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    Clinical Trial Results:
    A double-blind, randomised, placebo-controlled trial evaluating the effect of BI 655064 administered as subcutaneous injections, on renal response after one year of treatment, in patients with active lupus nephritis

    Summary
    EudraCT number
    		 2015-001750-15
    Trial protocol
    		 ES   CZ   GR   DE   PL   AT   PT   GB   FR   IT  
    Global end of trial date
    18 Aug 2020

    Results information
    Results version number
    		 v1
    This version publication date
    04 Jul 2021
    First version publication date
    04 Jul 2021
    Other versions
    		 v2

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    1293.10
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02770170
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Boehringer Ingelheim
    Sponsor organisation address
    Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
    Public contact
    Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com
    Scientific contact
    Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.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
    15 Oct 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Jun 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Aug 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objectives were to characterise the dose-response relationship, identify the target dose for Phase III development, and investigate the safety and efficacy of 3 doses of BI 655064 administered subcutaneously for 52 weeks as add-on therapy to standard of care treatment in patients with active lupus nephritis.
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all patients as required.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Aug 2016
    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
    Australia: 2
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Czechia: 6
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    Germany: 11
    Country: Number of subjects enrolled
    Greece: 9
    Country: Number of subjects enrolled
    Hong Kong: 4
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    Japan: 15
    Country: Number of subjects enrolled
    Malaysia: 3
    Country: Number of subjects enrolled
    Mexico: 22
    Country: Number of subjects enrolled
    Philippines: 28
    Country: Number of subjects enrolled
    Poland: 16
    Country: Number of subjects enrolled
    Portugal: 7
    Country: Number of subjects enrolled
    Serbia: 7
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    Thailand: 26
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 31
    Country: Number of subjects enrolled
    Korea, Republic of: 3
    Worldwide total number of subjects
    209
    EEA total number of subjects
    62
    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)
    207
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This is a double-blind, randomised, placebo-controlled trial evaluating the effect of BI 655064 administered as subcutaneous injections, on renal response after one year of treatment, in patients with active lupus nephritis.

    Pre-assignment
    Screening details
    		 All patients were screened for eligibility prior to participation in the trial. Patients attended a specialist site which ensured that they (the patients) strictly met all inclusion and none of the exclusion criteria. Patients were not to be allocated to a treatment group if any of the entry criteria were violated.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    Double-blind

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 120 mg BI 655064
    Arm description
    		 Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BI 655064
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.

    Arm title
    		 180 mg BI 655064
    Arm description
    		 Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BI 655064
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.

    Arm title
    		 240 mg BI 655064
    Arm description
    		 Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    BI 655064
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.

    Arm title
    		 Placebo
    Arm description
    		 Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.
    Arm type
    		 Placebo

    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
    Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.

    Number of subjects in period 1 [1]
    		120 mg BI 655064 180 mg BI 655064 240 mg BI 655064 Placebo
    Started
    21
    20
    40
    40
    Completed
    14
    17
    35
    33
    Not completed
    7
    3
    5
    7
         Consent withdrawn by subject
    -
    -
    -
    2
         Adverse event, non-fatal
    4
    3
    5
    3
         due to disease worsening
    -
    -
    -
    1
         due to pregnancy
    1
    -
    -
    -
         Lack of efficacy
    2
    -
    -
    1
    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: Worldwide 209 patients were enrolled in this trial, whereof 121 actually participated.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    120 mg BI 655064
    Reporting group description
    		 Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.

    Reporting group title
    180 mg BI 655064
    Reporting group description
    		 Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.

    Reporting group title
    240 mg BI 655064
    Reporting group description
    		 Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.

