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    Clinical Trial Results:
    Study of safety and efficacy of multiple VAY736 doses in patients with moderate to severe primary Sjogren’s Syndrome (pSS)

    Summary
    EudraCT number
    		 2016-003292-22
    Trial protocol
    		 DE   ES   PT   GB   FR   NL   HU   BE   AT   PL   IT   RO  
    Global end of trial date
    23 Sep 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Oct 2022
    First version publication date
    11 Oct 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CVAY736A2201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02962895
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
    Scientific contact
    Study Director, Novartis Pharmaceuticals, 1 862 7788300, novartis.email@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    23 Sep 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Jun 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Sep 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate a dose response of VAY736 defined as change in ESSDAI from baseline at 24 weeks
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Jun 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 10
    Country: Number of subjects enrolled
    Austria: 10
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Chile: 9
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    Germany: 29
    Country: Number of subjects enrolled
    United Kingdom: 9
    Country: Number of subjects enrolled
    Hungary: 8
    Country: Number of subjects enrolled
    Israel: 3
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Japan: 12
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Poland: 10
    Country: Number of subjects enrolled
    Portugal: 9
    Country: Number of subjects enrolled
    Romania: 4
    Country: Number of subjects enrolled
    Russian Federation: 15
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    Taiwan: 7
    Country: Number of subjects enrolled
    United States: 31
    Worldwide total number of subjects
    190
    EEA total number of subjects
    94
    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)
    163
    From 65 to 84 years
    27
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 190 Patients were enrolled from 56 centers in 19 countries.

    Pre-assignment
    Screening details
    		 Period one was the screening period and is not shown here.

    Period 1
    Period 1 title
    Period 2 - Randomized Set
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Subject, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Placebo
    Arm description
    		 Placebo control
    Arm type
    		 Placebo

    Investigational medicinal product name
    PLACEBO
    Investigational medicinal product code
    PLACEBO
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    S.C.

    Arm title
    		 VAY736 5 mg
    Arm description
    		 VAY736 low
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736
    Investigational medicinal product code
    Other name
    ianalumab
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    5 mg s.c.

    Arm title
    		 VAY736 50 mg
    Arm description
    		 VAY736 medium
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736
    Investigational medicinal product code
    Other name
    ianalumab
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    50 mg s.c.

    Arm title
    		 VAY736 300 mg
    Arm description
    		 VAY736 high
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736
    Investigational medicinal product code
    Other name
    ianalumab
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    300 mg s.c.

    Number of subjects in period 1
    		Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Started
    49
    47
    47
    47
    Completed
    47
    42
    43
    46
    Not completed
    2
    5
    4
    1
         Consent withdrawn by subject
    1
    1
    2
    -
         New therapy for indication
    1
    -
    -
    -
         Adverse event, non-fatal
    -
    2
    2
    -
         Non-compliance with treatment
    -
    1
    -
    -
         Pregnancy
    -
    -
    -
    1
         Withdrawal of Informed Consent
    -
    1
    -
    -
    Period 2
    Period 2 title
    Period 3 - Randomized Set
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 VAY736 150 mg
    Arm description
    		 Placebo in Period 2 and VAY736 150 mg in Period 3
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736
    Investigational medicinal product code
    Other name
    ianalumab
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    150 mg s.c.

    Arm title
    		 VAY736 - Placebo 300 mg
    Arm description
    		 VAY736 300 mg in Period 2 and Placebo in Period 3
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736 300 mg - VAY736 300 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Injection
    Dosage and administration details
    VAY736 300 mg - VAY736 300 mg

    Arm title
    		 VAY736 300 mg - VAY736 300 mg
    Arm description
    		 VAY736 300 mg in Period 2 and Period 3
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736
    Investigational medicinal product code
    Other name
    300 mg vs 300 mg
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Any VAY736

    Number of subjects in period 2
    		VAY736 150 mg VAY736 - Placebo 300 mg VAY736 300 mg - VAY736 300 mg
    Started
    47
    22
    21
    Completed
    42
    22
    17
    Not completed
    5
    0
    4
         Adverse event, non-fatal
    5
    -
    2
         Pregnancy
    -
    -
    1
         Patient/guardian decision
    -
    -
    1
    Period 3
    Period 3 title
    Period 4
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Placebo
    Arm description
    		 Placebo control
    Arm type
    		 Placebo

    Investigational medicinal product name
    PLACEBO
    Investigational medicinal product code
    Other name
    PLACEBO
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    s.c.

