Everolimus 3.0 mg/day (1.5 mg bid) orally starting on Day 3, Dosing was adjusted to keep pre-dose levels at 6 to 10 nanogram (ng)/mL for the initial 3 months post-transplantation and at 4 to 8 ng/mL after 3 months until the remainder of the study (24 months).

    Serious adverse events
    		 Thymoglobulin + Tacrolimus + Mycophenolate Mofetil Thymoglobulin + Belatacept + Everolimus
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 33 (60.61%)
    13 / 25 (52.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Plasma cell myeloma
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post transplant lymphoproliferative disorder
         subjects affected / exposed
    1 / 33 (3.03%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Dry gangrene
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Renal transplant failure
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    3 / 33 (9.09%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Arteriospasm coronary
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 33 (3.03%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Central nervous system vasculitis
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar ataxia
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 33 (3.03%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    4 / 33 (12.12%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal fluid collection
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal haematoma
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haemorrhage
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder stenosis
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy toxic
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perinephric collection
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal artery stenosis
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    1 / 33 (3.03%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteral necrosis
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis acute
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal graft infection
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 33 (0.00%)
    3 / 25 (12.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Thymoglobulin + Tacrolimus + Mycophenolate Mofetil Thymoglobulin + Belatacept + Everolimus
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    30 / 33 (90.91%)
    25 / 25 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Hypertension
         subjects affected / exposed
    8 / 33 (24.24%)
    6 / 25 (24.00%)
         occurrences all number
    8
    6
    Orthostatic hypotension
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    3
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Fatigue
         subjects affected / exposed
    3 / 33 (9.09%)
    4 / 25 (16.00%)
         occurrences all number
    3
    7
    Oedema peripheral
         subjects affected / exposed
    5 / 33 (15.15%)
    5 / 25 (20.00%)
         occurrences all number
    6
    7
    Pyrexia
         subjects affected / exposed
    3 / 33 (9.09%)
    2 / 25 (8.00%)
         occurrences all number
    3
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 33 (6.06%)
    2 / 25 (8.00%)
         occurrences all number
    3
    3
    Dyspnoea
         subjects affected / exposed
    2 / 33 (6.06%)
    2 / 25 (8.00%)
         occurrences all number
    2
    4
    Epistaxis
         subjects affected / exposed
    0 / 33 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    3
    Nasal congestion
         subjects affected / exposed
    2 / 33 (6.06%)
    2 / 25 (8.00%)
         occurrences all number
    2
    2
    Oropharyngeal pain
         subjects affected / exposed
    5 / 33 (15.15%)
    1 / 25 (4.00%)
         occurrences all number
    5
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    5 / 33 (15.15%)
    3 / 25 (12.00%)
         occurrences all number
    5
    3
    Anxiety
         subjects affected / exposed
    1 / 33 (3.03%)
    2 / 25 (8.00%)
         occurrences all number
    1
    2
    Investigations
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Blood bicarbonate decreased
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Blood creatinine increased
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Donor specific antibody present
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    3
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    3
    Lymphocyte count decreased
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 33 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    3
    Injury, poisoning and procedural complications
    Complications of transplanted kidney
         subjects affected / exposed
    1 / 33 (3.03%)
    2 / 25 (8.00%)
         occurrences all number
    1
    2
    Fall
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Graft complication
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Incision site pain
         subjects affected / exposed
    3 / 33 (9.09%)
    0 / 25 (0.00%)
         occurrences all number
    4
    0
    Procedural pain
         subjects affected / exposed
    4 / 33 (12.12%)
    4 / 25 (16.00%)
         occurrences all number
    4
    4
    Limb injury
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Wound
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 33 (3.03%)
    4 / 25 (16.00%)
         occurrences all number
    1
    4
    Palpitations
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Tachycardia
         subjects affected / exposed
    2 / 33 (6.06%)
    2 / 25 (8.00%)