    Reporting group values
    		 120 mg BI 655064 180 mg BI 655064 240 mg BI 655064 Placebo Total
    Number of subjects
    		 21 20 40 40 121
    Age categorical
    Treated set (TS): This patient set included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 21 20 40 40 121
        From 65-84 years
    		 0 0 0 0 0
        85 years and over
    		 0 0 0 0 0
    Age Continuous
    Treated set (TS): This patient set included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
    Units: years
        arithmetic mean (standard deviation)
    		 35.9 ( 11.4 ) 34.5 ( 9.9 ) 34.3 ( 10.3 ) 33.9 ( 9.8 ) -
    Sex: Female, Male
    Treated set (TS): This patient set included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
    Units: Participants
        Female
    		 16 18 36 38 108
        Male
    		 5 2 4 2 13
    Ethnicity (NIH/OMB)
    Treated set (TS): This patient set included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
    Units: Subjects
        Hispanic or Latino
    		 5 4 8 7 24
        Not Hispanic or Latino
    		 16 16 32 33 97
        Unknown or Not Reported
    		 0 0 0 0 0
    Race (NIH/OMB)
    Treated set (TS): This patient set included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 9 9 17 17 52
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 1 0 2 1 4
        White
    		 9 11 21 22 63
        More than one race
    		 1 0 0 0 1
        Unknown or Not Reported
    		 1 0 0 0 1
    estimated glomerular filtration rate (eGFR) at baseline
    estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Treated set (TS): This patient set included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
    Units: milliLitres /minute /1.73 squaremeter
        arithmetic mean (standard deviation)
    		 85.857 ( 34.268 ) 99.850 ( 21.109 ) 91.125 ( 32.673 ) 88.775 ( 29.914 ) -

    End points

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    End points reporting groups
    Reporting group title
    120 mg BI 655064
    Reporting group description
    		 Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.

    Reporting group title
    180 mg BI 655064
    Reporting group description
    		 Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.

    Reporting group title
    240 mg BI 655064
    Reporting group description
    		 Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.

    Subject analysis set title
    120 mg BI 655064
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.

    Subject analysis set title
    180 mg BI 655064
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.

    Subject analysis set title
    240 mg BI 655064
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.

    Primary: Percentage of patients with complete renal response (CRR) at week 52

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    End point title
    		 Percentage of patients with complete renal response (CRR) at week 52
    End point description
    Complete renal response (CRR) was defined as urine protein (UP) < 0.5 g/day at Week 52 and either estimated glomerular filtration rate (eGFR) within normal range at Week 52 or decrease in eGFR < 20% from baseline at Week 52 if eGFR was below normal range (below lower limit of normal [LLN], where LLN = 90 mL/min). CRR at Week 52 (derived using UP from the 24 h urine collections) was analyzed using a logistic regression model. Factors in the model included treatment and the covariates race (Asian/Non-Asian) and proteinuria at screening (UP/urine creatinine (UC) <3 or >=3 g/day). Pairwise comparisons of the modelled proportions of patients with CRR at each dose level to placebo were performed. Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.
    End point type
    Primary
    End point timeframe
    At week 52.
    End point values
    		 120 mg BI 655064 180 mg BI 655064 240 mg BI 655064 Placebo
    Number of subjects analysed
    21
    20
    40
    40
    Units: Percentage of Participants
        number (not applicable)
    38.32
    44.95
    44.56
    48.33
    Statistical analysis title
    		 MCPMod quadratic model fit
    Statistical analysis description
    Multiple comparison procedures and modelling (MCPmod) techniques for logistic regression was used.
    Comparison groups
    120 mg BI 655064 v 180 mg BI 655064 v 240 mg BI 655064 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7271 [1]
    Method
    		 MCPMod quadratic model fit
    Confidence interval
    Notes
    [1] - An alpha of 0.20 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
    Statistical analysis title
    		 MCPMod sigmoidal Emax model fit
    Statistical analysis description
    Multiple comparison procedures and modelling (MCPmod) techniques for logistic regression was used.
    Comparison groups
    120 mg BI 655064 v 180 mg BI 655064 v 240 mg BI 655064 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6415 [2]
    Method
    		 MCPMod sigmoidal Emax model fit
    Confidence interval
    Notes
    [2] - An alpha of 0.20 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
    Statistical analysis title
    		 MCPMod Emax model fit
    Statistical analysis description
    Multiple comparison procedures and modelling (MCPmod) techniques for logistic regression was used.
    Comparison groups
    120 mg BI 655064 v 180 mg BI 655064 v 240 mg BI 655064 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7367 [3]
    Method
    		 MCPMod Emax model fit
    Confidence interval
    Notes
    [3] - An alpha of 0.20 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
    Statistical analysis title
    		 MCPMod exponential model fit
    Statistical analysis description
    Multiple comparison procedures and modelling (MCPmod) techniques for logistic regression was used.
    Comparison groups
    120 mg BI 655064 v 180 mg BI 655064 v 240 mg BI 655064 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6624 [4]
    Method
    		 MCPMod exponential model fit
    Confidence interval
    Notes
    [4] - An alpha of 0.20 was used for one-sided test. The MCPMod procedure adjusts for multiplicity.
    Statistical analysis title
    		 Logistic regression
    Statistical analysis description
    include treatment and covariates, race (Asian or non−Asian), proteinuria at screening (<3g/day or >= 3g/day) Confidence intervals calculated using delta method
    Comparison groups
    120 mg BI 655064 v Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4645
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -10
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -27.292
         upper limit
    		 7.288
    Statistical analysis title
    		 Logistic regression
    Statistical analysis description
    include treatment and covariates, race (Asian or non−Asian), proteinuria at screening (<3g/day or >= 3g/day) Confidence intervals calculated using delta method
    Comparison groups
    180 mg BI 655064 v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8084
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -3.38
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -21.204
         upper limit
    		 14.451
    Statistical analysis title
    		 Logistic regression
    Statistical analysis description
    include treatment and covariates, race (Asian or non−Asian), proteinuria at screening (<3g/day or >= 3g/day) Confidence intervals calculated using delta method
    Comparison groups
    240 mg BI 655064 v Placebo
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7398
    Method
    		 Regression, Logistic
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -3.77
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -18.364
         upper limit
    		 10.832