    Arm title
    		 VAY736 5 mg
    Arm description
    		 VAY736 low
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736
    Investigational medicinal product code
    Other name
    ianalumab
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    5 mg s.c.

    Arm title
    		 VAY736 50 mg
    Arm description
    		 VAY736 medium
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736
    Investigational medicinal product code
    Other name
    ianalumab
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    50 mg s.c.

    Arm title
    		 VAY736 150 mg
    Arm description
    		 Placebo in Period 2 and VAY736 150 mg in Period 3
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736
    Investigational medicinal product code
    Other name
    ianalumab
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    150 mg s.c.

    Arm title
    		 VAY736 300 mg
    Arm description
    		 VAY736 high
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736
    Investigational medicinal product code
    Other name
    ianalumab
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    300 mg s.c.

    Arm title
    		 VAY736 - Placebo 300 mg
    Arm description
    		 VAY736 300 mg in Period 2 and Placebo in Period 3
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736 300 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Injection
    Dosage and administration details
    VAY736 300 mg

    Arm title
    		 VAY736 300 mg - VAY736 300 mg
    Arm description
    		 VAY736 300 mg in Period 2 and Period 3
    Arm type
    		 Experimental

    Investigational medicinal product name
    VAY736 300 mg - VAY736 300 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Injection
    Dosage and administration details
    VAY736 300 mg - VAY736 300 mg

    Investigational medicinal product name
    VAY736 300 mg - VAY736 300 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Injection
    Dosage and administration details
    VAY736 300 mg - VAY736 300 mg

    Number of subjects in period 3
    		Placebo VAY736 5 mg VAY736 50 mg VAY736 150 mg VAY736 300 mg VAY736 - Placebo 300 mg VAY736 300 mg - VAY736 300 mg
    Started
    2
    47
    47
    46
    4
    22
    20
    Completed
    2
    41
    43
    42
    1
    20
    20
    Not completed
    0
    6
    4
    4
    3
    2
    0
         Consent withdrawn by subject
    -
    2
    3
    2
    1
    2
    -
         New therapy for indication
    -
    -
    -
    1
    -
    -
    -
         Lost to follow-up
    -
    -
    -
    1
    -
    -
    -
         Withdrawal of Informed Consent
    -
    3
    1
    -
    2
    -
    -
         Lack of efficacy
    -
    1
    -
    -
    -
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo control

    Reporting group title
    VAY736 5 mg
    Reporting group description
    		 VAY736 low

    Reporting group title
    VAY736 50 mg
    Reporting group description
    		 VAY736 medium

    Reporting group title
    VAY736 300 mg
    Reporting group description
    		 VAY736 high

    Reporting group values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg Total
    Number of subjects
    		 49 47 47 47 190
    Age Categorical
    Randomized Set
    Units: Participants
        <=18 years
    		 0 0 0 0 0
        Between 18 and 65 years
    		 45 37 42 39 163
        >=65 years
    		 4 10 5 8 27
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 47.9 ( 12.44 ) 52.5 ( 13.64 ) 51.0 ( 11.12 ) 49.1 ( 15.41 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 47 46 41 46 180
        Male
    		 2 1 6 1 10
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    		 4 3 10 5 22
        Black or African American
    		 0 1 0 0 1
        White
    		 44 42 37 42 165
        Unknown
    		 1 1 0 0 2
    Subject analysis sets

    Subject analysis set title
    Placebo - VAY150 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo control

    Subject analysis set title
    VAY736 300 mg - Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    VAY736 high

    Subject analysis set title
    VAY736 300 mg - Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    VAY736 300 mg - Placebo

    Subject analysis sets values
    		 Placebo - VAY150 mg VAY736 300 mg - Placebo VAY736 300 mg - Placebo
    Number of subjects
    49
    26
    21
    Age Categorical
    Randomized Set
    Units: Participants
        <=18 years
    0
    0
    0
        Between 18 and 65 years
    0
    0
    0
        >=65 years
    0
    0
    0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    55.0 ( 15.053 )
    55.77 ( 20.407 )
    2.15 ( 1.47 )
    Sex: Female, Male
    Units: Participants
        Female
        Male
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
        Black or African American
        White
        Unknown

