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    Clinical Trial Results:
    A Phase IIa, Double-Blind, Mechanistic Study of GSK3196165 in Combination with Methotrexate Therapy in Subjects with Active Rheumatoid Arthritis Despite Treatment with DMARDs

    Summary
    EudraCT number
    		 2015-004386-91
    Trial protocol
    		 DE   PL  
    Global end of trial date
    30 Oct 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Nov 2018
    First version publication date
    13 Nov 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    205180
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343,
    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
    31 Jan 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Oct 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objectives of this study are to explore the activity of Granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway characterized by exploratory biomarkers in participants with rheumatoid arthritis, the impact of GSK3196165 therapy, and whether there are any differences in this GM-CSF signaling pathway between participants with early RA or established RA.
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Jun 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 32
    Country: Number of subjects enrolled
    Poland: 6
    Country: Number of subjects enrolled
    Germany: 1
    Worldwide total number of subjects
    39
    EEA total number of subjects
    7
    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)
    30
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 39 participants with active early/established Rheumatoid arthritis were randomized across 9 centers in 3 countries from 15 June 2016 to 30 October 2017.

    Pre-assignment
    Screening details
    		 Out of the 88 participants screened for this study, 49 participants were screen failures and 39 participants were randomized and received treatment in the study.

    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
    		 Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Eligible participants received matching placebo subcutaneously (SC) into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received methotrexate (MTX) 7.5–25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Sterile 0.9% weight by volume (w/v) sodium chloride solution to be administered as subcutaneous injection into thigh or abdomen once weekly for 5 weeks

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Tablet
    Routes of administration
    Subcutaneous use, Oral use
    Dosage and administration details
    Tablet or liquid administered orally or subcutaneously

    Investigational medicinal product name
    Folic acid or folinic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Tablet, Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    Capsule, tablet or liquid taken orally

    Arm title
    		 GSK3196165 180 mg
    Arm description
    		 Eligible participants received GSK3196165 180 milligrams (mg) SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5–5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK3196165
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GSK3196165 is available as sterile solution to be administered as subcutaneous injection into thigh or abdomen once weekly for 5 weeks.

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Tablet
    Routes of administration
    Subcutaneous use, Oral use
    Dosage and administration details
    Tablet or liquid administered orally or subcutaneously.

    Investigational medicinal product name
    Folic acid or folinic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet, Capsule, Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    Capsule, table or liquid taken orally

    Number of subjects in period 1
    		Placebo GSK3196165 180 mg
    Started
    11
    28
    Completed
    7
    23
    Not completed
    4
    5
         Consent withdrawn by subject
    2
    4
         Lost to follow-up
    -
    1
         Lack of efficacy
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Eligible participants received matching placebo subcutaneously (SC) into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received methotrexate (MTX) 7.5–25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.

    Reporting group title
    GSK3196165 180 mg
    Reporting group description
    		 Eligible participants received GSK3196165 180 milligrams (mg) SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5–5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.

    Reporting group values
    		 Placebo GSK3196165 180 mg Total
    Number of subjects
    		 11 28 39
    Age categorical
    Units: Subjects
        Overall number of baseline subjects
    		 11 28 39
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 50.3 ( 11.57 ) 59.1 ( 9.47 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 10 24 34
        Male
    		 1 4 5
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American|
    		 2 4 6
        White|
    		 9 24 33

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Eligible participants received matching placebo subcutaneously (SC) into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received methotrexate (MTX) 7.5–25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.

    Reporting group title
    GSK3196165 180 mg
    Reporting group description
    		 Eligible participants received GSK3196165 180 milligrams (mg) SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5–5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.

    Primary: Change from Baseline in Target Engagement biomarkers- soluble Granulocyte-macrophage colony-stimulating factor (GM-CSF) complexed to GSK3196165

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    End point title
    		 Change from Baseline in Target Engagement biomarkers- soluble Granulocyte-macrophage colony-stimulating factor (GM-CSF) complexed to GSK3196165
    End point description
    Blood samples were collected for markers which may influence rheumatoid arthritis. Target engagement biomarkers included soluble GM-CSF complexed to GSK3196165. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for GM-CSF - Complex log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Analysis was performed on Intent-to-Treat (ITT) Population which consisted of all participants who were randomized to treatment and who received at least one dose of study treatment. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week follow-up (FU) (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [1]
    28 [2]
    Units: Ratio of GM-CSF complex
    least squares mean (geometric coefficient of variation)
        GM-CSF - Complex, Week 1, n=9, 27|
    0.972 ( 35.98 )
    13.799 ( 20.65 )
        GM-CSF - Complex, Week 2, n=8, 26|
    0.960 ( 31.23 )
    31.056 ( 17.58 )
        GM-CSF - Complex, Week 4, n=8, 27|
    0.959 ( 34.51 )
    53.496 ( 18.55 )
        GM-CSF - Complex, Week 6, n=7, 26|
    0.964 ( 40.96 )
    46.620 ( 22.37 )
        GM-CSF - Complex, Week 8, n=7, 24|
    0.964 ( 41.80 )
    33.404 ( 22.47 )
        GM-CSF - Complex, Week 12, n=7, 24|
    0.970 ( 44.95 )
    22.556 ( 24.38 )
        GM-CSF - Complex, 12-Week FU, n=8, 21|
    0.954 ( 20.80 )
    1.176 ( 12.88 )
    Notes
    [1] - ITT Population
    [2] - ITT Population
    Statistical analysis title
    		 GM-CSF - Complex, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    14.201
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.251
         upper limit
    		 32.262
    Statistical analysis title
    		 GM-CSF - Complex, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    32.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 15.828
         upper limit
    		 66.156
    Statistical analysis title
    		 GM-CSF - Complex, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    55.772
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 25.646
         upper limit
    		 121.287
    Statistical analysis title
    		 GM-CSF - Complex, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    48.336
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 19.341
         upper limit
    		 120.798
    Statistical analysis title
    		 GM-CSF - Complex, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    34.635
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.69
         upper limit
    		 87.629
    Statistical analysis title
    		 GM-CSF - Complex, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    23.249
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.579
         upper limit
    		 63.005
    Statistical analysis title
    		 GM-CSF - Complex, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.401
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.233
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.742
         upper limit
    		 2.048

    Primary: Change from Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9

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    End point title
    		 Change from Baseline in Predictive Biomarkers: 14-3-3 ETA Protein, S100 Calcium Binding Protein (CBP) A8 and A9
    End point description
    Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of 14-3-3 ETA Protein, S100 CBP A8 and A9. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for 14-3-3 ETA Protein (mg/L) and S100 CBP A8 and A9 log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [3]
    28 [4]
    Units: Ratio of predictive biomarker
    least squares mean (geometric coefficient of variation)
        14-3-3 ETA Protein, Week 1, n=9, 27|
    1.046 ( 3.88 )
    0.986 ( 2.16 )
        14-3-3 ETA Protein, Week 2, n=8, 26|
    0.959 ( 12.14 )
    0.986 ( 6.70 )
        14-3-3 ETA Protein, Week 4, n=9, 26|
    1.128 ( 16.59 )
    0.838 ( 9.55 )
        14-3-3 ETA Protein, Week 6, n=7, 26|
    1.093 ( 15.55 )
    0.833 ( 8.88 )
        14-3-3 ETA Protein, Week 8, n=7, 23|
    0.950 ( 15.19 )
    0.842 ( 8.48 )
        14-3-3 ETA Protein, Week 12, n=7, 24|
    1.131 ( 20.90 )
    0.897 ( 11.89 )
        14-3-3 ETA Protein, 12-Week FU, n=7, 21|
    1.040 ( 24.06 )
    0.893 ( 13.45 )
        S100 CBP A8 and A9, Week 1, n=9, 27|
    0.940 ( 15.20 )
    0.939 ( 8.92 )
        S100 CBP A8 and A9, Week 2, n=8, 26|
    0.871 ( 15.28 )
    0.823 ( 8.65 )
        S100 CBP A8 and A9, Week 4, n=9, 27|
    0.874 ( 19.20 )
    0.889 ( 11.26 )
        S100 CBP A8 and A9, Week 6, n=7, 27|
    0.828 ( 21.92 )
    0.812 ( 11.81 )
        S100 CBP A8 and A9, Week 8, n=7, 25|
    0.804 ( 21.04 )
    0.857 ( 11.46 )
        S100 CBP A8 and A9, Week 12, n=7, 24|
    0.694 ( 21.61 )
    0.879 ( 12.05 )
        S100 CBP A8 and A9, 12-Week FU, n=7, 21|
    0.582 ( 20.60 )
    1.018 ( 11.83 )
    Notes
    [3] - ITT Population
    [4] - ITT Population
    Statistical analysis title
    		 14-3-3 ETA Protein, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.193
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.943
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.861
         upper limit
    		 1.032
    Statistical analysis title
    		 14-3-3 ETA Protein, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.842
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.028
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.776
         upper limit
    		 1.362
    Statistical analysis title
    		 14-3-3 ETA Protein, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.127
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.743
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.505
         upper limit
    		 1.093
    Statistical analysis title
    		 14-3-3 ETA Protein, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.137
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.762
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.531
         upper limit
    		 1.095
    Statistical analysis title
    		 14-3-3 ETA Protein, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.488
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.886
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.623
         upper limit
    		 1.259
    Statistical analysis title
    		 14-3-3 ETA Protein, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.338
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.793
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.488
         upper limit
    		 1.29
    Statistical analysis title
    		 14-3-3 ETA Protein, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.582
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.859
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.491
         upper limit
    		 1.502
    Statistical analysis title
    		 S100 CBP A8 and A9, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.996
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.999
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.699
         upper limit
    		 1.427
    Statistical analysis title
    		 S100 CBP A8 and A9, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.745
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.944
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.662
         upper limit
    		 1.346
    Statistical analysis title
    		 S100 CBP A8 and A9, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.939
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.017
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.649
         upper limit
    		 1.593
    Statistical analysis title
    		 S100 CBP A8 and A9, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.937
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.981
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.595
         upper limit
    		 1.617
    Statistical analysis title
    		 S100 CBP A8 and A9, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.787
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.067
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.659
         upper limit
    		 1.727
    Statistical analysis title
    		 S100 CBP A8 and A9, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.342
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.267
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.769
         upper limit
    		 2.086
    Statistical analysis title
    		 S100 CBP A8 and A9, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.026
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.748
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.076
         upper limit
    		 2.838

    Primary: Change from Baseline in Predictive Biomarkers: Amyloid A

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    End point title
    		 Change from Baseline in Predictive Biomarkers: Amyloid A
    End point description
    Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of Amyloid A. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for Amyloid A log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data has been presented for only those time points at which the samples were collected.
    End point type
    Primary
    End point timeframe
    Baseline and Week 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [5]
    28 [6]
    Units: Ratio of predictive biomarker
    least squares mean (geometric coefficient of variation)
        Amyloid A, Week 12, n=7, 24|
    0.845 ( 49.31 )
    0.653 ( 25.45 )
        Amyloid A, 12-Week FU, n=7, 21|
    0.529 ( 35.12 )
    0.623 ( 19.68 )
    Notes
    [5] - ITT Population
    [6] - ITT Population
    Statistical analysis title
    		 Amyloid A, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.632
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.774
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.261
         upper limit
    		 2.29
    Statistical analysis title
    		 Amyloid A, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.685
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.176
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.519
         upper limit
    		 2.663