    Secondary: Percentage of patients with complete renal response (CRR) at week 26

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    End point title
    		 Percentage of patients with complete renal response (CRR) at week 26
    End point description
    Complete renal response (CRR) was defined as urine protein (UP) < 0.5 g/day at Week 26 and either estimated glomerular filtration rate (eGFR) within normal range at Week 26 or decrease in eGFR < 20% from baseline at Week 26 if eGFR was below normal range (below lower limit of normal [LLN], where LLN = 90 mL/min). Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.
    End point type
    Secondary
    End point timeframe
    At week 26.
    End point values
    		 120 mg BI 655064 180 mg BI 655064 240 mg BI 655064 Placebo
    Number of subjects analysed
    21
    20
    40
    40
    Units: Percentage of Participants
        number (not applicable)
    28.6
    50.0
    35.0
    37.5
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    120 mg BI 655064 v Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5773
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -8.93
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -23.66
         upper limit
    		 7.64
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    180 mg BI 655064 v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4013
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    12.5
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -4.59
         upper limit
    		 29.03
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    240 mg BI 655064 v Placebo
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8965
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -2.5
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -15.98
         upper limit
    		 11.1

    Secondary: Percentage of patients with partial renal response (PRR) at week 26

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    End point title
    		 Percentage of patients with partial renal response (PRR) at week 26
    End point description
    Partial renal response (PRR) was defined as at least 50% reduction of proteinuria from baseline if estimated glomerular filtration rate (eGFR) was within normal range at time of assessment or decrease of eGFR <20% from baseline if eGFR was below normal range at time of assessment. Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.
    End point type
    Secondary
    End point timeframe
    At week 26.
    End point values
    		 120 mg BI 655064 180 mg BI 655064 240 mg BI 655064 Placebo
    Number of subjects analysed
    21
    20
    40
    40
    Units: Percentage of Participants
        number (not applicable)
    42.9
    75.0
    62.5
    62.5
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    120 mg BI 655064 v Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1476
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -19.64
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -35.38
         upper limit
    		 -2.48
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    180 mg BI 655064 v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4013
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    12.5
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -4.2
         upper limit
    		 26.86
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    240 mg BI 655064 v Placebo
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -13.63
         upper limit
    		 13.63

    Secondary: Percentage of patients with partial renal response (PRR) at week 52

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    End point title
    		 Percentage of patients with partial renal response (PRR) at week 52
    End point description
    Partial renal response (PRR) was defined as at least 50% reduction of proteinuria from baseline if estimated glomerular filtration rate (eGFR) was within normal range at time of assessment or decrease of eGFR <20% from baseline if eGFR was below normal range at time of assessment. Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.
    End point type
    Secondary
    End point timeframe
    At week 52.
    End point values
    		 120 mg BI 655064 180 mg BI 655064 240 mg BI 655064 Placebo
    Number of subjects analysed
    21
    20
    40
    40
    Units: Percentage of Participants
        number (not applicable)
    33.3
    65.0
    55.0
    60.0
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    120 mg BI 655064 v Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0512
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -26.67
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -41.52
         upper limit
    		 -9.42
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    180 mg BI 655064 v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7597
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    5
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -12.1
         upper limit
    		 20.74
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    240 mg BI 655064 v Placebo
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7505
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -5
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -18.74
         upper limit
    		 9.02