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo control

    Reporting group title
    VAY736 5 mg
    Reporting group description
    		 VAY736 low

    Reporting group title
    VAY736 50 mg
    Reporting group description
    		 VAY736 medium

    Reporting group title
    VAY736 300 mg
    Reporting group description
    		 VAY736 high
    Reporting group title
    VAY736 150 mg
    Reporting group description
    		 Placebo in Period 2 and VAY736 150 mg in Period 3

    Reporting group title
    VAY736 - Placebo 300 mg
    Reporting group description
    		 VAY736 300 mg in Period 2 and Placebo in Period 3

    Reporting group title
    VAY736 300 mg - VAY736 300 mg
    Reporting group description
    		 VAY736 300 mg in Period 2 and Period 3
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo control

    Reporting group title
    VAY736 5 mg
    Reporting group description
    		 VAY736 low

    Reporting group title
    VAY736 50 mg
    Reporting group description
    		 VAY736 medium

    Reporting group title
    VAY736 150 mg
    Reporting group description
    		 Placebo in Period 2 and VAY736 150 mg in Period 3

    Reporting group title
    VAY736 300 mg
    Reporting group description
    		 VAY736 high

    Reporting group title
    VAY736 - Placebo 300 mg
    Reporting group description
    		 VAY736 300 mg in Period 2 and Placebo in Period 3

    Reporting group title
    VAY736 300 mg - VAY736 300 mg
    Reporting group description
    		 VAY736 300 mg in Period 2 and Period 3

    Subject analysis set title
    Placebo - VAY150 mg
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo control

    Subject analysis set title
    VAY736 300 mg - Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    VAY736 high

    Subject analysis set title
    VAY736 300 mg - Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    VAY736 300 mg - Placebo

    Primary: Change from baseline in ESSDAI score at Week 24

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    End point title
    		 Change from baseline in ESSDAI score at Week 24
    End point description
    Dose response measured by change multi-dimensional disease activity as assessed by the physician. Score range is 0-123. Higher scores on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states A negative change from baseline indicates improvement in disease status.
    End point type
    Primary
    End point timeframe
    Baseline, 24 weeks
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: Scores on a scale
        least squares mean (standard error)
    -6.39 ( 0.808 )
    -5.64 ( 0.850 )
    -6.93 ( 0.836 )
    -8.30 ( 0.828 )
    Statistical analysis title
    		 VAY736 5 mg
    Comparison groups
    Placebo v VAY736 5 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5161
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.52
         upper limit
    		 3.02
    Statistical analysis title
    		 VAY736 300 mg
    Comparison groups
    Placebo v VAY736 300 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0921
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -1.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.15
         upper limit
    		 0.32
    Statistical analysis title
    		 VAY736 50 mg
    Comparison groups
    Placebo v VAY736 50 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6332
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    -0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 1.71

    Secondary: Change from baseline in ESSDAI score at Weeks 4, 8, 12, and 16

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    End point title
    		 Change from baseline in ESSDAI score at Weeks 4, 8, 12, and 16
    End point description
    Dose response measured by change multi-dimensional disease activity as assessed by the physician. Score range is 0-123. Higher scores on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states A negative change from baseline indicates improvement in disease status.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, and 16
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: Scores on a scale
    least squares mean (standard error)
        Week 4
    -3.73 ( 0.626 )
    -2.28 ( 0.661 )
    -3.37 ( 0.638 )
    -4.53 ( 0.651 )
        Week 8
    -4.13 ( 0.704 )
    -4.65 ( 0.733 )
    -4.73 ( 0.720 )
    -6.38 ( 0.717 )
        Week 12
    -5.45 ( 0.721 )
    -4.89 ( 0.762 )
    -5.69 ( 0.739 )
    -6.64 ( 0.739 )
        Week 16
    -6.08 ( 0.818 )
    -5.67 ( 0.852 )
    -6.17 ( 0.835 )
    -6.99 ( 0.836 )
    No statistical analyses for this end point