    Primary: Change from Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine

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    End point title
    		 Change from Baseline in Predictive Biomarkers: Amyloid A, Chemokine (C-C Motif) Ligand 17, Chemokine (C-X-C Motif) Ligand 13, Interleukin 6, Macrophage-Derived Chemokine
    End point description
    Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of Chemokine (C-C Motif) Ligand 17 (CL17), Chemokine (C-X-C Motif) Ligand 13 (CL13), Interleukin 6, Macrophage-Derived Chemokine (MDC). Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for CL17, CL13, Interleukin 6, MDC log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data has been presented for only those time points at which the samples were collected.
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [7]
    28 [8]
    Units: Ratio of predictive biomarker
    least squares mean (geometric coefficient of variation)
        CL17, Week 1, n=9, 27|
    1.117 ( 18.81 )
    0.773 ( 10.94 )
        CL17, Week 2, n=8, 26|
    0.912 ( 24.37 )
    0.651 ( 13.60 )
        CL17, Week 4, n=9, 27|
    1.117 ( 21.91 )
    0.679 ( 12.51 )
        CL17, Week 6, n=7, 27|
    1.032 ( 24.38 )
    0.779 ( 12.48 )
        CL17, Week 8, n=7, 25|
    1.211 ( 20.63 )
    0.675 ( 11.21 )
        CL17, Week 12, n=7, 24|
    1.711 ( 24.96 )
    0.890 ( 13.90 )
        CL17, 12-Week FU, n=7, 20|
    1.434 ( 23.26 )
    1.357 ( 13.59 )
        CL13, Week 1, n=9, 27|
    1.198 ( 15.63 )
    0.915 ( 8.87 )
        CL13, Week 2, n=8, 26|
    1.090 ( 13.98 )
    1.095 ( 7.78 )
        CL13, Week 4, n=9, 27|
    0.947 ( 15.58 )
    1.170 ( 8.90 )
        CL13, Week 6, n=7, 27|
    0.839 ( 17.20 )
    1.038 ( 8.91 )
        CL13, Week 8, n=7, 25|
    0.913 ( 23.70 )
    1.021 ( 12.38 )
        CL13, Week 12, n=7,24|
    0.924 ( 31.17 )
    1.077 ( 16.31 )
        CL13, 12-Week FU, n=7,21|
    0.774 ( 27.82 )
    1.224 ( 15.04 )
        Interleukin 6, Week 1, n=9, 26|
    1.179 ( 27.92 )
    1.064 ( 16.38 )
        Interleukin 6, Week 2, n=8, 26|
    1.153 ( 29.33 )
    0.830 ( 16.63 )
        Interleukin 6, Week 4, n=9, 27|
    0.986 ( 26.22 )
    0.811 ( 15.10 )
        Interleukin 6, Week 6, n=7, 27|
    1.136 ( 24.95 )
    0.748 ( 13.51 )
        Interleukin 6, Week 8, n=7, 25|
    1.275 ( 23.65 )
    0.872 ( 13.35 )
        Interleukin 6, Week 12, n=7, 24|
    0.770 ( 21.89 )
    0.939 ( 12.35 )
        Interleukin 6, 12-Week FU, n=7, 21|
    0.817 ( 33.13 )
    1.308 ( 18.63 )
        MDC, Week 1, n=9, 27|
    0.987 ( 5.02 )
    0.914 ( 2.89 )
        MDC, Week 2, n=8, 26|
    0.925 ( 7.33 )
    0.911 ( 4.15 )
        MDC, Week 4, n=9, 27|
    0.936 ( 8.13 )
    0.895 ( 4.67 )
        MDC, Week 6, n=7, 27|
    0.984 ( 8.38 )
    0.994 ( 4.48 )
        MDC, Week 8, n=7, 25|
    1.049 ( 9.36 )
    0.899 ( 5.09 )
        MDC, Week 12, n=7, 24|
    1.245 ( 9.51 )
    1.058 ( 5.23 )
        MDC, 12-Week FU, n=7, 20|
    1.303 ( 12.66 )
    1.321 ( 7.53 )
    Notes
    [7] - ITT Population
    [8] - ITT Population
    Statistical analysis title
    		 CL17, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.097
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.692
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.445
         upper limit
    		 1.074
    Statistical analysis title
    		 CL17, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.229
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.713
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.407
         upper limit
    		 1.249
    Statistical analysis title
    		 CL17, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.055
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.608
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.365
         upper limit
    		 1.012
    Statistical analysis title
    		 CL17, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.307
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.755
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.435
         upper limit
    		 1.309
    Statistical analysis title
    		 CL17, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.017
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.557
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.348
         upper limit
    		 0.894
    Statistical analysis title
    		 CL17, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.026
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.294
         upper limit
    		 0.922
    Statistical analysis title
    		 CL17, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.839
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.947
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.548
         upper limit
    		 1.636
    Statistical analysis title
    		 CL13, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.142
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.764
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1.1
    Statistical analysis title
    		 CL13, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.976
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.005
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.726
         upper limit
    		 1.39
    Statistical analysis title
    		 CL13, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.244
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.236
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.859
         upper limit
    		 1.778
    Statistical analysis title
    		 CL13, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.278
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.237
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.836
         upper limit
    		 1.83
    Statistical analysis title
    		 CL13, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.677
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.118
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.651
         upper limit
    		 1.92
    Statistical analysis title
    		 CL13, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.661
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.165
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.573
         upper limit
    		 2.369
    Statistical analysis title
    		 CL13, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.154
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.581
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.832
         upper limit
    		 3.007
    Statistical analysis title
    		 Interleukin 6, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.751
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.903
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.471
         upper limit
    		 1.729
    Statistical analysis title
    		 Interleukin 6, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.33
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.367
         upper limit
    		 1.413
    Statistical analysis title
    		 Interleukin 6, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.519
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.822
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.447
         upper limit
    		 1.512
    Statistical analysis title
    		 Interleukin 6, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.147
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.659
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.372
         upper limit
    		 1.167
    Statistical analysis title
    		 Interleukin 6, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.166
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.684
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.396
         upper limit
    		 1.18
    Statistical analysis title
    		 Interleukin 6, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.432
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.221
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.734
         upper limit
    		 2.031
    Statistical analysis title
    		 Interleukin 6, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.216
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.602
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 3.423
    Statistical analysis title
    		 MDC, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.195
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.926
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.823
         upper limit
    		 1.042
    Statistical analysis title
    		 MDC, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.851
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.984
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.829
         upper limit
    		 1.168
    Statistical analysis title
    		 MDC, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.637
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.956
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.158
    Statistical analysis title
    		 MDC, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.915
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.833
         upper limit
    		 1.225
    Statistical analysis title
    		 MDC, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.157
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.857
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.064
    Statistical analysis title
    		 MDC, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.142
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.849
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.681
         upper limit
    		 1.059
    Statistical analysis title
    		 MDC, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.929
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.013
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.745
         upper limit
    		 1.378

    Primary: Change from Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)

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    End point title
    		 Change from Baseline in Predictive Biomarkers: Chitinase 3 Like 1, Matrix Metalloproteinase 3 (MMP-3)
    End point description
    Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Predictive biomarkers included analysis of Chitinase 3 Like 1 and MMP-3. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for Chitinase 3 Like 1 and MMP-3 log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [9]
    28 [10]
    Units: Ratio of predictive biomarker
    least squares mean (geometric coefficient of variation)
        Chitinase 3 Like 1, Week 1, n=9, 27|
    1.033 ( 13.97 )
    0.917 ( 8.13 )
        Chitinase 3 Like 1, Week 2, n=8, 26|
    1.013 ( 15.05 )
    0.966 ( 8.55 )
        Chitinase 3 Like 1, Week 4, n=9, 27|
    0.961 ( 17.14 )
    1.088 ( 9.96 )
        Chitinase 3 Like 1, Week 6, n=7, 27|
    0.897 ( 17.08 )
    1.031 ( 8.80 )
        Chitinase 3 Like 1, Week 8, n=7, 25|
    0.851 ( 18.24 )
    0.947 ( 9.70 )
        Chitinase 3 Like 1, Week 12, n=7, 24|
    1.066 ( 21.53 )
    1.071 ( 11.64 )
        Chitinase 3 Like 1, 12-Week FU, n=7, 21|
    0.735 ( 16.87 )
    1.019 ( 9.75 )
        MMP 3, Week 1, n=9, 27|
    1.076 ( 6.72 )
    0.984 ( 3.88 )
        MMP-3, Week 2, n=8, 26|
    1.067 ( 7.26 )
    1.024 ( 4.09 )
        MMP-3, Week 4, n=9, 27|
    1.112 ( 8.30 )
    1.016 ( 4.73 )
        MMP-3, Week 6, n=7, 27|
    1.005 ( 26.26 )
    0.804 ( 13.44 )
        MMP-3, Week 8, n=7, 25|
    0.939 ( 15.43 )
    1.088 ( 8.21 )
        MMP-3, Week 12, n=7, 24|
    1.000 ( 13.57 )
    0.951 ( 7.35 )
        MMP-3, 12-Week FU, n=7, 21|
    0.803 ( 16.05 )
    0.984 ( 9.00 )
    Notes
    [9] - ITT Population
    [10] - ITT Population
    Statistical analysis title
    		 Chitinase 3 Like 1, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.463
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.887
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.231
    Statistical analysis title
    		 Chitinase 3 Like 1, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.782
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.953
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.672
         upper limit
    		 1.352
    Statistical analysis title
    		 Chitinase 3 Like 1, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.533
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.132
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.759
         upper limit
    		 1.69
    Statistical analysis title
    		 Chitinase 3 Like 1, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.473
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.149
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.779
         upper limit
    		 1.694
    Statistical analysis title
    		 Chitinase 3 Like 1, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.608
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.112
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.733
         upper limit
    		 1.687
    Statistical analysis title
    		 Chitinase 3 Like 1, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.985
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.005
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.613
         upper limit
    		 1.645
    Statistical analysis title
    		 Chitinase 3 Like 1, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.102
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.386
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.934
         upper limit
    		 2.057
    Statistical analysis title
    		 MMP-3, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.259
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.915
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.781
         upper limit
    		 1.071
    Statistical analysis title
    		 MMP-3, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.621
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.959
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.809
         upper limit
    		 1.137
    Statistical analysis title
    		 MMP-3, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.354
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.914
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.752
         upper limit
    		 1.11
    Statistical analysis title
    		 MMP-3, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.448
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.443
         upper limit
    		 1.444
    Statistical analysis title
    		 MMP-3, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.402
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.813
         upper limit
    		 1.653
    Statistical analysis title
    		 MMP-3, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.745
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.951
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.695
         upper limit
    		 1.301
    Statistical analysis title
    		 MMP-3, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.279
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.226
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.837
         upper limit
    		 1.796