    Secondary: Percentage of patients with major renal response (MRR) at week 26

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    End point title
    		 Percentage of patients with major renal response (MRR) at week 26
    End point description
    Major renal response was defined as follows depending on proteinuria at baseline: -If baseline proteinuria was <3 g/day and patient had complete renal response (CRR) -If baseline proteinuria was >= 3 g/day and proteinuria < 1 g/day and either estimated glomerular filtration rate (eGFR) within normal range or decrease in eGFR <20% from baseline at Week 26 if eGFR was below normal range (below lower limit of normal (LLN), where LLN = 90 mL/min) Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.
    End point type
    Secondary
    End point timeframe
    At week 26.
    End point values
    		 120 mg BI 655064 180 mg BI 655064 240 mg BI 655064 Placebo
    Number of subjects analysed
    21
    20
    40
    40
    Units: Percentage of Participants
        number (not applicable)
    28.6
    55.0
    37.5
    50.0
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    120 mg BI 655064 v Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1269
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -21.43
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -36.03
         upper limit
    		 -4.41
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    240 mg BI 655064 v Placebo
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2906
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -12.5
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -25.99
         upper limit
    		 1.68
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    180 mg BI 655064 v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7889
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    5
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -12.24
         upper limit
    		 21.62

    Secondary: Percentage of patients with major renal response (MRR) at week 52

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    End point title
    		 Percentage of patients with major renal response (MRR) at week 52
    End point description
    Major renal response was defined as follows depending on proteinuria at baseline: -If baseline proteinuria was <3 g/day and patient had complete renal response (CRR) -If baseline proteinuria was >= 3 g/day and proteinuria < 1 g/day and either estimated glomerular filtration rate (eGFR) within normal range or decrease in eGFR <20% from baseline at Week 52 if eGFR was below normal range (below lower limit of normal (LLN), where LLN = 90 mL/min) Intent to treat (ITT) set: This patient set included all patients from the treated set who had a baseline (or screening) proteinuria (spot urine could be used if a patient did not have 24 h urine collections) and a baseline or screening estimated glomerular filtration rate (eGFR) value.
    End point type
    Secondary
    End point timeframe
    At week 52.
    End point values
    		 120 mg BI 655064 180 mg BI 655064 240 mg BI 655064 Placebo
    Number of subjects analysed
    21
    20
    40
    40
    Units: Percentage of Participants
        number (not applicable)
    42.9
    55.0
    52.5
    52.5
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    120 mg BI 655064 v Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5687
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -9.64
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -25.79
         upper limit
    		 7.45
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    180 mg BI 655064 v Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9217
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.5
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -14.67
         upper limit
    		 19.17
    Statistical analysis title
    		 Barnard test of association
    Statistical analysis description
    Unadjusted absolute risk difference; Confidence intervals calculated using Newcombe method
    Comparison groups
    240 mg BI 655064 v Placebo
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Barnard test of association
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -14.03
         upper limit
    		 14.03

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first does of study medication until end of the 52-week treatment + 8 weeks of follow-up, up to 60 weeks.
    Adverse event reporting additional description
    Treated set (TS): This patient set included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    120 mg BI 655064
    Reporting group description
    		 Participants in dose group 1 received two subcutaneous injections per week, one of 120 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064 alternating with placebo, up to 52 weeks.

    Reporting group title
    180 mg BI 655064
    Reporting group description
    		 Participants in dose group 2 received two subcutaneous injections per week, one of 180 milligrams (mg) of BI 655064 and one of matching placebo on the same day for 3 weeks followed by one subcutaneous injection per week of 180 mg of BI 655064 alternating with placebo, up to 52 weeks.

    Reporting group title
    240 mg BI 655064
    Reporting group description
    		 Participants in dose group 3 received two subcutaneous injections per week of 120 milligrams (mg) of BI 655064 (240 mg in total) on the same day for 3 weeks followed by one subcutaneous injection per week of 120 mg of BI 655064, up to 52 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants in the placebo group received two subcutaneous injections per week of placebo on the same day for 3 weeks followed by one subcutaneous injection per week of placebo, up to 52 weeks.