    Secondary: Change from baseline in ESSPRI score at Week 24

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    End point title
    		 Change from baseline in ESSPRI score at Week 24
    End point description
    Change in quality of life measure by patient reported outcome (PRO) The EULAR Sjörgen's Syndrome Patient Reported Index (ESSPRI) is an established disease outcome measure for Sjögren’s syndrome that is calculated by averaging the scales for pain, fatigue and dryness. The total score is the mean score of the 3 scales and ranges between 0 and 10 with higher values indicating more severity of symptoms. A negative change from baseline is a favourable outcome.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 weeks
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: Scores on a scale
        least squares mean (standard error)
    -1.71 ( 0.288 )
    -1.39 ( 0.304 )
    -1.70 ( 0.301 )
    -1.77 ( 0.295 )
    Statistical analysis title
    		 VAY736 5 mg
    Comparison groups
    Placebo v VAY736 5 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4457
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 1.13
    Statistical analysis title
    		 VAY736 50 mg
    Comparison groups
    Placebo v VAY736 50 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.301
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.79
         upper limit
    		 0.82
    Statistical analysis title
    		 VAY736 300 mg
    Comparison groups
    Placebo v VAY736 300 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8858
    Method
    		 Mixed models analysis
    Parameter type
    		 Least Square Mean Difference
    Point estimate
    -0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.86
         upper limit
    		 0.74

    Secondary: Change from baseline in ESSPRI score at Weeks 4, 8, 12 and 16

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    End point title
    		 Change from baseline in ESSPRI score at Weeks 4, 8, 12 and 16
    End point description
    Change in quality of life measure by patient reported outcome (PRO) The EULAR Sjörgen's Syndrome Patient Reported Index (ESSPRI) is an established disease outcome measure for Sjögren’s syndrome that is calculated by averaging the scales for pain, fatigue and dryness. The total score is the mean score of the 3 scales and ranges between 0 and 10 with higher values indicating more severity of symptoms. A negative change from baseline is a favourable outcome.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12 and 16
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: Scores on a scale
    least squares mean (standard error)
        Week 4
    -0.54 ( 0.236 )
    -0.67 ( 0.247 )
    -0.80 ( 0.241 )
    -0.88 ( 0.242 )
        Week 8
    -0.94 ( 0.242 )
    -0.84 ( 0.255 )
    -1.06 ( 0.251 )
    -1.8 ( 0.248 )
        Week 12
    -1.42 ( 0.265 )
    -1.36 ( 0.279 )
    -1.44 ( 0.273 )
    -1.23 ( 0.270 )
        Week 16
    -1.77 ( 0.263 )
    -1.27 ( 0.275 )
    -1.55 ( 0.271 )
    -1.55 ( 0.270 )
    No statistical analyses for this end point

    Secondary: Change from baseline in FACIT-F score at Week 24

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    End point title
    		 Change from baseline in FACIT-F score at Week 24
    End point description
    Change in FACIT-F from baseline over 24 weeks as compared to placebo. The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F v4) is a short, 13-item, easy-to-administer tool that measures an individual’s level of fatigue during their usual daily activities over the previous week. The level of fatigue is measured on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The global score ranges between 0 and 52, with higher scores indicating less fatigue.
    End point type
    Secondary
    End point timeframe
    Baseline to 24 weeks
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: Scores on a scale
        least squares mean (standard error)
    9.05 ( 1.404 )
    7.12 ( 1.502 )
    6.48 ( 1.518 )
    9.36 ( 1.436 )
    Statistical analysis title
    		 VAY736 5 mg
    Comparison groups
    Placebo v VAY736 5 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3424
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.93
         upper limit
    		 2.07
    Statistical analysis title
    		 VAY736 300 mg
    Comparison groups
    Placebo v VAY736 300 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.874
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.58
         upper limit
    		 4.2
    Statistical analysis title
    		 VAY736 50 mg
    Comparison groups
    Placebo v VAY736 50 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2092
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.58
         upper limit
    		 1.45

    Secondary: Change from baseline in FACIT-F score at Weeks 4, 8, 12 and 16

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    End point title
    		 Change from baseline in FACIT-F score at Weeks 4, 8, 12 and 16
    End point description
    Change in FACIT-F from baseline as compared to placebo. The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F v4) is a short, 13-item, easy-to-administer tool that measures an individual’s level of fatigue during their usual daily activities over the previous week. The level of fatigue is measured on a four-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The global score ranges between 0 and 52, with higher scores indicating less fatigue.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12 and 16
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    48
    42
    39
    46
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Week 4
    3.78 ( 1.175 )
    6.32 ( 1.239 )
    3.12 ( 1.229 )
    3.39 ( 1.203 )
        Week 8
    5.49 ( 1.222 )
    6.36 ( 1.297 )
    3.93 ( 1.303 )
    5.98 ( 1.250 )
        Week 12
    6.25 ( 1.349 )
    8.17 ( 1.429 )
    5.73 ( 1.427 )
    6.05 ( 1.374 )
        Week 16
    8.56 ( 1.284 )
    7.09 ( 1.357 )
    6.86 ( 1.359 )
    8.30 ( 1.318 )
    No statistical analyses for this end point