    Primary: Change from Baseline in Cartilage Biomarkers

    		 Close Top of page
    End point title
    		 Change from Baseline in Cartilage Biomarkers
    End point description
    Blood samples were collected and analyzed for markers that may be predictive of rheumatoid arthritis disease activity. Cartilage biomarkers included analysis of ARGS Neo-Epitope, Citrullinated MMP-Degraded Vimentin (CMDV), MMP-Degraded C Reactive Protein (CRP), MMP-Degraded Type I Collagen (MD1C), MMP-Degraded Type II Collagen (MD2C), MMP-Degraded Type III Collagen (MD3C). Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for ARGS Neo-Epitope, Citrullinated MMP-Degraded Vimentin, MMP-Degraded CRP, MMP-Degraded Type I Collagen, MMP-Degraded Type II Collagen and MMP-Degraded Type III Collagen log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [11]
    28 [12]
    Units: Ratio of cartilage biomarker
    least squares mean (geometric coefficient of variation)
        ARGS Neo-Epitope, Week 1, n=9, 27|
    0.979 ( 16.10 )
    1.075 ( 9.67 )
        ARGS Neo-Epitope, Week 2, n=8, 25|
    0.790 ( 17.38 )
    1.249 ( 9.87 )
        ARGS Neo-Epitope, Week 4, n=8, 26|
    0.904 ( 17.02 )
    1.104 ( 10.05 )
        ARGS Neo-Epitope, Week 6, n=6, 26|
    0.894 ( 14.28 )
    1.164 ( 7.82 )
        ARGS Neo-Epitope, Week 8, n=7, 24|
    0.854 ( 26.42 )
    1.238 ( 14.20 )
        ARGS Neo-Epitope, Week 12, n=7, 24|
    0.913 ( 13.97 )
    1.156 ( 7.78 )
        ARGS Neo-Epitope, 12-Week FU, n=8, 21|
    1.129 ( 17.44 )
    1.124 ( 9.86 )
        CMDV, Week 1,n=9,27|
    0.981 ( 24.12 )
    0.876 ( 13.80 )
        CMDV,Week 2,n=8,26|
    0.820 ( 28.46 )
    0.714 ( 15.89 )
        CMDV, Week 4,n=9,27|
    0.715 ( 27.30 )
    0.801 ( 15.52 )
        CMDV, Week 6,n=7,27|
    1.099 ( 30.47 )
    0.726 ( 15.94 )
        CMDV, Week 8,n=7,25|
    0.929 ( 24.72 )
    0.759 ( 13.39 )
        CMDV, Week12,n=7,24|
    1.123 ( 29.34 )
    0.917 ( 16.00 )
        CMDV, 12-Week FU,n=7,21|
    0.936 ( 28.05 )
    0.769 ( 15.81 )
        MMP-Degraded CRP, Week 1, n=9, 27|
    0.971 ( 6.83 )
    1.021 ( 3.99 )
        MMP-Degraded CRP, Week 2, n=8, 26|
    0.970 ( 5.55 )
    1.000 ( 3.07 )
        MMP-Degraded CRP, Week 4, n=9, 27|
    0.992 ( 6.01 )
    1.004 ( 3.49 )
        MMP-Degraded CRP, Week 6, n=7, 27|
    1.122 ( 6.55 )
    1.099 ( 3.50 )
        MMP-Degraded CRP, Week 8, n=7, 25|
    0.977 ( 7.37 )
    1.087 ( 4.05 )
        MMP-Degraded CRP, Week 12, n=7, 24|
    1.006 ( 7.13 )
    1.108 ( 3.95 )
        MMP-Degraded CRP, 12-Week FU, n=7, 21|
    1.075 ( 8.01 )
    1.129 ( 4.48 )
        MD1C, Week 1, n=9, 27|
    1.079 ( 9.60 )
    0.858 ( 5.63 )
        MD1C, Week 2, n=8, 26|
    1.028 ( 11.98 )
    0.907 ( 6.63 )
        MD1C, Week 4, n=9, 27|
    1.142 ( 14.57 )
    0.896 ( 8.35 )
        MD1C, Week 6, n=7, 27|
    1.392 ( 12.64 )
    0.889 ( 6.98 )
        MD1C, Week 8, n=7, 25|
    1.131 ( 13.05 )
    0.904 ( 7.23 )
        MD1C, Week 12, n=7, 24|
    1.148 ( 13.74 )
    1.023 ( 7.81 )
        MD1C, 12-Week FU, n=7, 21|
    1.095 ( 14.21 )
    0.952 ( 8.31 )
        MD2C, Week 1, n=9, 27|
    1.059 ( 11.83 )
    1.038 ( 6.88 )
        MD2C, Week 2, n=8, 26|
    1.046 ( 11.27 )
    1.015 ( 6.28 )
        MD2C, Week 4, n=9, 27|
    1.035 ( 10.18 )
    1.003 ( 5.86 )
        MD2C, Week 6, n=7, 27|
    1.158 ( 12.07 )
    1.064 ( 6.30 )
        MD2C, Week 8, n=7, 25|
    1.091 ( 11.42 )
    1.023 ( 6.12 )
        MD2C, Week 12, n=7, 24|
    1.174 ( 10.73 )
    1.072 ( 5.87 )
        MD2C, 12-Week FU, n=7, 21|
    1.338 ( 13.10 )
    1.041 ( 7.50 )
        MD3C, Week 1, n=9, 27|
    0.950 ( 6.44 )
    0.959 ( 3.74 )
        MD3C, Week 2, n=8, 26|
    0.920 ( 6.82 )
    0.954 ( 3.91 )
        MD3C, Week 4, n=9, 27|
    0.940 ( 8.06 )
    0.886 ( 4.68 )
        MD3C, Week 6, n=7, 27|
    1.013 ( 8.09 )
    0.894 ( 4.34 )
        MD3C, Week 8, n=7, 25|
    0.918 ( 9.04 )
    0.881 ( 4.84 )
        MD3C, Week 12, n=7, 24|
    0.929 ( 9.28 )
    0.910 ( 5.08 )
        MD3C, 12-Week FU, n=7, 21|
    0.847 ( 9.75 )
    0.910 ( 5.46 )
    Notes
    [11] - ITT Population
    [12] - ITT Population
    Statistical analysis title
    		 ARGS Neo-Epitope, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.621
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.098
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.606
    Statistical analysis title
    		 ARGS Neo-Epitope, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.031
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.581
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.046
         upper limit
    		 2.388
    Statistical analysis title
    		 ARGS Neo-Epitope, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.317
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.222
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.817
         upper limit
    		 1.827
    Statistical analysis title
    		 ARGS Neo-Epitope, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.113
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.302
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.936
         upper limit
    		 1.81
    Statistical analysis title
    		 ARGS Neo-Epitope, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.217
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.795
         upper limit
    		 2.645
    Statistical analysis title
    		 ARGS Neo-Epitope, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.147
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.266
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.916
         upper limit
    		 1.75
    Statistical analysis title
    		 ARGS Neo-Epitope, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.985
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.996
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.662
         upper limit
    		 1.499
    Statistical analysis title
    		 CMDV, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.681
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.892
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.511
         upper limit
    		 1.56
    Statistical analysis title
    		 CMDV, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.668
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.454
         upper limit
    		 1.669
    Statistical analysis title
    		 CMDV, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.717
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.597
         upper limit
    		 2.101
    Statistical analysis title
    		 CMDV, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.227
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.661
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.333
         upper limit
    		 1.31
    Statistical analysis title
    		 CMDV, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.471
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.817
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.464
         upper limit
    		 1.437
    Statistical analysis title
    		 CMDV, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.541
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.816
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.417
         upper limit
    		 1.597
    Statistical analysis title
    		 CMDV, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.544
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.822
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.422
         upper limit
    		 1.602
    Statistical analysis title
    		 MMP-Degraded CRP, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.537
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.051
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.895
         upper limit
    		 1.233
    Statistical analysis title
    		 MMP-Degraded CRP, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.635
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.031
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.906
         upper limit
    		 1.173
    Statistical analysis title
    		 MMP-Degraded CRP, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.866
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.012
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.879
         upper limit
    		 1.165
    Statistical analysis title
    		 MMP-Degraded CRP, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.78
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.979
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.842
         upper limit
    		 1.139
    Statistical analysis title
    		 MMP-Degraded CRP, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.212
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.113
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.938
         upper limit
    		 1.32
    Statistical analysis title
    		 MMP-Degraded CRP, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.242
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.102
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.934
         upper limit
    		 1.3
    Statistical analysis title
    		 MMP-Degraded CRP, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.597
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.267
    Statistical analysis title
    		 MD1C, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.047
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.795
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.634
         upper limit
    		 0.997
    Statistical analysis title
    		 MD1C, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.367
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.883
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.668
         upper limit
    		 1.165
    Statistical analysis title
    		 MD1C, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.155
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.784
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.558
         upper limit
    		 1.102
    Statistical analysis title
    		 MD1C, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.004
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.638
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.477
         upper limit
    		 0.855
    Statistical analysis title
    		 MD1C, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.14
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.799
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.591
         upper limit
    		 1.08
    Statistical analysis title
    		 MD1C, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.47
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.891
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.647
         upper limit
    		 1.228
    Statistical analysis title
    		 MD1C, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.401
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.869
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.621
         upper limit
    		 1.217
    Statistical analysis title
    		 MD2C, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.887
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.981
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.742
         upper limit
    		 1.296
    Statistical analysis title
    		 MD2C, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.814
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.744
         upper limit
    		 1.263
    Statistical analysis title
    		 MD2C, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.794
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.969
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.762
         upper limit
    		 1.233
    Statistical analysis title
    		 MD2C, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.539
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.919
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.696
         upper limit
    		 1.213
    Statistical analysis title
    		 MD2C, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.623
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.937
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.719
         upper limit
    		 1.221
    Statistical analysis title
    		 MD2C, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.467
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.913
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.711
         upper limit
    		 1.173
    Statistical analysis title
    		 MD2C, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.108
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.778
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 1.061
    Statistical analysis title
    		 MD3C, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.897
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.868
         upper limit
    		 1.175
    Statistical analysis title
    		 MD3C, Week 2
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.644
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.037
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.884
         upper limit
    		 1.218
    Statistical analysis title
    		 MD3C, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.53
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.943
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.139
    Statistical analysis title
    		 MD3C, Week 6
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.182
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.882
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.733
         upper limit
    		 1.063
    Statistical analysis title
    		 MD3C, Week 8
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.691
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.779
         upper limit
    		 1.182
    Statistical analysis title
    		 MD3C, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.843
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.979
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.214
    Statistical analysis title
    		 MD3C, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.524
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.075
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.855
         upper limit
    		 1.351

    Primary: Change from Baseline in Flow Cytometry: Helper/Suppressor cells

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    End point title
    		 Change from Baseline in Flow Cytometry: Helper/Suppressor cells
    End point description
    Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of Helper/Suppressor. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for Helper/Suppressor log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [13]
    28 [14]
    Units: Ratio of Helper/Suppressor cells
    least squares mean (geometric coefficient of variation)
        Helper/Suppressor, Week 1, n=8, 25|
    1.024 ( 6.98 )
    0.976 ( 4.00 )
        Helper/Suppressor, Week 4, n=8, 25|
    1.053 ( 7.18 )
    0.998 ( 4.11 )
        Helper/Suppressor, Week 12, n=6, 25|
    1.040 ( 6.83 )
    1.088 ( 3.49 )
        Helper/Suppressor, 12-Week FU, n=6, 21|
    1.051 ( 8.99 )
    1.065 ( 4.88 )
    Notes
    [13] - ITT Population
    [14] - ITT Population
    Statistical analysis title
    		 Helper/Suppressor, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.558
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.953
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.809
         upper limit
    		 1.123
    Statistical analysis title
    		 Helper/Suppressor, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.515
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.947
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.801
         upper limit
    		 1.12
    Statistical analysis title
    		 Helper/Suppressor, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.565
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.046
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.895
         upper limit
    		 1.222
    Statistical analysis title
    		 Helper/Suppressor, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.897
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.013
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.822
         upper limit
    		 1.249

    Primary: Change from Baseline in Flow Cytometry: 6 Colour TB natural killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+

