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    Clinical Trial Results:
    A 48-week, 6-arm, randomized, double-blind, placebo-controlled multicenter trial to assess the safety and efficacy of multiple CFZ533 doses administered subcutaneously in two distinct populations of patients with Sjogren’s Syndrome (TWINSS)

    Summary
    EudraCT number
    		 2018-004476-35
    Trial protocol
    		 PT   HU   GB   NL   GR   FR   DE   SE   AT   SI   IT   RO  
    Global end of trial date
    06 Jun 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    20 Jun 2024
    First version publication date
    20 Jun 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CCFZ533B2201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03905525
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Jun 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Jun 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives were to demonstrate for Cohort 1 a dose-response of CFZ533 (iscalimab) based on change in ESSDAI from baseline at Week 24, and to estimate for Cohort 2 the effect of CFZ533 (iscalimab) 600 mg subcutaneous (s.c.) on the change in ESSPRI at Week 24.
    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
    01 Oct 2019
    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: 8
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Austria: 11
    Country: Number of subjects enrolled
    Brazil: 14
    Country: Number of subjects enrolled
    Canada: 9
    Country: Number of subjects enrolled
    Chile: 26
    Country: Number of subjects enrolled
    Colombia: 9
    Country: Number of subjects enrolled
    France: 13
    Country: Number of subjects enrolled
    Germany: 25
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    Greece: 3
    Country: Number of subjects enrolled
    Hungary: 15
    Country: Number of subjects enrolled
    Israel: 10
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Japan: 16
    Country: Number of subjects enrolled
    Korea, Republic of: 7
    Country: Number of subjects enrolled
    Netherlands: 8
    Country: Number of subjects enrolled
    Portugal: 12
    Country: Number of subjects enrolled
    Romania: 7
    Country: Number of subjects enrolled
    Russian Federation: 34
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    Türkiye: 5
    Country: Number of subjects enrolled
    United States: 22
    Worldwide total number of subjects
    273
    EEA total number of subjects
    100
    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)
    236
    From 65 to 84 years
    37
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study was conducted at 71 sites in 23 countries worldwide.

    Period 1
    Period 1 title
    Period 1 (up to Week 24): Cohorts 1&2
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1 / Arm D (Period 1): Placebo
    Arm description
    		 Placebo treatment is administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo treatment is administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.

    Arm title
    		 Cohort 1/Arm C: CFZ533 150 mg
    Arm description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 150 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 150 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533 150 mg
    Investigational medicinal product code
    Other name
    Iscalimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 150 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 150 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Arm title
    		 Cohort 1/Arm B: CFZ533 300 mg
    Arm description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 300 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 300 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533 300 mg
    Investigational medicinal product code
    Other name
    Iscalimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 300 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 300 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Arm title
    		 Cohort 1/Arm A: CFZ533 600 mg
    Arm description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Weeks 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533 600 mg
    Investigational medicinal product code
    Other name
    Iscalimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Weeks 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Arm title
    		 Cohort 2/Arm F: Placebo
    Arm description
    		 Placebo treatment was administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo treatment is administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.

    Arm title
    		 Cohort 2/Arm E: CFZ533 600 mg
    Arm description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533 600 mg
    Investigational medicinal product code
    Other name
    Iscalimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25

    Number of subjects in period 1
    		Cohort 1 / Arm D (Period 1): Placebo Cohort 1/Arm C: CFZ533 150 mg Cohort 1/Arm B: CFZ533 300 mg Cohort 1/Arm A: CFZ533 600 mg Cohort 2/Arm F: Placebo Cohort 2/Arm E: CFZ533 600 mg
    Started
    43
    44
    43
    43
    50
    50
    Full analysis set (FAS)
    43
    44
    43
    43
    50
    50
    Continued to Treatment Period 2
    41
    42
    41
    39
    45
    48
    Completed
    41
    42
    41
    39
    44
    48
    Not completed
    2
    2
    2
    4
    6
    2
         Physician decision
    -
    1
    -
    -
    -
    -
         Adverse event, non-fatal
    1
    1
    2
    4
    3
    1
         Subject decision
    -
    -
    -
    -
    3
    1
         Lost to follow-up
    1
    -
    -
    -
    -
    -
    Period 2
    Period 2 title
    Period 2 (up to Week 48): Cohorts 1&2
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Cohort 1/Arm C: CFZ533 150 mg
    Arm description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 150 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 150 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533 150 mg
    Investigational medicinal product code
    Other name
    Iscalimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 150 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 150 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Arm title
    		 Cohort 1/Arm B: CFZ533 300 mg
    Arm description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 300 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 300 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533 300 mg
    Investigational medicinal product code
    Other name
    Iscalimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 300 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 300 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Arm title
    		 Cohort 1/Arm A: CFZ533 600 mg
    Arm description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Weeks 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533 600 mg
    Investigational medicinal product code
    Other name
    Iscalimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Weeks 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Arm title
    		 Cohort 1 / Arm D1 (Period 2): CFZ533 600mg (from Week 24)
    Arm description
    		 3 weekly subcutaneous (s.c.) loading doses of 600 mg iscalimab on Week 24, 25 and 26. After Week 26 and up to Week 46 (last dose), iscalimab was administered bi-weekly at 600 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ 533 mg
    Investigational medicinal product code
    Other name
    Iscalimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Period 2: 3 weekly subcutaneous (s.c.) loading doses of 600 mg iscalimab on Week 24, 25 and 26. After Week 26 and up to Week 46 (last dose), iscalimab was administered bi-weekly at 600 mg.