    Secondary: Change from baseline in salivary flow rate at Week 24

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    End point title
    		 Change from baseline in salivary flow rate at Week 24
    End point description
    Change from baseline in salivary flow rate (unstimulated and stimulated) at 24 weeks as compared to placebo. Unstimulated saliva is a mix of serous and mucous secretions coming primarily from the submandibular and minor salivary glands. The parotid gland produces the largest volume of stimulated saliva. Stimulated saliva accounts for 80-90% of daily salivary production.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 weeks
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: mL/min
    least squares mean (standard error)
        Stimulated
    0.05 ( 0.067 )
    0.16 ( 0.074 )
    0.18 ( 0.071 )
    0.25 ( 0.98 )
        Unstimulated
    0.12 ( 0.20 )
    0.12 ( 0.17 )
    0.10 ( 0.13 )
    0.25 ( 0.069 )
    Statistical analysis title
    		 VAY736 5 mg
    Statistical analysis description
    Stimulated
    Comparison groups
    Placebo v VAY736 5 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.271
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.08
         upper limit
    		 0.3
    Statistical analysis title
    		 VAY736 50 mg
    Statistical analysis description
    Stimulated
    Comparison groups
    Placebo v VAY736 50 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1618
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 0.32
    Statistical analysis title
    		 VAY736 300 mg
    Statistical analysis description
    Stimulated
    Comparison groups
    Placebo v VAY736 300 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0374
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.01
         upper limit
    		 0.38
    Statistical analysis title
    		 VAY736 5 mg
    Statistical analysis description
    Unstimulated
    Comparison groups
    Placebo v VAY736 5 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9559
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.09
         upper limit
    		 0.09
    Statistical analysis title
    		 VAY736 50 mg
    Statistical analysis description
    Unstimulated
    Comparison groups
    Placebo v VAY736 50 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.929
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.09
         upper limit
    		 0.08
    Statistical analysis title
    		 VAY736 300 mg
    Statistical analysis description
    Unstimulated
    Comparison groups
    Placebo v VAY736 300 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7276
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 0.07

    Secondary: Change from SF-36 physical component (PCS) and mental component (MCS) at Week 24

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    End point title
    		 Change from SF-36 physical component (PCS) and mental component (MCS) at Week 24
    End point description
    Change from SF-36 physical component (PCS) and mental component (MCS) from baseline over 24 weeks as compared to placebo The SF36 includes 8 scale scores (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) and two summary scores, the physical and mental component scores. The first four and last four scales comprise physical and mental component scores, respectively. The range of scores of the physical component (PCS) and mental component (MCS) is 0 (lowest or worst possible level of functioning) to 100 (highest or best possible level of functioning).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: Scores on a scale
    least squares mean (standard error)
        Mental Component Score
    4.63 ( 1.259 )
    3.61 ( 1.350 )
    5.31 ( 1.367 )
    5.63 ( 1.286 )
        Physical Component Score
    3.66 ( 0.952 )
    4.79 ( 1.019 )
    2.66 ( 1.026 )
    5.50 ( 0.972 )
    Statistical analysis title
    		 VAY736 5 mg
    Statistical analysis description
    Mental Component Score
    Comparison groups
    Placebo v VAY736 5 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5768
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.61
         upper limit
    		 2.57
    Statistical analysis title
    		 VAY736 50 mg
    Statistical analysis description
    Mental Component Score
    Comparison groups
    Placebo v VAY736 50 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7113
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.93
         upper limit
    		 4.28
    Statistical analysis title
    		 VAY736 300 mg
    Statistical analysis description
    Mental Component Score
    Comparison groups
    Placebo v VAY736 300 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5722
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.49
         upper limit
    		 4.48
    Statistical analysis title
    		 VAY736 5 mg
    Statistical analysis description
    Physical Component Score
    Comparison groups
    Placebo v VAY736 5 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4138
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.59
         upper limit
    		 3.83
    Statistical analysis title
    		 VAY736 50 mg
    Statistical analysis description
    Physical Component Score
    Comparison groups
    Placebo v VAY736 50 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4663
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.72
         upper limit
    		 1.71
    Statistical analysis title
    		 VAY736 300 mg
    Statistical analysis description
    Physical Component Score
    Comparison groups
    Placebo v VAY736 300 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1694
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    1.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.79
         upper limit
    		 4.47