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    End point title
    		 Change from Baseline in Flow Cytometry: 6 Colour TB natural killer (NK) Panel- CD16+CD56+, CD19, CD3, CD3+CD4+
    End point description
    Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of cluster of differentiation (CD)16+CD56+, CD19, CD3, CD3+CD4+. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Repeated measures analysis adjusted for CD16+CD56+, CD19, CD3, CD3+CD4+, CD3+CD8+ and T Cell B Cell NKL log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [15]
    28 [16]
    Units: Ratio of biomarker
    least squares mean (geometric coefficient of variation)
        CD16+CD56+, Week 1, n=8, 25|
    0.989 ( 11.39 )
    1.025 ( 6.30 )
        CD16+CD56+, Week 4, n=8, 25|
    1.163 ( 12.97 )
    0.951 ( 7.25 )
        CD16+CD56+, Week 12, n=6, 25|
    1.193 ( 15.49 )
    0.911 ( 7.81 )
        CD16+CD56+, 12-Week FU, n=6, 21|
    1.298 ( 15.10 )
    0.920 ( 7.98 )
        CD19, Week 1, n=8, 25|
    0.880 ( 11.05 )
    0.984 ( 6.23 )
        CD19, Week 4, n=8, 25|
    1.090 ( 15.31 )
    0.971 ( 8.60 )
        CD19, Week 12, n=6, 25|
    1.054 ( 12.26 )
    1.003 ( 6.51 )
        CD19, Week 22, n=6, 21|
    0.980 ( 17.75 )
    0.938 ( 9.75 )
        CD3, Week 1, n=8, 25|
    0.918 ( 8.73 )
    0.994 ( 4.95 )
        CD3, Week 4, n=8, 25|
    0.997 ( 11.79 )
    0.934 ( 6.66 )
        CD3, Week 12, n=6, 25|
    0.912 ( 9.01 )
    0.992 ( 4.60 )
        CD3, 12-Week FU, n=6, 21|
    0.931 ( 9.17 )
    0.989 ( 4.98 )
        CD3+CD4+, Week 1, n=8, 25|
    0.926 ( 9.56 )
    0.991 ( 5.42 )
        CD3+CD4+, Week 4, n=8, 25|
    1.028 ( 12.80 )
    0.933 ( 7.23 )
        CD3+CD4+, Week 12, n=6, 25|
    0.952 ( 9.69 )
    1.013 ( 4.94 )
        CD3+CD4+, 12-Week FU, n=6, 21|
    0.970 ( 9.92 )
    1.000 ( 5.37 )
    Notes
    [15] - ITT Population
    [16] - ITT Population
    Statistical analysis title
    		 CD16+CD56+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.786
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.037
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.794
         upper limit
    		 1.354
    Statistical analysis title
    		 CD16+CD56+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.188
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.818
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.603
         upper limit
    		 1.109
    Statistical analysis title
    		 CD16+CD56+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.129
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.763
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.536
         upper limit
    		 1.087
    Statistical analysis title
    		 CD16+CD56+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.054
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.709
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.499
         upper limit
    		 1.006
    Statistical analysis title
    		 CD19, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.383
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.119
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.863
         upper limit
    		 1.45
    Statistical analysis title
    		 CD19, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.51
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.623
         upper limit
    		 1.271
    Statistical analysis title
    		 CD19, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.724
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.952
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.718
         upper limit
    		 1.262
    Statistical analysis title
    		 CD19, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.831
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.958
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.635
         upper limit
    		 1.443
    Statistical analysis title
    		 CD3, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.437
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.082
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.882
         upper limit
    		 1.328
    Statistical analysis title
    		 CD3, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.632
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.937
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.711
         upper limit
    		 1.234
    Statistical analysis title
    		 CD3, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.413
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.088
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.885
         upper limit
    		 1.336
    Statistical analysis title
    		 CD3, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.567
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.062
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.858
         upper limit
    		 1.316
    Statistical analysis title
    		 CD3+CD4+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.547
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.069
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.855
         upper limit
    		 1.338
    Statistical analysis title
    		 CD3+CD4+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.512
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.907
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.673
         upper limit
    		 1.223
    Statistical analysis title
    		 CD3+CD4+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.573
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.064
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.853
         upper limit
    		 1.328
    Statistical analysis title
    		 CD3+CD4+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.789
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.031
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.818
         upper limit
    		 1.3

    Primary: Change from Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)

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    End point title
    		 Change from Baseline in Flow Cytometry: 6 Colour TBNK Panel- CD3+CD8+ and T Cell B Cell Natural Killer Lymphocytes (NKL)
    End point description
    Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of CD3+CD8+ and T Cell B Cell NKL. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for CD3+CD8+ and T Cell B Cell NKL log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [17]
    28 [18]
    Units: 10^9 cells/Liter
    least squares mean (standard error)
        CD3+CD8+, Week 1, n=8, 25|
    -0.041 ( 0.0390 )
    -0.005 ( 0.0222 )
        CD3+CD8+, Week 4, n=8, 25|
    0.000 ( 0.0580 )
    -0.023 ( 0.0327 )
        CD3+CD8+, Week 12, n=6, 25|
    -0.056 ( 0.0418 )
    -0.037 ( 0.0215 )
        CD3+CD8+, 12-Week FU, n=6, 21|
    -0.060 ( 0.0506 )
    -0.027 ( 0.0279 )
        T Cell B Cell NKL, Week 1, n=8, 25|
    -0.123 ( 0.1557 )
    -0.020 ( 0.0881 )
        T Cell B Cell NKL, Week 4, n=8, 25|
    0.108 ( 0.2174 )
    -0.050 ( 0.1229 )
        T Cell B Cell NKL, Week 12, n=6, 25|
    -0.093 ( 0.1792 )
    -0.006 ( 0.0925 )
        T Cell B Cell NKL, 12-Week FU, n=6, 21|
    -0.029 ( 0.2168 )
    -0.050 ( 0.1183 )
    Notes
    [17] - ITT Population
    [18] - ITT Population
    Statistical analysis title
    		 CD3+CD8+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.428
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.036
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.056
         upper limit
    		 0.128
    Statistical analysis title
    		 CD3+CD8+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.733
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.023
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.159
         upper limit
    		 0.113
    Statistical analysis title
    		 CD3+CD8+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.677
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.076
         upper limit
    		 0.115
    Statistical analysis title
    		 CD3+CD8+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.569
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.033
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.084
         upper limit
    		 0.151
    Statistical analysis title
    		 T Cell B Cell NKL, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.569
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.103
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.263
         upper limit
    		 0.469
    Statistical analysis title
    		 T Cell B Cell NKL, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.534
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.157
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.668
         upper limit
    		 0.354
    Statistical analysis title
    		 T Cell B Cell NKL, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.668
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.087
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.323
         upper limit
    		 0.498
    Statistical analysis title
    		 T Cell B Cell NKL, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.934
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.021
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.526
         upper limit
    		 0.484

    Primary: Change from Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+

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    End point title
    		 Change from Baseline in Flow Cytometry: T Regulatory (Reg) Cell Foxp3- CD3+ CD4+, CD3+ CD8+ and CD3+
    End point description
    Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of CD3+ CD4+, CD3+ CD8+ and CD3+. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Analysis was performed using repeated measures analysis adjusted for CD3+ CD4+, CD3+ CD8+ and CD3+ Number of Cells (10^6/L) log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [19]
    28 [20]
    Units: Ratio of T Reg cell
    least squares mean (geometric coefficient of variation)
        CD3+ CD4+, Week 1, n=7, 23|
    0.905 ( 10.21 )
    1.007 ( 5.65 )
        CD3+ CD4+, Week 4, n=7, 22|
    1.038 ( 11.31 )
    0.976 ( 6.38 )
        CD3+ CD4+, Week 12, n=5, 21|
    0.981 ( 10.55 )
    1.004 ( 5.31 )
        CD3+ CD4+, 12-Week FU, n=5, 17|
    0.926 ( 11.70 )
    1.003 ( 6.39 )
        CD3+ CD8+, Week 1, n=7, 23|
    0.885 ( 9.97 )
    0.983 ( 5.50 )
        CD3+ CD8+, Week 4, n=7, 22|
    0.981 ( 11.89 )
    0.939 ( 6.66 )
        CD3+ CD8+, Week 12, n=5, 21|
    0.878 ( 10.50 )
    0.945 ( 5.40 )
        CD3+ CD8+, 12-Week FU, n=5, 17|
    0.936 ( 10.99 )
    0.965 ( 6.05 )
        CD3+, Week 1, n=7, 23|
    0.901 ( 9.98 )
    0.992 ( 5.54 )
        CD3+, Week 4, n=7, 22|
    1.034 ( 12.99 )
    0.938 ( 7.33 )
        CD3+, Week 12, n=5, 21|
    0.959 ( 9.62 )
    0.993 ( 4.90 )
        CD3+, 12-Week FU, n=5, 17|
    0.944 ( 10.88 )
    0.991 ( 6.00 )
    Notes
    [19] - ITT Population
    [20] - ITT Population
    Statistical analysis title
    		 CD3+ CD4+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.369
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.112
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.876
         upper limit
    		 1.412
    Statistical analysis title
    		 CD3+ CD4+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.641
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.941
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.721
         upper limit
    		 1.228
    Statistical analysis title
    		 CD3+ CD4+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.844
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.024
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.804
         upper limit
    		 1.303
    Statistical analysis title
    		 CD3+ CD4+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.558
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.082
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.821
         upper limit
    		 1.427
    Statistical analysis title
    		 CD3+ CD8+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.363
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.111
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.402
    Statistical analysis title
    		 CD3+ CD8+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.751
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.957
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.724
         upper limit
    		 1.265
    Statistical analysis title
    		 CD3+ CD8+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.537
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.076
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.846
         upper limit
    		 1.37
    Statistical analysis title
    		 CD3+ CD8+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.806
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.032
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.797
         upper limit
    		 1.335
    Statistical analysis title
    		 CD3+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.405
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.101
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.872
         upper limit
    		 1.391
    Statistical analysis title
    		 CD3+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.519
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    0.907
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.668
         upper limit
    		 1.232
    Statistical analysis title
    		 CD3+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.748
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.036
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.831
         upper limit
    		 1.291
    Statistical analysis title
    		 CD3+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.704
    Method
    		 Repeated measures analysis
    Parameter type
    		 Ratio
    Point estimate
    1.049
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.811
         upper limit
    		 1.356

    Primary: Change from Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-

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    End point title
    		 Change from Baseline in Flow Cytometry: T Reg Cell Foxp3: CD3+CD4+CD25+CD127-, CD3+CD4+foxP3+CD25+CD127-
    End point description
    Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of CD3+CD4+CD25+CD127- and CD3+CD4+foxP3+CD25+CD127-. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for CD3+CD4+CD25+CD127- and CD3+CD4+foxP3+CD25+CD127-Number of Cells (10^6 cells/L) log(Baseline value), treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [21]
    28 [22]
    Units: 10^6 cells/Liter
    least squares mean (standard error)
        CD3+CD4+CD25+CD127-, Week 1, n=7, 23|
    -3.6 ( 8.35 )
    2.9 ( 4.67 )
        CD3+CD4+CD25+CD127-, Week 4, n=7, 22|
    1.4 ( 8.34 )
    -0.4 ( 4.70 )
        CD3+CD4+CD25+CD127-, Week 12, n=5, 21|
    -9.4 ( 9.87 )
    -3.1 ( 4.94 )
        CD3+CD4+CD25+CD127-, 12-Week FU, n=5, 17|
    -12.9 ( 9.92 )
    -2.3 ( 5.43 )
        CD3+CD4+foxP3+CD25+CD127, Week 1, n=7, 23|
    0.8 ( 6.39 )
    2.8 ( 3.58 )
        CD3+CD4+foxP3+CD25+CD127, Week 4, n=7, 22|
    4.3 ( 7.05 )
    2.0 ( 3.98 )
        CD3+CD4+foxP3+CD25+CD127, Week 12, n=5, 21|
    2.7 ( 7.99 )
    -4.4 ( 3.91 )
        CD3+CD4+foxP3+CD25+CD127,12-Week FU, n=5,17|
    -8.7 ( 5.94 )
    -4.6 ( 3.15 )
    Notes
    [21] - ITT Population
    [22] - ITT Population
    Statistical analysis title
    		 CD3+CD4+CD25+CD127-, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.501
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    6.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.1
         upper limit
    		 26.1
    Statistical analysis title
    		 CD3+CD4+CD25+CD127-, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.852
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.6
         upper limit
    		 18
    Statistical analysis title
    		 CD3+CD4+CD25+CD127-, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.572
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    6.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.4
         upper limit
    		 29
    Statistical analysis title
    		 CD3+CD4+CD25+CD127-, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.363
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    10.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13
         upper limit
    		 34.1
    Statistical analysis title
    		 CD3+CD4+foxP3+CD25+CD127-, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.788
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13
         upper limit
    		 17
    Statistical analysis title
    		 CD3+CD4+foxP3+CD25+CD127-, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.786
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.8
         upper limit
    		 14.4
    Statistical analysis title
    		 CD3+CD4+foxP3+CD25+CD127-, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.433
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -7.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.4
         upper limit
    		 11.2
    Statistical analysis title
    		 CD3+CD4+foxP3+CD25+CD127-, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.55
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    4.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.8
         upper limit
    		 18