    Arm title
    		 Cohort 2/Arm E: CFZ533 600 mg
    Arm description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533 600 mg
    Investigational medicinal product code
    Other name
    Iscalimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25

    Arm title
    		 Cohort 2 / Arm F1 (Period 2): CFZ533 300mg
    Arm description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab: 600 mg on Week 24, and 300 mg on Week 25 and Week 26. After Week 26, iscalimab was administered s.c. bi-weekly at 300 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CFZ533 300 mg
    Investigational medicinal product code
    Other name
    Iscalimab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Period 2: 3 weekly subcutaneous (s.c.) loading doses of iscalimab: 600 mg on Week 24, and 300 mg on Week 25 and Week 26. After Week 26, iscalimab was administered s.c. bi-weekly at 300 mg.

    Number of subjects in period 2
    		Cohort 1/Arm C: CFZ533 150 mg Cohort 1/Arm B: CFZ533 300 mg Cohort 1/Arm A: CFZ533 600 mg Cohort 1 / Arm D1 (Period 2): CFZ533 600mg (from Week 24) Cohort 2/Arm E: CFZ533 600 mg Cohort 2 / Arm F1 (Period 2): CFZ533 300mg
    Started
    42
    41
    39
    41
    48
    45
    Continued to Post-Tx FUP Period
    42
    40
    39
    41
    46
    45
    Completed
    38
    36
    39
    39
    41
    44
    Not completed
    4
    5
    0
    2
    7
    1
         Adverse event, serious fatal
    -
    1
    -
    -
    1
    -
         Withdrawal of Consent
    -
    1
    -
    -
    -
    -
         Physician decision
    -
    1
    -
    -
    -
    -
         Adverse event, non-fatal
    1
    1
    -
    -
    1
    1
         Subject decision
    3
    1
    -
    2
    4
    -
         Protocol deviation
    -
    -
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1 / Arm D (Period 1): Placebo
    Reporting group description
    		 Placebo treatment is administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.

    Reporting group title
    Cohort 1/Arm C: CFZ533 150 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 150 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 150 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group title
    Cohort 1/Arm B: CFZ533 300 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 300 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 300 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group title
    Cohort 1/Arm A: CFZ533 600 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Weeks 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group title
    Cohort 2/Arm F: Placebo
    Reporting group description
    		 Placebo treatment was administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.

    Reporting group title
    Cohort 2/Arm E: CFZ533 600 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group values
    		 Cohort 1 / Arm D (Period 1): Placebo Cohort 1/Arm C: CFZ533 150 mg Cohort 1/Arm B: CFZ533 300 mg Cohort 1/Arm A: CFZ533 600 mg Cohort 2/Arm F: Placebo Cohort 2/Arm E: CFZ533 600 mg Total
    Number of subjects
    		 43 44 43 43 50 50 273
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 38 38 39 37 44 40 236
        From 65-84 years
    		 5 6 4 6 6 10 37
        85 years and over
    		 0 0 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 53.3 ( 9.55 ) 49.3 ( 14.41 ) 48.7 ( 12.78 ) 52.6 ( 12.31 ) 49.4 ( 13.40 ) 53.6 ( 13.18 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 41 42 41 40 48 50 262
        Male
    		 2 2 2 3 2 0 11
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 1 1 0 1 4
        Asian
    		 3 4 4 5 7 8 31
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0
        Black or African American
    		 1 1 2 1 3 3 11
        White
    		 38 37 35 35 38 37 220
        More than one race
    		 1 1 1 1 1 0 5
        Unknown or Not Reported
    		 0 0 0 0 1 1 2

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1 / Arm D (Period 1): Placebo
    Reporting group description
    		 Placebo treatment is administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.