    Secondary: Change from SF-36 physical component (PCS) and mental component (MCS) from Baseline to Weeks 4, 8, 12 and 16

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    End point title
    		 Change from SF-36 physical component (PCS) and mental component (MCS) from Baseline to Weeks 4, 8, 12 and 16
    End point description
    Change from SF-36 physical component (PCS) and mental component (MCS) from baseline over to 16 weeks as compared to placebo The SF36 includes 8 scale scores (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) and two summary scores, the physical and mental component scores. The first four and last four scales comprise physical and mental component scores, respectively. The range of scores of the physical component (PCS) and mental component (MCS) is 0 (lowest or worst possible level of functioning) to 100 (highest or best possible level of functioning).
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12 and 16
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: Scores on a scale
    least squares mean (standard error)
        Week 4 - Mental Component Score
    0.49 ( 1.091 )
    1.89 ( 1.151 )
    2.46 ( 1.149 )
    2.18 ( 1.116 )
        Week 8 - Mental Component Score
    2.65 ( 2.267 )
    3.80 ( 1.341 )
    4.65 ( 1.363 )
    3.35 ( 1.294 )
        Week 12 - Mental Component Score
    2.89 ( 1.188 )
    5.42 ( 1.264 )
    3.94 ( 1.265 )
    4.59 ( 1.207 )
        Week 16 - Mental Component Score
    4.60 ( 1.214 )
    3.00 ( 1.281 )
    5.57 ( 1.291 )
    5.46 ( 1.247 )
        Week 4 - Physical Component Score
    3.35 ( 0.844 )
    3.94 ( 0.889 )
    1.14 ( 0.878 )
    1.98 ( 0.863 )
        Week 8 - Physical Component Score
    3.83 ( 0.894 )
    4.56 ( 0.949 )
    3.48 ( 0.941 )
    3.47 ( 0.909 )
        Week 12 - Physical Component Score
    3.83 ( 0.894 )
    4.56 ( 0.949 )
    3.48 ( 0.941 )
    3.47 ( 0.909 )
        Week 16 - Physical Component Score
    4.72 ( 0.968 )
    4.67 ( 1.020 )
    3.32 ( 1.021 )
    4.57 ( 0.993 )
    No statistical analyses for this end point

    Secondary: Change from baseline in PhGA of patient’s overall disease activity using Patient Visual Analog Scale (VAS) at 24 weeks

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    End point title
    		 Change from baseline in PhGA of patient’s overall disease activity using Patient Visual Analog Scale (VAS) at 24 weeks
    End point description
    Change from baseline in PhGA of patient’s overall disease activity (recorded by VAS) over 24 weeks as compared to placebo Physician global assessment of overall disease activity (PhGA) was performed using a 100 mm visual analogue scale (VAS) ranging from no disease activity (score 0) to maximal disease activity (score 100), after the question “Considering all the ways the disease affects your patient, draw a line on the scale for how well his or her condition is today”. A negative change from baseline is a favourable outcome.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 weeks
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: Scores on a scale
        least squares mean (standard error)
    -23.64 ( 2.601 )
    -27.81 ( 2.751 )
    -28.13 ( 2.700 )
    -31.99 ( 2.630 )
    Statistical analysis title
    		 VAY736 5 mg
    Comparison groups
    Placebo v VAY736 5 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2671
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -4.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.56
         upper limit
    		 3.22
    Statistical analysis title
    		 VAY736 50 mg
    Comparison groups
    Placebo v VAY736 50 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2248
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -4.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.78
         upper limit
    		 2.79
    Statistical analysis title
    		 VAY736 300 mg
    Comparison groups
    Placebo v VAY736 300 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0224
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -8.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.51
         upper limit
    		 -1.2

    Secondary: Change from baseline in PhGA of patient’s overall disease activity using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16