    Primary: Change from Baseline in T Helper Cell Panel events

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    End point title
    		 Change from Baseline in T Helper Cell Panel events
    End point description
    Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. T Helper Cell Panel included analysis of CD45+3+8-4+CCR6+CXCR3+38+DR+, CD45+3+8-4+CCR6+CXCR3-38+DR+, CD45+3+8-4+CCR6-CXCR3+38+DR+, CD45+3+8-4+CCR6-CXCR3-38+DR+, CD45+CD3+CD8-CD4+, CD45+CD3+CD8-CD4+CCR6+CXCR3+, CD45+CD3+CD8-CD4+CCR6+CXCR3-, CD45+CD3+CD8-CD4+CCR6-CXCR3+ and CD45+CD3+CD8-CD4+CCR6-CXCR3-. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for T Helper Cell Panel Events (EVENTS) Baseline value, treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [23]
    28 [24]
    Units: Events
    least squares mean (standard error)
        CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 1, n=7, 23|
    -48.6 ( 13.50 )
    -34.0 ( 7.35 )
        CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 4, n=7, 21|
    -14.5 ( 18.36 )
    -6.1 ( 10.63 )
        CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 12, n=5, 22|
    42.3 ( 37.80 )
    -6.9 ( 17.69 )
        CD45+3+8-4+CCR6+CXCR3+38+DR+,12-Week FU,n=5,18|
    11.5 ( 16.47 )
    -18.7 ( 8.66 )
        CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 1, n=7, 23|
    -17.0 ( 6.80 )
    -10.5 ( 3.62 )
        CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 4, n=7, 21|
    14.2 ( 15.65 )
    12.2 ( 9.10 )
        CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 12, n=5, 22|
    3.4 ( 16.09 )
    -3.0 ( 7.55 )
        CD45+3+8-4+CCR6+CXCR3-38+DR+, 12-Week FU, n=5, 18|
    8.9 ( 12.29 )
    3.3 ( 6.36 )
        CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 1, n=7, 23|
    -73.2 ( 82.46 )
    -129.2 ( 46.04 )
        CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 4, n=7, 21|
    -159.6 ( 60.51 )
    -108.0 ( 35.05 )
        CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 12, n=5, 22|
    219.2 ( 299.65 )
    77.7 ( 146.73 )
        CD45+3+8-4+CCR6-CXCR3+38+DR+, 12-Week FU, n=5, 18|
    33.9 ( 66.09 )
    -104.0 ( 34.73 )
        CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 1, n=7, 23|
    -70.9 ( 25.90 )
    -70.5 ( 14.03 )
        CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 4, n=7, 21|
    -38.9 ( 30.69 )
    -56.3 ( 17.93 )
        CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 12, n=5, 22|
    -16.4 ( 198.13 )
    43.0 ( 92.38 )
        CD45+3+8-4+CCR6-CXCR3-38+DR+, 12-Week FU, n=5, 18|
    -12.7 ( 33.50 )
    -59.9 ( 17.32 )
        CD45+CD3+CD8-CD4+, Week 1, n=7, 23|
    -3845.3 ( 2648.60 )
    -163.0 ( 1444.61 )
        CD45+CD3+CD8-CD4+, Week 4, n=7, 21|
    1622.8 ( 2973.60 )
    1075.1 ( 1723.09 )
        vCD45+CD3+CD8-CD4+, Week 12, n=5, 22|
    2112.9 ( 4211.63 )
    1006.9 ( 2026.47 )
        CD45+CD3+CD8-CD4+, 12-Week FU, n=5, 18|
    1799.0 ( 2589.05 )
    -1832.0 ( 1366.65 )
        CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 1, n=7, 23|
    -514.6 ( 647.85 )
    -1030.2 ( 345.07 )
        CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 4, n=7, 21|
    -116.6 ( 757.58 )
    -316.5 ( 438.76 )
        CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 12, n=5, 22|
    -252.9 ( 827.53 )
    -506.4 ( 389.97 )
        CD45+CD3+CD8-CD4+CCR6+CXCR3+, 12-Week FU, n=5, 18|
    -688.1 ( 792.26 )
    -463.0 ( 412.22 )
        CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 1, n=7, 23|
    -817.1 ( 393.10 )
    -654.5 ( 212.18 )
        CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 4, n=7, 21|
    197.7 ( 475.88 )
    14.2 ( 277.06 )
        CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 12, n=5, 22|
    48.8 ( 541.14 )
    -219.7 ( 253.92 )
        CD45+CD3+CD8-CD4+CCR6+CXCR3-, 12-Week FU, n=5, 18|
    -311.6 ( 553.32 )
    -509.2 ( 291.09 )
        CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 1, n=7, 23|
    371.8 ( 1026.17 )
    1521.8 ( 547.18 )
        CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 4, n=7, 21|
    -24.5 ( 1678.23 )
    -292.5 ( 967.00 )
        CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 12, n=5, 22|
    2790.5 ( 2510.67 )
    1443.1 ( 1209.66 )
        CD45+CD3+CD8-CD4+CCR6-CXCR3+, 12-Week FU, n=5, 18|
    2295.9 ( 1787.02 )
    607.0 ( 927.11 )
        CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 1, n=7, 23|
    -3231.4 ( 2162.58 )
    45.4 ( 1187.37 )
        CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 4, n=7, 21|
    2084.9 ( 2873.95 )
    1637.6 ( 1665.46 )
        CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 12, n=5, 22|
    -1273.9 ( 2413.90 )
    161.4 ( 1209.82 )
        CD45+CD3+CD8-CD4+CCR6-CXCR3-, 12-Week FU, n=5, 18|
    -106.6 ( 1690.64 )
    -1316.7 ( 892.55 )
    Notes
    [23] - ITT Population
    [24] - ITT Population
    Statistical analysis title
    		 CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.35
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    14.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.9
         upper limit
    		 46.1
    Statistical analysis title
    		 CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.697
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    8.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.3
         upper limit
    		 52
    Statistical analysis title
    		 CD45+3+8-4+CCR6+CXCR3+38+DR+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.249
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -49.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -135.2
         upper limit
    		 36.8
    Statistical analysis title
    		 CD45+3+8-4+CCR6+CXCR3+38+DR+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.119
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -30.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -68.6
         upper limit
    		 8.3
    Statistical analysis title
    		 CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.403
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    6.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.3
         upper limit
    		 22.4
    Statistical analysis title
    		 CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.91
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -39.4
         upper limit
    		 35.2
    Statistical analysis title
    		 CD45+3+8-4+CCR6+CXCR3-38+DR+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.718
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -6.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -43.1
         upper limit
    		 30.1
    Statistical analysis title
    		 CD45+3+8-4+CCR6+CXCR3-38+DR+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.687
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -5.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -34.4
         upper limit
    		 23
    Statistical analysis title
    		 CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.559
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -249.8
         upper limit
    		 137.7
    Statistical analysis title
    		 CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.47
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    51.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -93.9
         upper limit
    		 197
    Statistical analysis title
    		 CD45+3+8-4+CCR6-CXCR3+38+DR+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.675
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -141.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -829.2
         upper limit
    		 546.3
    Statistical analysis title
    		 CD45+3+8-4+CCR6-CXCR3+38+DR+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.08
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -137.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -294
         upper limit
    		 18.2
    Statistical analysis title
    		 CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.989
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -60.5
         upper limit
    		 61.3
    Statistical analysis title
    		 CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.634
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -17.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -94.3
         upper limit
    		 59.6
    Statistical analysis title
    		 CD45+3+8-4+CCR6-CXCR3-38+DR+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.789
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    59.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -395.2
         upper limit
    		 513.9
    Statistical analysis title
    		 CD45+3+8-4+CCR6-CXCR3-38+DR+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.249
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -47.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -135.5
         upper limit
    		 41
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.234
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    3682.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2511.9
         upper limit
    		 9876.5
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.875
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -547.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7612.6
         upper limit
    		 6517.3
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.815
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1106
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10706
         upper limit
    		 8494.1
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.23
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3631
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9738.9
         upper limit
    		 2476.8
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.489
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -515.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2021.4
         upper limit
    		 990.1
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.822
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -199.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2001.7
         upper limit
    		 1602
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6+CXCR3+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.784
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -253.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2136.7
         upper limit
    		 1629.7
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6+CXCR3+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.804
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    225.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1633.1
         upper limit
    		 2083.2
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.719
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    162.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -754.5
         upper limit
    		 1079.9
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.742
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -183.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1317.4
         upper limit
    		 950.3
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6+CXCR3-, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.658
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -268.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1507.5
         upper limit
    		 970.5
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6+CXCR3-, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.755
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -197.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1499.3
         upper limit
    		 1104.2
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.333
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    1150
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1250
         upper limit
    		 3550
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.891
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -268
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4269.2
         upper limit
    		 3733.3
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6-CXCR3+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.633
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1347.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7073.1
         upper limit
    		 4378.3
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6-CXCR3+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.41
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1688.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5864.1
         upper limit
    		 2486.2
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.196
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    3276.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1786
         upper limit
    		 8339.6
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.894
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -447.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7285.5
         upper limit
    		 6390.8
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6-CXCR3-, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    1435.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4101.4
         upper limit
    		 6972
    Statistical analysis title
    		 CD45+CD3+CD8-CD4+CCR6-CXCR3-, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.534
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1210.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5213.1
         upper limit
    		 2792.7