    Reporting group title
    Cohort 1/Arm C: CFZ533 150 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 150 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 150 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group title
    Cohort 1/Arm B: CFZ533 300 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 300 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 300 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group title
    Cohort 1/Arm A: CFZ533 600 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Weeks 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group title
    Cohort 2/Arm F: Placebo
    Reporting group description
    		 Placebo treatment was administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.

    Reporting group title
    Cohort 2/Arm E: CFZ533 600 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
    Reporting group title
    Cohort 1/Arm C: CFZ533 150 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 150 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 150 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group title
    Cohort 1/Arm B: CFZ533 300 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 300 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 300 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group title
    Cohort 1/Arm A: CFZ533 600 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Weeks 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group title
    Cohort 1 / Arm D1 (Period 2): CFZ533 600mg (from Week 24)
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of 600 mg iscalimab on Week 24, 25 and 26. After Week 26 and up to Week 46 (last dose), iscalimab was administered bi-weekly at 600 mg.

    Reporting group title
    Cohort 2/Arm E: CFZ533 600 mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.

    Reporting group title
    Cohort 2 / Arm F1 (Period 2): CFZ533 300mg
    Reporting group description
    		 3 weekly subcutaneous (s.c.) loading doses of iscalimab: 600 mg on Week 24, and 300 mg on Week 25 and Week 26. After Week 26, iscalimab was administered s.c. bi-weekly at 300 mg.

    Subject analysis set title
    Cohort 1: Placebo
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: Placebo

    Subject analysis set title
    Cohort 1: CFZ533 150 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 150 mg

    Subject analysis set title
    Cohort 1: CFZ533 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 600 mg

    Subject analysis set title
    Cohort 1: CFZ533 600 mg 24 Weeks
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 600 mg 24 Weeks

    Subject analysis set title
    Cohort 1: CFZ533 150 mg 48 Weeks
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 150 mg 48 Weeks

    Subject analysis set title
    Cohort 1: CFZ533 300 mg 48 Weeks
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 300 mg 48 Weeks

    Subject analysis set title
    Cohort 1: CFZ533 600 mg 48 Weeks
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 600 mg 48 Weeks

    Subject analysis set title
    Any CFZ533 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants from cohort 1 who received CFZ533 600 mg in all Study Periods (including placebo patients who switched to CFZ533 600 mg at Week 24)

    Subject analysis set title
    Any CFZ533
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants from cohort 1 who received a dose of CFZ533 during the study

    Subject analysis set title
    Cohort 2: Placebo
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 2: Placebo

    Subject analysis set title
    Cohort 2: CFZ533 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 2: CFZ533 600 mg

    Subject analysis set title
    Cohort 2: CFZ533 300 mg 24 Weeks
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 2: CFZ533 300 mg 24 Weeks

    Subject analysis set title
    Cohort 2: CFZ533 600 mg 48 Weeks
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 2: CFZ533 600 mg 48 Weeks

    Subject analysis set title
    Any CFZ533
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants from cohort 2 who received a dose of CFZ533 during the study

    Subject analysis set title
    Cohort 1: Placebo - CFZ533 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: Placebo - CFZ533 600 mg

    Subject analysis set title
    Cohort 1: CFZ533 150 mg - CFZ533 150 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 150 mg - CFZ533 150 mg

    Subject analysis set title
    Cohort 1: CFZ533 300 mg - CFZ533 300 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 300 mg - CFZ533 300 mg

    Subject analysis set title
    Cohort 1: CFZ533 600 mg - CFZ533 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 600 mg - CFZ533 600 mg

    Subject analysis set title
    Cohort 2: Placebo - CFZ533 300 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 2: Placebo - CFZ533 300 mg

    Subject analysis set title
    Cohort 2: CFZ533 600 mg - CFZ533 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 2: CFZ533 600 mg - CFZ533 600 mg

    Subject analysis set title
    Cohort 1: Placebo - CFZ533 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: Placebo - CFZ533 600 mg

    Subject analysis set title
    Cohort 1: CFZ533 150 mg - CFZ533 150 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 150 mg - CFZ533 150 mg

    Subject analysis set title
    Cohort 1: CFZ533 300 mg - CFZ533 300 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 300 mg - CFZ533 300 mg