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    End point title
    		 Change from baseline in PhGA of patient’s overall disease activity using Patient Visual Analog Scale (VAS) at Weeks 4, 8, 12 and 16
    End point description
    Change from baseline in PhGA of patient’s overall disease activity (recorded by VAS) as compared to placebo Change from baseline in PhGA of patient’s overall disease activity (recorded by VAS) over 16 weeks as compared to placebo Physician global assessment of overall disease activity (PhGA) was performed using a 100 mm visual analogue scale (VAS) ranging from no disease activity (score 0) to maximal disease activity (score 100), after the question “Considering all the ways the disease affects your patient, draw a line on the scale for how well his or her condition is today”. A negative change from baseline is a favourable outcome.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12 and 16
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: Scores on a scale
    least squares mean (standard error)
        Week 4
    -12.49 ( 2.327 )
    -10.50 ( 2.445 )
    -12.38 ( 2.361 )
    -18.67 ( 2.367 )
        Week 8
    -18.54 ( 2.239 )
    -16.53 ( 2.338 )
    -22.12 ( 2.374 )
    -24.85 ( 2.289 )
        Week 12
    -21.01 ( 2.299 )
    -20.72 ( 2.413 )
    -25.35 ( 2.341 )
    -27.25 ( 2.305 )
        Week 16
    -19.44 ( 2.572 )
    -24.49 ( 2.687 )
    -24.77 ( 2.676 )
    -25.77 ( 2.633 )
    No statistical analyses for this end point

    Secondary: PaGA Score at Weeks 4, 8, 12, 16 and 24

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    End point title
    		 PaGA Score at Weeks 4, 8, 12, 16 and 24
    End point description
    Patient global assessment (PaGA) Score at Weeks 4, 8, 12, 16 and 24 The PaGA of disease activity was performed using a 100 mm Visual Analog Scale (VAS) ranging from 0 (no disease activity) to 100 (maximal disease activity), in response to the question “Considering all the ways Sjögren’s syndrome affects you, please draw a line on the scale to indicate how well you are doing today”.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12, 16 and 24
    End point values
    		 Placebo VAY736 5 mg VAY736 50 mg VAY736 300 mg
    Number of subjects analysed
    49
    47
    47
    47
    Units: Scores on a scale
    least squares mean (standard error)
        Week 4
    -9.42 ( 2.850 )
    -10.02 ( 2.992 )
    -5.96 ( 2.969 )
    -8.96 ( 2.906 )
        Week 8
    -9.74 ( 3.035 )
    -11.48 ( 3.214 )
    -8.70 ( 3.271 )
    -15.27 ( 3.091 )
        Week 12
    -11.45 ( 3.064 )
    -17.51 ( 3.244 )
    -11.73 ( 3.234 )
    -13.57 ( 3.105 )
        Week 16
    -16.26 ( 3.194 )
    -17.56 ( 3.361 )
    -14.86 ( 3.375 )
    -15.78 ( 3.271 )
        Week 24
    -15.11 ( 3.405 )
    -12.83 ( 3.648 )
    -11.85 ( 3.704 )
    -19.87 ( 3.470 )
    Statistical analysis title
    		 VAY736 5 mg
    Statistical analysis description
    Baseline, Week 24
    Comparison groups
    Placebo v VAY736 5 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6457
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    2.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.46
         upper limit
    		 12
    Statistical analysis title
    		 VAY736 300 mg
    Comparison groups
    Placebo v VAY736 300 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 95
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -4.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.21
         upper limit
    		 4.68
    Statistical analysis title
    		 VAY736 50 mg
    Statistical analysis description
    Baseline, Week 24
    Comparison groups
    Placebo v VAY736 50 mg
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5132
    Method
    		 LS Mean Difference
    Parameter type
    		 LS Mean Difference
    Point estimate
    3.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.55
         upper limit
    		 13.06