    Primary: Change from Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+

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    End point title
    		 Change from Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16-, CD14lo+CD16br+
    End point description
    Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16- and CD14lo+CD16br+. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for CD14-HLA-DR+CD11cbr+CD123-, CD14br+CD16+, CD14br+CD16- and CD14lo+CD16br+ (10^3/Liter) baseline value, treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [25]
    28 [26]
    Units: 10^3 cells/Liter
    least squares mean (standard error)
        CD14-HLA-DR+CD11cbr+CD123-, Week 1, n=5, 18|
    -2017.6 ( 2452.91 )
    738.7 ( 1266.25 )
        CD14-HLA-DR+CD11cbr+CD123-, Week 4, n=6, 22|
    2766.3 ( 3220.54 )
    2278.8 ( 1696.12 )
        CD14-HLA-DR+CD11cbr+CD123-, Week 12, n=5, 21|
    5730.4 ( 5085.86 )
    5453.0 ( 2399.11 )
        CD14-HLA-DR+CD11cbr+CD123-, 12-Week FU, n=5, 18|
    5785.6 ( 5081.59 )
    5474.0 ( 2439.59 )
        CD14br+CD16+, Week 1, n=5, 18|
    -5376.0 ( 4748.95 )
    1491.0 ( 2452.69 )
        CD14br+CD16+, Week 4, n=6, 22|
    -5635.3 ( 5971.99 )
    2724.3 ( 3117.17 )
        CD14br+CD16+, Week 12, n=5, 21|
    25351.6 ( 9433.73 )
    2668.0 ( 4589.28 )
        CD14br+CD16+, 12-Week FU, n=5, 18|
    8557.2 ( 9914.93 )
    4800.0 ( 5266.23 )
        CD14br+CD16-, Week 1, n=5, 18|
    40079.7 ( 40456.86 )
    17662.7 ( 21211.91 )
        CD14br+CD16-, Week 4, n=6, 22|
    -17173.8 ( 24181.15 )
    10485.9 ( 12635.98 )
        CD14br+CD16-, Week 12, n=5, 21|
    -2981.8 ( 37788.70 )
    13201.2 ( 18684.22 )
        CD14br+CD16-, 12-Week FU, n=5, 18|
    31906.6 ( 45766.70 )
    -31512.8 ( 24027.16 )
        CD14lo+CD16br+, Week 1, n=5, 18|
    11248.2 ( 6598.36 )
    4334.6 ( 3466.71 )
        CD14lo+CD16br+, Week 4, n=6, 22|
    2522.9 ( 3757.96 )
    291.3 ( 1959.54 )
        CD14lo+CD16br+, Week 12, n=5, 21|
    10938.4 ( 5088.36 )
    759.2 ( 2534.27 )
        CD14lo+CD16br+, 12-Week FU, n=5, 18|
    24737.0 ( 7758.65 )
    3992.8 ( 4134.52 )
    Notes
    [25] - ITT Population
    [26] - ITT Population
    Statistical analysis title
    		 CD14-HLA-DR+CD11cbr+CD123-, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.328
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    2756.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2953.7
         upper limit
    		 8466.3
    Statistical analysis title
    		 CD14-HLA-DR+CD11cbr+CD123-, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.895
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -487.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8003.7
         upper limit
    		 7028.6
    Statistical analysis title
    		 CD14-HLA-DR+CD11cbr+CD123-, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.961
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -277.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12001
         upper limit
    		 11446.2
    Statistical analysis title
    		 CD14-HLA-DR+CD11cbr+CD123-, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.956
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -311.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11960.5
         upper limit
    		 11337.4
    Statistical analysis title
    		 CD14br+CD16+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.212
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    6866.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4230.7
         upper limit
    		 17964.6
    Statistical analysis title
    		 CD14br+CD16+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.227
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    8359.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5533.3
         upper limit
    		 22252.5
    Statistical analysis title
    		 CD14br+CD16+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.04
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -22683.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -44298.5
         upper limit
    		 -1068.8
    Statistical analysis title
    		 CD14br+CD16+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.741
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3757.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27146
         upper limit
    		 19631.6
    Statistical analysis title
    		 CD14br+CD16-, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.628
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -22417
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -116678
         upper limit
    		 71843.8
    Statistical analysis title
    		 CD14br+CD16-, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.321
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    27659.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28567.8
         upper limit
    		 83887.1
    Statistical analysis title
    		 CD14br+CD16-, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.704
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    16182.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -70377
         upper limit
    		 102742.9
    Statistical analysis title
    		 CD14br+CD16-, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.232
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -63419
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -170365
         upper limit
    		 43526.1
    Statistical analysis title
    		 CD14lo+CD16br+, Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.366
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -6913.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22588.4
         upper limit
    		 8761.1
    Statistical analysis title
    		 CD14lo+CD16br+, Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.603
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2231.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10976.8
         upper limit
    		 6513.6
    Statistical analysis title
    		 CD14lo+CD16br+, Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.084
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -10179.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21827.4
         upper limit
    		 1469.2
    Statistical analysis title
    		 CD14lo+CD16br+, 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.026
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -20744.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38771.8
         upper limit
    		 -2716.5

    Primary: Change from Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+

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    End point title
    		 Change from Baseline in Flow Cytometry: CD16+ Monocyte Panel: CD14-CD16+CD66b+
    End point description
    Whole blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Flow cytometry assessment included assessment of CD14-CD16+CD66b+ cell. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for CD14-CD16+CD66b+ (10^6/Liter) baseline value, treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [27]
    28 [28]
    Units: 10^6 cells/Liter
    least squares mean (standard error)
        Week 1, n=5, 19|
    -559.0 ( 269.84 )
    -380.9 ( 137.31 )
        Week 4, n=6, 22|
    -581.9 ( 377.03 )
    -41.5 ( 196.72 )
        Week 12, n=5, 21|
    -125.9 ( 460.53 )
    -378.6 ( 229.47 )
        12-Week FU, n=5, 18|
    -240.9 ( 430.65 )
    -199.3 ( 219.73 )
    Notes
    [27] - ITT Population
    [28] - ITT Population
    Statistical analysis title
    		 Week 1
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.564
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    178.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -448.3
         upper limit
    		 804.6
    Statistical analysis title
    		 Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.216
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    540.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -335.7
         upper limit
    		 1416.5
    Statistical analysis title
    		 Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.629
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -252.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1326
         upper limit
    		 820.8
    Statistical analysis title
    		 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.932
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    41.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -962.2
         upper limit
    		 1045.5

    Primary: Change from Baseline in Complement Biomarkers: Complement component 3 (C3), Complement component 4 (C4)

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    End point title
    		 Change from Baseline in Complement Biomarkers: Complement component 3 (C3), Complement component 4 (C4) [29]
    End point description
    Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Complement biomarkers included analysis of Complement C3 and Complement C4. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
    Notes
    [29] - 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: There are no statistical data to report
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [30]
    28 [31]
    Units: Ratio of complement biomarker
    geometric mean (geometric coefficient of variation)
        Complement C3, Week 1, n=9, 25|
    0.967 ( 7.43 )
    0.982 ( 11.76 )
        Complement C3, Week 2, n=8, 26|
    0.957 ( 11.72 )
    0.963 ( 14.15 )
        Complement C3, Week 4, n=9, 27|
    1.045 ( 18.42 )
    0.959 ( 12.62 )
        Complement C3, Week 6, n=7, 27|
    1.060 ( 12.00 )
    0.991 ( 11.71 )
        Complement C3, Week 8, n=7, 25|
    1.021 ( 12.54 )
    1.009 ( 10.85 )
        Complement C3, Week 12, n=7 24|
    0.988 ( 9.37 )
    1.003 ( 11.34 )
        Complement C3, 12-Week FU, n=7, 22|
    1.005 ( 19.15 )
    0.995 ( 10.65 )
        Complement C4, Week 1, n=9, 25|
    1.005 ( 11.40 )
    0.969 ( 13.13 )
        Complement C4, Week 2, n=8, 26|
    0.949 ( 9.64 )
    0.984 ( 16.45 )
        Complement C4, Week 4, n=9, 27|
    0.999 ( 12.06 )
    0.945 ( 14.63 )
        Complement C4, Week 6, n=7, 27|
    0.990 ( 10.31 )
    0.985 ( 17.32 )
        Complement C4, Week 8, n=7, 25|
    0.979 ( 7.66 )
    1.006 ( 13.53 )
        Complement C4, Week 12, n=7, 24|
    0.942 ( 15.57 )
    0.994 ( 12.75 )
        Complement C4, 12-Week FU, n=7, 22|
    0.982 ( 12.88 )
    0.986 ( 14.72 )
    Notes
    [30] - ITT Population
    [31] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in Complement Biomarkers: Complement component 4a (C4a), Complement component 5a (C5a), Complement Split Factor SC5b-9, Soluble cluster of differentiation 163 (sCD163)

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    End point title
    		 Change from Baseline in Complement Biomarkers: Complement component 4a (C4a), Complement component 5a (C5a), Complement Split Factor SC5b-9, Soluble cluster of differentiation 163 (sCD163) [32]
    End point description
    Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Complement biomarkers included analysis of Complement C4a, Complement C5a, Complement Split Factor SC5b-9 and Soluble CD163. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
    Notes
    [32] - 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: There are no statistical data to report
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [33]
    28 [34]
    Units: Ratio of complement biomarker
    geometric mean (geometric coefficient of variation)
        Complement C4a, Week 1, n=9, 27|
    1.159 ( 115.81 )
    0.990 ( 67.63 )
        Complement C4a, Week 2, n=8, 26|
    0.881 ( 55.58 )
    1.156 ( 75.77 )
        Complement C4a, Week 4, n=9, 27|
    0.840 ( 40.85 )
    1.100 ( 46.87 )
        Complement C4a, Week 6, n=7, 27|
    0.914 ( 66.71 )
    0.860 ( 53.87 )
        Complement C4a, Week 8, n=7, 25|
    1.017 ( 44.16 )
    0.998 ( 60.41 )
        Complement C4a, Week 12, n=7, 24|
    0.927 ( 58.05 )
    0.901 ( 93.48 )
        Complement C4a, 12-Week FU, n=7, 21|
    1.104 ( 40.27 )
    1.221 ( 56.53 )
        Complement C5a, Week 1, n=9, 27|
    0.927 ( 19.42 )
    0.991 ( 29.67 )
        Complement C5a, Week 2, n=8, 26|
    1.154 ( 36.82 )
    1.015 ( 55.60 )
        Complement C5a, Week 4, n=9, 27|
    0.943 ( 16.76 )
    1.010 ( 35.63 )
        Complement C5a, Week 6, n=7, 27|
    1.139 ( 61.77 )
    1.044 ( 33.94 )
        Complement C5a, Week 8, n=7, 25|
    0.980 ( 13.71 )
    0.957 ( 26.95 )
        Complement C5a, Week 12, n=7, 24|
    1.012 ( 8.41 )
    0.995 ( 29.49 )
        Complement C5a, 12-Week FU, n=7, 22|
    1.152 ( 42.75 )
    1.130 ( 32.16 )
        Complement Split Factor SC5b-9, Week 1, n=9, 27|
    0.971 ( 37.46 )
    1.020 ( 43.70 )
        Complement Split Factor SC5b-9, Week 2, n=8, 26|
    1.078 ( 28.80 )
    1.040 ( 60.64 )
        Complement Split Factor SC5b-9, Week 4, n=9, 27|
    0.930 ( 43.01 )
    1.126 ( 41.04 )
        Complement Split Factor SC5b-9, Week 6, n=7, 27|
    0.989 ( 23.18 )
    1.084 ( 53.90 )
        Complement Split Factor SC5b-9, Week 8, n=7, 25|
    0.889 ( 35.48 )
    1.055 ( 67.53 )
        Complement Split Factor SC5b-9, Week 12, n=7, 24|
    0.883 ( 30.26 )
    0.843 ( 72.14 )
        Complement Split Factor SC5b-9,12-Week FU,n=7, 22|
    1.039 ( 69.05 )
    1.041 ( 38.60 )
        sCD163, Week 1, n=9, 27|
    0.993 ( 24.28 )
    0.963 ( 16.38 )
        sCD163, Week 2, n=8, 26|
    1.101 ( 17.80 )
    0.954 ( 17.14 )
        sCD163, Week 4, n=9, 27|
    0.986 ( 15.89 )
    0.947 ( 27.10 )
        sCD163, Week 6, n=7, 27|
    0.938 ( 20.83 )
    0.959 ( 30.14 )
        sCD163, Week 8, n=7, 25|
    0.938 ( 30.03 )
    0.950 ( 28.73 )
        sCD163, Week 12, n=7, 24|
    0.937 ( 24.86 )
    0.915 ( 35.29 )
        sCD163, 12-Week FU, n=7, 21|
    1.200 ( 32.94 )
    0.994 ( 28.84 )
    Notes
    [33] - ITT Population
    [34] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in Mechanistic Biomarkers