         occurrences all number
    2
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    4 / 33 (12.12%)
    2 / 25 (8.00%)
         occurrences all number
    4
    3
    Paraesthesia
         subjects affected / exposed
    3 / 33 (9.09%)
    0 / 25 (0.00%)
         occurrences all number
    3
    0
    Hypoaesthesia
         subjects affected / exposed
    3 / 33 (9.09%)
    1 / 25 (4.00%)
         occurrences all number
    3
    1
    Headache
         subjects affected / exposed
    7 / 33 (21.21%)
    5 / 25 (20.00%)
         occurrences all number
    7
    6
    Tremor
         subjects affected / exposed
    6 / 33 (18.18%)
    0 / 25 (0.00%)
         occurrences all number
    6
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 33 (15.15%)
    4 / 25 (16.00%)
         occurrences all number
    6
    5
    Leukocytosis
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Leukopenia
         subjects affected / exposed
    7 / 33 (21.21%)
    8 / 25 (32.00%)
         occurrences all number
    9
    9
    Neutropenia
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Thrombocytopenia
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    3
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    4 / 33 (12.12%)
    0 / 25 (0.00%)
         occurrences all number
    5
    0
    Abdominal pain
         subjects affected / exposed
    3 / 33 (9.09%)
    2 / 25 (8.00%)
         occurrences all number
    3
    2
    Abdominal pain lower
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 25 (4.00%)
         occurrences all number
    4
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 33 (3.03%)
    2 / 25 (8.00%)
         occurrences all number
    1
    2
    Aphthous ulcer
         subjects affected / exposed
    2 / 33 (6.06%)
    4 / 25 (16.00%)
         occurrences all number
    2
    8
    Constipation
         subjects affected / exposed
    10 / 33 (30.30%)
    5 / 25 (20.00%)
         occurrences all number
    12
    6
    Diarrhoea
         subjects affected / exposed
    10 / 33 (30.30%)
    4 / 25 (16.00%)
         occurrences all number
    14
    4
    Dyspepsia
         subjects affected / exposed
    4 / 33 (12.12%)
    0 / 25 (0.00%)
         occurrences all number
    5
    0
    Flatulence
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    5 / 33 (15.15%)
    0 / 25 (0.00%)
         occurrences all number
    6
    0
    Mouth ulceration
         subjects affected / exposed
    0 / 33 (0.00%)
    10 / 25 (40.00%)
         occurrences all number
    0
    18
    Nausea
         subjects affected / exposed
    13 / 33 (39.39%)
    5 / 25 (20.00%)
         occurrences all number
    19
    5
    Vomiting
         subjects affected / exposed
    7 / 33 (21.21%)
    5 / 25 (20.00%)
         occurrences all number
    12
    5
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Seborrhoeic dermatitis
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    4 / 33 (12.12%)
    3 / 25 (12.00%)
         occurrences all number
    4
    3
    Haematuria
         subjects affected / exposed
    5 / 33 (15.15%)
    1 / 25 (4.00%)
         occurrences all number
    6
    1
    Perinephric collection
         subjects affected / exposed
    4 / 33 (12.12%)
    0 / 25 (0.00%)
         occurrences all number
    4
    0
    Renal tubular necrosis
         subjects affected / exposed
    3 / 33 (9.09%)
    1 / 25 (4.00%)
         occurrences all number
    3
    1
    Renal impairment
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Proteinuria
         subjects affected / exposed
    2 / 33 (6.06%)
    4 / 25 (16.00%)
         occurrences all number
    2
    5
    Urinary retention
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 33 (3.03%)
    6 / 25 (24.00%)
         occurrences all number
    1
    6
    Back pain
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Flank pain
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Myalgia
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Muscle spasms
         subjects affected / exposed
    3 / 33 (9.09%)
    0 / 25 (0.00%)
         occurrences all number
    3
    0
    Pain in extremity
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Infections and infestations
    BK virus infection
         subjects affected / exposed
    3 / 33 (9.09%)
    4 / 25 (16.00%)
         occurrences all number
    3
    4
    Body tinea
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Bronchitis
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Cytomegalovirus viraemia
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    3
    0
    Fungal infection
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Influenza
         subjects affected / exposed
    3 / 33 (9.09%)
    1 / 25 (4.00%)
         occurrences all number
    3
    1
    Nasopharyngitis
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 25 (4.00%)
         occurrences all number
    2
    1
    Onychomycosis
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 33 (6.06%)
    2 / 25 (8.00%)
         occurrences all number
    4
    2
    Tooth infection
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Urinary tract infection
         subjects affected / exposed
    4 / 33 (12.12%)
    5 / 25 (20.00%)
         occurrences all number
    11
    7
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 33 (6.06%)
    2 / 25 (8.00%)
         occurrences all number
    2
    2
    Diabetes mellitus
         subjects affected / exposed
    5 / 33 (15.15%)
    2 / 25 (8.00%)