    Secondary: Time to Recovery to baseline like values for B-cell counts

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    End point title
    		 Time to Recovery to baseline like values for B-cell counts [1]
    End point description
    Kaplan-Meier Analysis for Time to Recovery to Baseline like Values (defined as at least 80% of baseline counts or ≥ 50 cells/µL) for B-cell counts – Entire Study (FAS) VAY736 300 mg - Placebo includes patients who discontinued in Period 2 and entered Period 4 directly and patients who completed Period 2 and were re-randomized to placebo.
    End point type
    Secondary
    End point timeframe
    Week 24; and then to last dose of administration up to a maximum of 2 years
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No stats analysis were planned.
    End point values
    		 VAY736 5 mg VAY736 50 mg Placebo - VAY150 mg VAY736 300 mg - Placebo
    Number of subjects analysed
    47
    47
    49
    26
    Units: months
        median (confidence interval 95%)
    3.8 (2.7 to 5.2)
    4.8 (4.7 to 6.6)
    6.8 (5.0 to 9.2)
    8.4 (6.8 to 9.1)
    No statistical analyses for this end point

    Secondary: Change from baseline in whole blood CD19+ B-cell counts. Units: percent change from baseline at Week 24

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    End point title
    		 Change from baseline in whole blood CD19+ B-cell counts. Units: percent change from baseline at Week 24 [2]
    End point description
    Change from baseline in whole blood CD19+ B-cell counts. Units: percent change from baseline VAY736 300 mg - Placebo includes patients who discontinued in Period 2 and entered Period 4 directly and patients who completed Period 2 and were re-randomized to placebo. Baseline is defined as the last assessment performed on or prior to the date of administration of the first dose of study treatment. Only patients with baseline measurement and at least one measurement post-baseline were included.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No stats analysis were planned.
    End point values
    		 VAY736 5 mg VAY736 50 mg Placebo - VAY150 mg VAY736 300 mg - Placebo
    Number of subjects analysed
    47
    47
    49
    26
    Units: pg/mL
        least squares mean (standard error)
    150.36 ( 16.229 )
    241.14 ( 16.040 )
    -1.17 ( 15.053 )
    265.77 ( 20.407 )
    No statistical analyses for this end point

    Secondary: Peak serum concentration of VAY736

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    End point title
    		 Peak serum concentration of VAY736 [3]
    End point description
    Pharmacokinetic Concentrations This outcome only applies to patients who received at least one dose of VAY739 (so not applicable to placebo)
    End point type
    Secondary
    End point timeframe
    baseline to week 24
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No stats analysis were planned.
    End point values
    		 VAY736 5 mg VAY736 50 mg VAY736 300 mg VAY736 300 mg - Placebo
    Number of subjects analysed
    47
    47
    4
    21
    Units: ug/mL
        arithmetic mean (standard deviation)
    0.0747 ( 0.203 )
    0.475 ( 0.380 )
    1.46 ( 0.596 )
    2.15 ( 1.47 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information [1]
    Timeframe for reporting adverse events
    AEs were collected from first dose of study treatment until end of study treatment at week 24 and then up to 28 weeks
    Adverse event reporting additional description
    Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Frequency threshold for reporting non-serious adverse events: 5%
    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: Not relevant to this analysis.

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Jan 2017
    The main purpose of this global amendment was to remove inconsistencies and provide clarifications. At the time of this Amendment no patients had been screened or enrolled in the study.
    07 Jan 2020
    As of 16-Dec-2019, the study was fully enrolled and the primary efficacy analysis (when all randomized patients reached Week 24) had been performed. The purpose of this global amendment was to incorporate an additional analysis (Week 52) for reporting study results (interim Clinical Study Report) prior to the final study analysis.
    22 May 2020
    The main purpose of this global amendment was to: a) Remove the Inclusion Criterion of a mandatory salivary/lacrimal gland biopsy result confirming primary Sjögren’s syndrome diagnosis prior to baseline visit; b) Revise the Exclusion Criterion to allow background therapy with azathioprine while on study treatment, for patients who had been treated with a stable dose for at least 3 months prior to randomization; c) Remove the Exclusion Criterion related to the requirement of using male contraception by male study participants; d) Provide more detailed guidance on recommended time window for use of artificial tears, artificial saliva and other salivary stimulants (e.g., cevimeline, pilocarpine) prior to performing the study assessments; e) Revise the timepoint of Inclusion Criterion requirement for ESSDAI score of 6 to be met at Screening period instead of Baseline; f) Add optional collection of the archival biopsy slides from the time of diagnosis for digital copy (scanning) and exploratory analysis; g) Revise the statistical section to remove analyses of exploratory nature and to clarify points for consistency. The study was initiated in Jun-2017 and as of 23-Mar-2018, 47 patients had been randomized.

    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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