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    End point title
    		 Change from Baseline in Mechanistic Biomarkers [35]
    End point description
    Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Mechanistic biomarkers included analysis of Interleukin 1 Beta, Interleukin 10, Interleukin 15, Interleukin 17 Alpha, Interleukin 17F, Interleukin 8 and Tumor Necrosis Factor. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. 99999 indicates that data is not available since 100% of the data was below limit of quantification at all time points. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 6, 8, 12, 12-Week FU (Week 22)
    Notes
    [35] - 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: There are no statistical data to report
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [36]
    28 [37]
    Units: Ratio of mechanistic biomarker
    geometric mean (geometric coefficient of variation)
        Interleukin 1 Beta, Week 1, n=9, 26|
    1.000 ( 99999 )
    1.000 ( 99999 )
        Interleukin 1 Beta, Week 2, n=8, 26|
    1.000 ( 99999 )
    1.000 ( 99999 )
        Interleukin 1 Beta, Week 4, n=9, 27|
    1.000 ( 99999 )
    1.000 ( 99999 )
        Interleukin 1 Beta, Week 6, n=7, 27|
    1.000 ( 99999 )
    1.000 ( 99999 )
        Interleukin 1 Beta, Week 8, n=7, 25|
    1.000 ( 99999 )
    1.000 ( 99999 )
        Interleukin 1 Beta, Week 12, n=7, 24|
    1.000 ( 99999 )
    1.000 ( 99999 )
        Interleukin 1 Beta, 12-Week FU, n=7, 21|
    1.000 ( 99999 )
    1.000 ( 99999 )
        Interleukin 10, Week 1, n=9, 26|
    0.962 ( 11.55 )
    0.994 ( 28.47 )
        Interleukin 10, Week 2, n=8, 26|
    1.206 ( 45.35 )
    1.048 ( 37.27 )
        Interleukin 10, Week 4, n=9, 27|
    0.875 ( 41.69 )
    0.985 ( 32.52 )
        Interleukin 10, Week 6, n=7, 27|
    0.842 ( 47.84 )
    0.960 ( 17.66 )
        Interleukin 10, Week 8, n=7, 25|
    1.197 ( 50.41 )
    0.969 ( 30.23 )
        Interleukin 10, Week 12, n=7, 24|
    0.842 ( 47.84 )
    0.989 ( 21.36 )
        Interleukin 10, 12-Week FU, n=7, 21|
    0.842 ( 47.84 )
    1.230 ( 62.91 )
        Interleukin 15, Week 1, n=9, 27|
    1.001 ( 12.70 )
    0.950 ( 59.23 )
        Interleukin 15, Week 2, n=8, 26|
    0.882 ( 41.99 )
    0.849 ( 102.76 )
        Interleukin 15, Week 4, n=9, 27|
    1.206 ( 47.87 )
    0.831 ( 84.07 )
        Interleukin 15, Week 6, n=7, 27|
    1.297 ( 48.81 )
    0.904 ( 90.53 )
        Interleukin 15, Week 8, n=7, 25|
    0.871 ( 37.95 )
    0.865 ( 90.30 )
        Interleukin 15, Week 12, n=7, 24|
    0.871 ( 37.95 )
    0.771 ( 82.21 )
        Interleukin 15, 12-Week FU, n=7, 21|
    0.871 ( 37.95 )
    0.636 ( 111.86 )
        Interleukin 17 Alpha, Week 1, n=9, 25|
    0.806 ( 53.03 )
    1.054 ( 93.04 )
        Interleukin 17 Alpha, Week 2, n=8, 25|
    0.935 ( 75.58 )
    0.942 ( 72.24 )
        Interleukin 17 Alpha, Week 4, n=9, 26|
    0.995 ( 91.45 )
    0.911 ( 102.66 )
        Interleukin 17 Alpha, Week 6, n=7, 26|
    1.015 ( 76.60 )
    0.867 ( 90.15 )
        Interleukin 17 Alpha, Week 8, n=7, 23|
    0.905 ( 77.24 )
    1.005 ( 135.76 )
        Interleukin 17 Alpha, Week 12, n=7, 23|
    1.007 ( 87.84 )
    0.857 ( 101.45 )
        Interleukin 17 Alpha, 12-Week FU, n=7, 20|
    0.969 ( 155.67 )
    0.999 ( 150.12 )
        Interleukin 17F, Week 1, n=9, 25|
    1.153 ( 36.21 )
    0.797 ( 78.96 )
        Interleukin 17F, Week 2, n=8, 26|
    1.062 ( 74.38 )
    0.911 ( 72.36 )
        Interleukin 17F, Week 4, n=9, 26|
    0.966 ( 21.09 )
    0.948 ( 89.47 )
        Interleukin 17F, Week 6, n=7, 25|
    0.787 ( 32.55 )
    1.013 ( 107.49 )
        Interleukin 17F, Week 8, n=7, 25|
    0.947 ( 19.20 )
    0.815 ( 91.93 )
        Interleukin 17F, Week 12, n=7, 23|
    1.002 ( 74.09 )
    0.884 ( 100.03 )
        Interleukin 17F, 12-Week FU, n=7, 21|
    1.130 ( 101.51 )
    0.741 ( 90.62 )
        Interleukin 8, Week 1, n=9, 26|
    1.104 ( 40.98 )
    1.081 ( 74.78 )
        Interleukin 8, Week 2, n=8, 26|
    1.505 ( 43.78 )
    0.861 ( 78.64 )
        Interleukin 8, Week 4, n=9, 27|
    1.102 ( 38.30 )
    0.773 ( 82.48 )
        Interleukin 8, Week 6, n=7, 27|
    1.229 ( 61.82 )
    0.720 ( 72.70 )
        Interleukin 8, Week 8, n=7, 25|
    1.547 ( 53.88 )
    0.761 ( 80.51 )
        Interleukin 8, Week 12, n=7, 24|
    1.240 ( 49.03 )
    0.850 ( 80.98 )
        Interleukin 8, 12-Week FU, n=7, 21|
    1.191 ( 42.58 )
    0.841 ( 96.92 )
        Tumor Necrosis Factor, Week 1, n=9, 26|
    0.976 ( 15.20 )
    0.994 ( 18.45 )
        Tumor Necrosis Factor, Week 2, n=8, 26|
    0.951 ( 19.84 )
    0.977 ( 16.81 )
        Tumor Necrosis Factor, Week 4, n=9, 27|
    0.933 ( 17.70 )
    0.871 ( 48.19 )
        Tumor Necrosis Factor, Week 6, n=7, 27|
    1.087 ( 36.81 )
    0.929 ( 21.48 )
        Tumor Necrosis Factor, Week 8, n=7, 25|
    1.110 ( 25.33 )
    0.930 ( 20.85 )
        Tumor Necrosis Factor, Week 12, n=7, 24|
    1.021 ( 38.53 )
    0.969 ( 29.74 )
        Tumor Necrosis Factor,12-Week FU, n=7, 21|
    1.619 ( 180.16 )
    1.057 ( 34.72 )
    Notes
    [36] - ITT Population
    [37] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D

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    End point title
    		 Change from Baseline in Safety Biomarkers: 3B-Cholestenoic Acid, Surfactant Protein D [38]
    End point description
    Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Safety biomarkers included analysis of 3B-Cholestenoic Acid and Surfactant Protein D. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Week 12, 12-Week FU (Week 22)
    Notes
    [38] - 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: There are no statistical data to report
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [39]
    28 [40]
    Units: Ratio of safety biomarker
    geometric mean (geometric coefficient of variation)
        3B-Cholestenoic Acid, Week 12, n=7, 24|
    1.012 ( 16.52 )
    1.094 ( 19.45 )
        3B-Cholestenoic Acid, Week 22, n=7, 22|
    1.020 ( 20.25 )
    1.009 ( 22.67 )
        Surfactant Protein D, Week 12, n=7, 24|
    1.003 ( 23.10 )
    1.134 ( 27.96 )
        Surfactant Protein D, 12-Week FU, n=7, 21|
    1.140 ( 45.71 )
    0.985 ( 31.32 )
    Notes
    [39] - ITT Population
    [40] - ITT Population
    No statistical analyses for this end point

    Primary: Change from Baseline in Safety Biomarkers: KL-6 Antigen

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    End point title
    		 Change from Baseline in Safety Biomarkers: KL-6 Antigen [41]
    End point description
    Blood samples were collected and analyzed for markers which may be predictive of rheumatoid arthritis disease activity. Safety biomarker included analysis of KL-6 Antigen. Baseline was defined at Day 1. Change from Baseline was calculated as ratio of Baseline value to post-dose value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline and Week 12, 12-Week FU (Week 22)
    Notes
    [41] - 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: There are no statistical data to report
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [42]
    28 [43]
    Units: Ratio of safety biomarker
    geometric mean (geometric coefficient of variation)
        Week 12, n=6, 24|
    1.416 ( 220.58 )
    1.099 ( 66.17 )
        12-Week FU, n=6, 21|
    0.937 ( 62.43 )
    1.024 ( 93.56 )
    Notes
    [42] - ITT Population
    [43] - ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI)

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    End point title
    		 Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI)
    End point description
    An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect and associated with liver injury and impaired liver function. An AESI include serious infections, opportunistic infections, neutropenia, respiratory events, pulmonary alveolar proteinosis, hypersensitivity reactions, injection site reactions, persistent cough or dyspnea.
    End point type
    Secondary
    End point timeframe
    Up to 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [44]
    28 [45]
    Units: Participants
        Any AEs|
    4
    11
        Any SAEs|
    0
    0
        AESI|
    0
    1
    Notes
    [44] - ITT Population
    [45] - ITT Population
    No statistical analyses for this end point

    Secondary: Number of participants who tested positive for Anti-GSK3196165 Binding Antibody Detection at any time post-Baseline

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    End point title
    		 Number of participants who tested positive for Anti-GSK3196165 Binding Antibody Detection at any time post-Baseline
    End point description
    Immunogenicity samples for determination of anti-drug-antibody (ADA) were collected. The presence of treatment emergent ADA was determined using a GSK3196165 bridging style ADA assay with a bio-analytically determined cut point determined during assay validation. Samples taken after dosing with GSK3196165 that had a value at or above the cut-point was considered potentially treatment-emergent ADA-positive. The immunogenicity population consisted of all participants in the ITT population, who had at least one valid immunogenicity assessment.
    End point type
    Secondary
    End point timeframe
    Up to 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [46]
    28 [47]
    Units: Participants
    0
    0
    Notes
    [46] - Immunogenicity Population
    [47] - Immunogenicity Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in synovitis as assessed by Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis magnetic resonance imaging scoring system (RAMRIS) in the most affected hand/wrist

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    End point title
    		 Change from Baseline in synovitis as assessed by Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis magnetic resonance imaging scoring system (RAMRIS) in the most affected hand/wrist
    End point description
    For synovitis a total of 8 joints were evaluated. Individual joint scores range from 0-3, where 0= normal, 1=mild, 2=moderate and 3=severe. The final synovitis score is the sum of the individual joint scores. Total score range from 0 (best) to 24 (worst). If an individual location is scored either ‘Not Visible’ or ‘Surgically Modified’ then the score for that location was set to missing. Missing joint scores was imputed as the mean of the non-missing joint scores. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Repeated measures analysis adjusted for synovitis score baseline value, treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Data has been presented for Median and 95% credible interval. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [48]
    28 [49]
    Units: Scores on a scale
    median (confidence interval 95%)
        Week 4, n=6, 12|
    0.05 (-1.92 to 1.95)
    -0.07 (-1.19 to 1.12)
        Week 12, n=5, 21|
    0.84 (-1.57 to 3.12)
    -1.33 (-2.54 to -0.13)
        12-Week FU, n=7, 19|
    1.13 (-1.32 to 3.55)
    -1.13 (-2.47 to 0.20)
    Notes
    [48] - ITT Population
    [49] - ITT Population
    Statistical analysis title
    		 Week 4
    Statistical analysis description
    For Posterior Probability Difference <0
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.547
    Method
    		 Repeated Measures Bayesian Model
    Parameter type
    		 Median difference (net)
    Point estimate
    -0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.32
         upper limit
    		 2.23
    Statistical analysis title
    		 Week 12, For Posterior Probability Difference <0
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.948
    Method
    		 Repeated Measures Bayesian Model
    Parameter type
    		 Median difference (net)
    Point estimate
    -2.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.77
         upper limit
    		 0.51
    Statistical analysis title
    		 12-Week FU
    Statistical analysis description
    For Posterior Probability Difference <0
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.949
    Method
    		 Repeated Measures Bayesian Model
    Parameter type
    		 Median difference (net)
    Point estimate
    -2.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.02
         upper limit
    		 0.45
    Statistical analysis title
    		 Week 4, For Posterior Probability Difference >0
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.453
    Method
    		 Repeated Measures Bayesian Model
    Parameter type
    		 Median difference (net)
    Point estimate
    -0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.32
         upper limit
    		 2.23
    Statistical analysis title
    		 Week 12, For Posterior Probability Difference >0
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.052
    Method
    		 Repeated Measures Bayesian Model
    Parameter type
    		 Median difference (net)
    Point estimate
    -2.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.77
         upper limit
    		 0.51
    Statistical analysis title
    		 12-Week FU
    Statistical analysis description
    For Posterior Probability Difference >0
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.051
    Method
    		 Repeated Measures Bayesian Model
    Parameter type
    		 Median difference (net)
    Point estimate
    -2.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.02
         upper limit
    		 0.45