    Serious adverse events
    		 120 mg BI 655064 180 mg BI 655064 240 mg BI 655064 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 21 (28.57%)
    6 / 20 (30.00%)
    10 / 40 (25.00%)
    8 / 40 (20.00%)
         number of deaths (all causes)
    0
    0
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Foot fracture
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Ventricular tachycardia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Blood and lymphatic system disorders
    Agranulocytosis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 21 (4.76%)
    2 / 20 (10.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Chorioretinopathy
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulcerative keratitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal food impaction
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis chronic
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lupus nephritis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conjunctivitis viral
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital herpes simplex
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis cryptococcal
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    2 / 40 (5.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 120 mg BI 655064 180 mg BI 655064 240 mg BI 655064 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    17 / 21 (80.95%)
    13 / 20 (65.00%)
    34 / 40 (85.00%)
    35 / 40 (87.50%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    2 / 40 (5.00%)
    3 / 40 (7.50%)
         occurrences all number
    1
    1
    2
    3
    Hypotension
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 20 (10.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
         occurrences all number
    0
    3
    2
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
         occurrences all number
    3
    0
    1
    1
    Fatigue
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
         occurrences all number
    2
    1
    3
    1
    Injection site pain
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    3 / 40 (7.50%)
    0 / 40 (0.00%)
         occurrences all number
    2
    1
    3
    0
    Oedema peripheral
         subjects affected / exposed
    3 / 21 (14.29%)
    1 / 20 (5.00%)
    3 / 40 (7.50%)
    2 / 40 (5.00%)
         occurrences all number
    4
    1
    3
    2
    Pyrexia
         subjects affected / exposed
    3 / 21 (14.29%)
    0 / 20 (0.00%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
         occurrences all number
    4
    0
    2
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    5 / 40 (12.50%)
    1 / 40 (2.50%)
         occurrences all number
    1
    2
    5
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    3 / 40 (7.50%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    3
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 21 (4.76%)
    2 / 20 (10.00%)
    3 / 40 (7.50%)
    1 / 40 (2.50%)
         occurrences all number
    1
    3
    4
    1
    Investigations
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    3 / 40 (7.50%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    6
    0
    Weight increased
         subjects affected / exposed
    2 / 21 (9.52%)
    2 / 20 (10.00%)
    5 / 40 (12.50%)
    2 / 40 (5.00%)
         occurrences all number
    2
    2
    8
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 21 (4.76%)
    2 / 20 (10.00%)
    1 / 40 (2.50%)
    3 / 40 (7.50%)
         occurrences all number
    1
    2
    1
    3
    Headache
         subjects affected / exposed
    3 / 21 (14.29%)
    1 / 20 (5.00%)
    6 / 40 (15.00%)
    5 / 40 (12.50%)
         occurrences all number
    3
    1
    8
    6
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 21 (14.29%)
    0 / 20 (0.00%)
    3 / 40 (7.50%)
    1 / 40 (2.50%)
         occurrences all number
    3
    0
    6
    1
    Leukopenia
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    4 / 40 (10.00%)
    1 / 40 (2.50%)
         occurrences all number
    1
    0
    5
    3
    Lymphopenia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    5 / 40 (12.50%)
    1 / 40 (2.50%)
         occurrences all number
    0
    0
    6
    1
    Neutropenia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    6 / 40 (15.00%)
    1 / 40 (2.50%)
         occurrences all number
    0
    1
    11
    1
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    3 / 40 (7.50%)
         occurrences all number
    0
    0
    1
    3
    Vision blurred
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    5 / 21 (23.81%)
    3 / 20 (15.00%)
    9 / 40 (22.50%)
    6 / 40 (15.00%)
         occurrences all number
    6
    4
    9
    8
    Vomiting
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    2 / 40 (5.00%)
    3 / 40 (7.50%)
         occurrences all number
    1
    3
    2
    4
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    3 / 40 (7.50%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    4
    0
    Alopecia
         subjects affected / exposed
    0 / 21 (0.00%)
    3 / 20 (15.00%)
    9 / 40 (22.50%)
    7 / 40 (17.50%)
         occurrences all number
    0
    3
    9
    7
    Erythema
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    4 / 40 (10.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    0
    5
    3
    Rash
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    6 / 40 (15.00%)
    2 / 40 (5.00%)
         occurrences all number
    2
    0
    9
    2
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    1 / 21 (4.76%)
    3 / 20 (15.00%)
    2 / 40 (5.00%)
    2 / 40 (5.00%)
         occurrences all number
    1
    3
    2
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 21 (14.29%)
    0 / 20 (0.00%)
    4 / 40 (10.00%)
    6 / 40 (15.00%)
         occurrences all number
    3
    0
    5
    7
    Arthritis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    4 / 40 (10.00%)
    4 / 40 (10.00%)
         occurrences all number
    0
    1
    4
    4
    Muscle spasms
         subjects affected / exposed
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 40 (2.50%)
    3 / 40 (7.50%)
         occurrences all number
    1
    1
    1
    4
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    2 / 40 (5.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    0
    2
    3
    Gastroenteritis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    3 / 40 (7.50%)
    0 / 40 (0.00%)
         occurrences all number
    0
    1
    3
    0
    Herpes zoster
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    4 / 40 (10.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    1
    4
    3
    Nasopharyngitis
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    4 / 40 (10.00%)
    7 / 40 (17.50%)
         occurrences all number
    2
    1
    5
    10
    Oral candidiasis
         subjects affected / exposed
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    1 / 40 (2.50%)
         occurrences all number
    5
    1
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    3 / 40 (7.50%)
    3 / 40 (7.50%)
         occurrences all number
    0
    0
    4
    3
    Rhinitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    3 / 40 (7.50%)
    0 / 40 (0.00%)
         occurrences all number
    0
    0
    4
    0
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 21 (23.81%)
    6 / 20 (30.00%)
    7 / 40 (17.50%)
    8 / 40 (20.00%)
         occurrences all number
    6
    9
    8
    9
    Urinary tract infection
         subjects affected / exposed
    1 / 21 (4.76%)
    2 / 20 (10.00%)
    4 / 40 (10.00%)
    6 / 40 (15.00%)
         occurrences all number
    2
    3
    5
    6
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    1 / 40 (2.50%)
         occurrences all number
    2
    0
    1
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    2 / 40 (5.00%)
    5 / 40 (12.50%)
         occurrences all number
    0
    1
    2
    5