         occurrences all number
    5
    2
    Fluid overload
         subjects affected / exposed
    1 / 33 (3.03%)
    3 / 25 (12.00%)
         occurrences all number
    1
    5
    Hyperglycaemia
         subjects affected / exposed
    5 / 33 (15.15%)
    3 / 25 (12.00%)
         occurrences all number
    6
    3
    Hyperkalaemia
         subjects affected / exposed
    11 / 33 (33.33%)
    1 / 25 (4.00%)
         occurrences all number
    12
    1
    Hypocalcaemia
         subjects affected / exposed
    3 / 33 (9.09%)
    2 / 25 (8.00%)
         occurrences all number
    3
    2
    Hypoglycaemia
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    3
    0
    Hypokalaemia
         subjects affected / exposed
    3 / 33 (9.09%)
    7 / 25 (28.00%)
         occurrences all number
    3
    10
    Hyponatraemia
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Hypomagnesaemia
         subjects affected / exposed
    8 / 33 (24.24%)
    2 / 25 (8.00%)
         occurrences all number
    9
    5
    Hypophosphataemia
         subjects affected / exposed
    8 / 33 (24.24%)
    9 / 25 (36.00%)
         occurrences all number
    8
    12
    Metabolic acidosis
         subjects affected / exposed
    3 / 33 (9.09%)
    4 / 25 (16.00%)
         occurrences all number
    4
    4
    Vitamin D deficiency
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Oct 2013
    Modifications were made to the WOCBP definition, including FSH requirements and HRT washout period to align with BMS standards. Exclusion criteria were updated to remove annual mammogram, WOCBP criteria that do not apply. Updates to The Time & Events Table include removal of the Annual Mammogram to allow Investigators to use standard of care practices, the addition of a Neurological Exam and clarifications to align the table with the protocol text and with BMS belatacept program clinical studies. Protocol was updated with Neurological Exam requirements, modification of the clinical criteria and monitoring of PTLD. Modifications were made to the Events of Special Interest. Inclusion of Data Monitoring Committee. Minor edits and clarifications.
    23 Dec 2014
    Modification of the study design, including the addition of an accepted standard of care active comparator treatment group and a change in the immunosuppressive medications paradigm. Updates to the research hypothesis and study objectives. Revisions to eligibility criteria. Addition of text for pregnancy precautions and U.S. reporting requirements from the CellCept Risk Evaluation and Mitigation Strategy. Clarification of the timing of randomization in relation to transplant surgery and initial dose of study drugs, and the temporal sequence of study drug dosing. Updates to the Time & Events Table including the addition of collection of safety and biomarker specimens; and clarifications to align the tables with the protocol text and other studies within belatacept clinical study program. Update the requirements for evaluation of renal biopsy specimens to include assessments for acute antibody-mediated and as T-cell mediated rejection. Updates to the primary and secondary endpoints and statistical section to support the revised study design and to eliminate the allowance of crossover subjects. Minor edits and clarifications, including section numbering
    25 Aug 2015
    Modification of the study design to remove an experimental treatment group: Thymoglobulin + belatacept + mycophenolate mofetil with rapid corticosteroid withdrawal, from the study design to eliminate a potentially higher risk of acute rejection. Updates to the randomization ratio, sample size per treatment group and sample size statistical determinations. Syntactical edits and clarifications to support the revised study design.
    19 Jan 2016
    Clarification of antiviral prophylaxis requirement. Updates treatment and rescreening of living donor patients with a positive IGRA at screening. Revise protocol with recent administrative changes.
    11 Nov 2016
    Decrease number of sites and subjects. Statistical Sample Size Considerations updated. Clarification that all grades of acute rejection, will be included in analyses of the primary and relevant secondary endpoints.
    14 Aug 2017
    Clarify timing of collection of belatacept and comparator blood levels for clinically suspected AR, PML or PTLD. Update Procedural Outline Tables 5.1-2 and 5.1-3 to allow for collection of a blood sample for determination of the belatacept or comparator blood level at the time of any clinically suspected episode of acute rejection, PML or PTLD. Provide guidance regarding the evaluation and acceptable range for oral immunosuppressive treatment compliance. The type of T-cell responses to be tested for in cases of clinically suspected PTLD or PML was clarified as being “anti-viral”, rather than specifically “anti-EBV” in nature. Made modifications to secondary and exploratory endpoints to align the analyses of acute rejection with the statistical analysis plan, and corrected minor formatting and typographical errors throughout the protocol.

    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.
    One participant with BPAR had been randomized to the BELA+EVL group, but had then mistakenly been treated with TAC+MMF beginning on Day 1 and continuing through the entire 2-year study period. Due to this, therefore inaccurate data is not presented.
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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