    Secondary: Change from Baseline in osteitis as assessed by OMERACT RAMRI scoring system in the most affected hand/wrist

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    End point title
    		 Change from Baseline in osteitis as assessed by OMERACT RAMRI scoring system in the most affected hand/wrist
    End point description
    For bone edema/osteitis a total of 25 locations was evaluated. Individual location scores ranged from 0-3, where, 0: no edema; 1: 1–33% of bone edematous; 2: 34–66% of bone edematous; 3: 67–100% of bone edematous. Final bone edema/osteitis score is sum of individual location scores. Total score ranged from 0 (best) to 75 (worst). Baseline was defined at Day 1. Change from Baseline was calculated by subtracting post-dose value from Baseline value. If an individual location was scored either ‘Not Visible’ or ‘Surgically Modified’ or ‘Not Assessable’ then the score for that location was set to be missing. Missing joint scores was imputed as mean of non-missing location scores. Repeated measures analysis adjusted for Bone Edema/Osteitis Score baseline value, treatment group, disease duration (<=2 or >2 years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [50]
    28 [51]
    Units: Scores on a scale
    least squares mean (standard error)
        Week 4, n=6, 12|
    -0.1 ( 0.11 )
    -0.1 ( 0.06 )
        Week 12, n=5, 21|
    0.0 ( 1.04 )
    -0.8 ( 0.56 )
        12-Week FU, n=7,19|
    0.5 ( 1.33 )
    -0.9 ( 0.74 )
    Notes
    [50] - ITT Population
    [51] - ITT Population
    Statistical analysis title
    		 Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.94
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.3
    Statistical analysis title
    		 Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.521
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.2
         upper limit
    		 1.6
    Statistical analysis title
    		 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.396
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 1.8

    Secondary: Change from Baseline in erosion as assessed by OMERACT RAMRI scoring system in the most affected hand/wrist

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    End point title
    		 Change from Baseline in erosion as assessed by OMERACT RAMRI scoring system in the most affected hand/wrist
    End point description
    For bone erosion a total of 25 locations were evaluated. Individual location scores range from 0-10, where, 0: no erosion; 1: 1–10% of bone eroded and 10: 91-100% of bone eroded. The final bone erosion score is the sum of the individual location scores. The total score ranged from 0 (best) to 250 (worst). If an individual location was scored either ‘Not Visible’ or ‘Surgically Modified’ or ‘Not Assessable’ then the score for that location was set to be missing. Missing joint scores was imputed as the mean of the non-missing location scores. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Analysis was performed using repeated measures analysis adjusted for Bone Erosion Score baseline value, treatment group, disease duration (<=2 or >2 years), visit and treatment group. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 12, 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [52]
    28 [53]
    Units: Scores on a scale
    least squares mean (standard error)
        Week 4, n=6, 12|
    0.2 ( 0.49 )
    0.3 ( 0.30 )
        Week 12, n=5, 21|
    0.8 ( 0.50 )
    0.4 ( 0.26 )
        12-Week FU, n=7, 19|
    1.5 ( 0.47 )
    0.5 ( 0.27 )
    Notes
    [52] - ITT Population
    [53] - ITT Population
    Statistical analysis title
    		 Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.945
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 1.2
    Statistical analysis title
    		 Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.475
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 0.7
    Statistical analysis title
    		 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.086
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 0.1

    Secondary: Change from Baseline in synovitis as assessed by rheumatoid arthritis MRI quantitative (RAMRIQ) assessment in the most affected hand/wrist

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    End point title
    		 Change from Baseline in synovitis as assessed by rheumatoid arthritis MRI quantitative (RAMRIQ) assessment in the most affected hand/wrist
    End point description
    RAMRIQ is an automated volume quantification assessment. RAMRIQ assessed same pathologies and joints (except metacarpophalangeal joint [MCP1]) as RAMRIS allowing for direct comparison of results obtained using the two methods. Bones were automatically identified in pre-contrast, coronal T1 images using active appearance modelling (AAMs). Joint capsules and soft tissues were also segmented with AAMs, providing consistent 3D regions of interest (ROI) for synovial enhancement across all time points. Synovial volume was calculated as voxels that enhance within each ROI. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Repeated measures analysis adjusted for Synovitis baseline value, treatment group, disease duration (<=2 or >2years), visit and treatment group by visit interaction. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 12 and 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [54]
    28 [55]
    Units: Milliliters
    least squares mean (standard error)
        Week 4, n=6, 12|
    34.1 ( 1052.52 )
    245.5 ( 776.24 )
        Week 12, n=5, 21|
    -912.3 ( 1405.77 )
    -1417.0 ( 671.54 )
        12-Week FU, n=7, 19|
    364.0 ( 1372.20 )
    -1172.1 ( 844.13 )
    Notes
    [54] - ITT Population
    [55] - ITT Population
    Statistical analysis title
    		 Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.874
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    211.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2589.2
         upper limit
    		 3012
    Statistical analysis title
    		 Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.749
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -504.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3730.4
         upper limit
    		 2720.9
    Statistical analysis title
    		 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.352
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1536
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4884.2
         upper limit
    		 1812.1

    Secondary: Change from Baseline in osteitis as assessed by RAMRIQ assessment in the most affected hand/wrist

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    End point title
    		 Change from Baseline in osteitis as assessed by RAMRIQ assessment in the most affected hand/wrist
    End point description
    RAMRIQ is an automated volume quantification assessment for edema volume. RAMRIQ assessed the same pathologies and joints (except MCP1) as RAMRIS, allowing for direct comparison of results obtained using the two methods. Bones were automatically identified in pre-contrast, coronal T1 images using AAMs. Joint capsules and soft tissues were also segmented with AAMs, providing consistent 3D ROI for synovial enhancement across all time points. Edema volume was defined as non-erosion contrast-enhancing voxels inside the bone. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 12 and 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [56]
    28 [57]
    Units: Milliliters
    least squares mean (standard error)
        Week 4, n=6, 12|
    -0.0045 ( 0.0102 )
    0.0084 ( 0.0057 )
        Week 12, n=5, 21|
    -0.0045 ( 0.0035 )
    -0.0009 ( 0.0019 )
        12-Week FU, n=7, 19|
    -0.0038 ( 0.0016 )
    -0.0027 ( 0.0009 )
    Notes
    [56] - ITT Population
    [57] - ITT Population
    Statistical analysis title
    		 Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.291
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.0128
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0123
         upper limit
    		 0.038
    Statistical analysis title
    		 Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.375
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.0036
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0046
         upper limit
    		 0.0118
    Statistical analysis title
    		 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.588
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.001
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0028
         upper limit
    		 0.0049

    Secondary: Change from Baseline in erosion as assessed by RAMRIQ assessment in the most affected hand/wrist

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    End point title
    		 Change from Baseline in erosion as assessed by RAMRIQ assessment in the most affected hand/wrist
    End point description
    RAMRIQ is an automated volume quantification assessment for erosion volume. RAMRIQ assessed the same pathologies and joints (except MCP1) as RAMRIS, allowing for direct comparison of results obtained using the two methods. Bones were automatically identified in pre-contrast, coronal T1 images using AAMs. Joint capsules and soft tissues were also segmented with AAMs, providing consistent 3D ROI for synovial enhancement across all time points. Erosion volume was identified inside the bone surfaces using voxel-based classification. The volume of BME and erosions was normalised to total bone volume for statistical analysis. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post-dose value from the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 12 and 12-Week FU (Week 22)
    End point values
    		 Placebo GSK3196165 180 mg
    Number of subjects analysed
    11 [58]
    28 [59]
    Units: Milliliters
    least squares mean (standard error)
        Week 4, n=6, 12|
    0.0007 ( 0.0012 )
    0.0006 ( 0.0008 )
        Week 12, n=5, 21|
    0.0003 ( 0.0011 )
    -0.0000 ( 0.0006 )
        12-Week FU, n=7, 19|
    -0.0002 ( 0.0023 )
    0.0003 ( 0.0013 )
    Notes
    [58] - ITT Population
    [59] - ITT Population
    Statistical analysis title
    		 Week 4
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.915
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.0002
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0033
         upper limit
    		 0.0029
    Statistical analysis title
    		 Week 12
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.771
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.0004
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0028
         upper limit
    		 0.0021
    Statistical analysis title
    		 12-Week FU
    Comparison groups
    Placebo v GSK3196165 180 mg
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.85
    Method
    		 Repeated measures analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.0005
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0048
         upper limit
    		 0.0058

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs and SAEs were collected from start of study treatment up to 12-Week FU (Week 22)
    Adverse event reporting additional description
    ITT Population was used for the analysis of safety data.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    GSK3196165 180 mg
    Reporting group description
    		 Eligible participants received GSK3196165 180 mg SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to GSK3196165, participants also received MTX 7.5–5 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.

    Reporting group title
    Placebo
    Reporting group description
    		 Eligible participants received matching placebo SC into thigh or abdomen once weekly for 5 weeks, and then every other week until Week 10. In addition to placebo, participants also received MTX 7.5–25 mg/week and folic (or folinic) acid >=5 mg/week during the combination treatment period.

    Serious adverse events
    		 GSK3196165 180 mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 11 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 GSK3196165 180 mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 28 (39.29%)
    4 / 11 (36.36%)
    Investigations
    Weight increased
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Tachycardia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 11 (0.00%)
         occurrences all number
    3
    0
    Asthma
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    Erythema
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Rosacea
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Seborrhoeic dermatitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Initial insomnia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    2
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    0
    2
    Musculoskeletal pain
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 11 (9.09%)
         occurrences all number
    1
    1
    Laryngitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Mar 2016
    This amendment includes classification of primary and secondary objectives and endpoints in Section 1 and Section 3; extension of the screening window to six weeks in Section 1, Section 4.1, Section 5.3.1, Section 7.1, and Section 7.2; correction of several typographical errors; clarification of likely numbers of participants screened in Section 4.3; correction of >15% relative decrease in DLCO as a trigger point in Section 4.6.1; clarification of DLCO testing in Section 5.1, Section 5.3.2.2, Section 7.1, Section 7.2, and Section 7.6.12; addition of Day 1 joint count and correction of mandatory chest HRCT if DLCO ≥60% - <70% predicted in Section 5.1; revision that participants must have passed all screening assessments (including laboratory tests) prior to undertaking MRI scanning, and that whole blood flow cytometry is scheduled on Day 1 in Section 7.1; an additional Exclusion Criterion for MRI in Section 5.2; correction that re-screening is permitted in Section 5.3.1; correction that RNA analysis is not part of the pharmacogenetics substudy in Section 7.1 and Section 7.2; clarification of the RA Symptom and Impact Diary in Section 7.5.2; clarification of PK sample in Section 7.2; clarification of MRI image processing in Section 7.9; clarification of abbreviations in Appendix 12.1; revision of contraception guidance in Appendix 12.2; and clarification of data recording in Appendix 12.7.

    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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