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Nov 2015
    Inclusion criterion 3 was revised to allow the inclusion of patients with a positive antidsDNA antibody at screening or around the time of start of induction therapy. Initially the patients had to have a positive anti-dsDNA antibody at screening. Exclusion criterion 9 (‘live vaccination within 6 weeks before randomisation’) was added.
    02 Feb 2016
    According to the updated SmPC for MMF, additional requirements for pregnancy tests and contraception methods, as well as recommendations regarding blood and semen donation were added in the respective sections of the CTP.
    24 Nov 2016
    Statements were included that vital status information was to be collected at Week 60 (EOS visit) for randomised patients who discontinued from the study before EOS. Inclusion criterion 1 was revised: Women of childbearing potential were to use '2 reliable methods of birth control, one of which should be highly effective’ instead of '2 highly effective methods of birth control’. Also, in the definition of ‘women of nonchildbearing potential’, ‘tubal occlusion’ was removed as a sterilisation method. In exclusion criterion 4, the definition of antiphospholipid syndrome was modified. This had been requested by authorities. The following AEs were defined as AESIs (in addition to ‘hepatic injury’): injection reactions including anaphylactic reaction, cytokine release syndrome, opportunistic infections and/or severe infections, lymphoproliferative disorders (e.g. B- and T-cell lymphoma, Non-Hodgkin lymphoma and Hodgkin lymphoma, hepatosplenic T-cell lymphoma), thrombosis and adjunct immunosuppression. Other additional changes have been applied.
    17 Feb 2017
    If a higher dose of i.v. steroids was considered necessary by the investigator, a total dose of up to 3 g was acceptable for initial induction treatment.
    06 Oct 2017
    Proteinuria at screening <3 g/day or ≥3 g/day was also defined as UP/UC <3 or UP/UC ≥3. Inclusion criterion 3 was modified: one of the documented criteria for SLE had to be a positive anti-dsDNA antibody or a positive antinuclear antibody. The following exclusion criterion was deleted: ‘acute presence of oliguria (<500 mL/day)’. Further instructions with regard to steroids tapering were added.
    07 Sep 2018
    For the AESI ‘opportunistic infections and/or severe infections’, the following text was added as requested by the DMC: ‘Whenever a patient comes to a visit and reports of an (S)AE related to infections, which occurred in the interval since the last visit, then he/she is routinely asked whether they have been seen/treated by a physician and whether blood samples had been taken in that context. Should this be answered in the affirmative, then efforts should be undertaken to collect the respective information’. A statement was added that if a partner of a male trial participant became pregnant this had to be reported and written consent of the pregnant partner was required.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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