    Subject analysis set title
    Cohort 1: CFZ533 600 mg - CFZ533 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 600 mg - CFZ533 600 mg

    Subject analysis set title
    Cohort 2: Placebo - CFZ533 300 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 2: Placebo - CFZ533 300 mg

    Subject analysis set title
    Cohort 1: CFZ533 150 mg - CFZ533 150 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 150 mg - CFZ533 150 mg

    Subject analysis set title
    Cohort 1: CFZ533 600 mg - CFZ533 600 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 1: CFZ533 600 mg - CFZ533 600 mg

    Subject analysis set title
    Cohort 2: Placebo - CFZ533 300 mg
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Cohort 2: Placebo - CFZ533 300 mg

    Primary: Cohort 1: Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score from baseline at 24 weeks as compared to placebo

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    End point title
    		 Cohort 1: Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score from baseline at 24 weeks as compared to placebo [1]
    End point description
    ESSDAI is a validated disease outcome measure for SjS that contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The domains (weights) are as follows: constitutional (3), lymphadenopathy (4), glandular (2), articular (2), cutaneous (3), pulmonary (5), renal (5), muscular (6), peripheral nervous system (PNS) (5), central nervous system (CNS) (5), hematological (2) and biological (1). The total score may vary between 0-123. It is considered low activity an ESSDAI < 5; moderate activity 5-13, and high activity if ESSDAI is >= 14.
    End point type
    Primary
    End point timeframe
    Baseline, Week 24
    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: This endpoint is only applicable to participants in Cohort 1
    End point values
    		 Cohort 1 / Arm D (Period 1): Placebo Cohort 1/Arm C: CFZ533 150 mg Cohort 1/Arm B: CFZ533 300 mg Cohort 1/Arm A: CFZ533 600 mg
    Number of subjects analysed
    41
    42
    41
    39
    Units: Unit on a scale
        least squares mean (standard error)
    -4.0 ( 0.73 )
    -7.0 ( 0.70 )
    -5.4 ( 0.71 )
    -6.9 ( 0.73 )
    Statistical analysis title
    		 ESSDAI score at 24 weeks - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm C: CFZ533 150 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0025
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.9
         upper limit
    		 -1.1
    Statistical analysis title
    		 ESSDAI score at 24 weeks - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm B: CFZ533 300 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1578
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 0.5
    Statistical analysis title
    		 ESSDAI score at 24 weeks - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm A: CFZ533 600 mg
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0037
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.9
         upper limit
    		 -1

    Primary: Cohort 2: Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score from baseline at 24 weeks as compared to placebo.

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    End point title
    		 Cohort 2: Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score from baseline at 24 weeks as compared to placebo. [2]
    End point description
    The ESSPRI is a self-evaluation index for measuring symptoms including pain, fatigue and dryness. Each symptom was measured with a single 0 (no symptoms) to 10 (severe symptoms) numerical scale and the final ESSPRI score is calculated by averaging these domains with a maximum severity score of 10.
    End point type
    Primary
    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: This endpoint is only applicable to participants in Cohort 2
    End point values
    		 Cohort 2/Arm F: Placebo Cohort 2/Arm E: CFZ533 600 mg
    Number of subjects analysed
    45
    49
    Units: Unit on a scale
        least squares mean (standard error)
    -1.21 ( 0.271 )
    -1.79 ( 0.258 )
    Statistical analysis title
    		 ESSPRI score at 24 weeks - Cohort 2
    Comparison groups
    Cohort 2/Arm F: Placebo v Cohort 2/Arm E: CFZ533 600 mg
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.121
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 0.15

    Secondary: Cohort 1: Change from baseline in ESSPRI at Week 24

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    End point title
    		 Cohort 1: Change from baseline in ESSPRI at Week 24 [3]
    End point description
    The ESSPRI is a self-evaluation index for measuring symptoms including pain, fatigue and dryness. Each symptom was measured with a single 0 (no symptoms) to 10 (severe symptoms) numerical scale and the final ESSPRI score is calculated by averaging these domains with a maximum severity score of 10.
    End point type
    Secondary
    End point timeframe
    Baseline, 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: This endpoint is only applicable to participants in Cohort 1
    End point values
    		 Cohort 1 / Arm D (Period 1): Placebo Cohort 1/Arm C: CFZ533 150 mg Cohort 1/Arm B: CFZ533 300 mg Cohort 1/Arm A: CFZ533 600 mg
    Number of subjects analysed
    39
    42
    40
    39
    Units: Unit on a scale
        least squares mean (standard error)
    -1.3 ( 0.31 )
    -1.8 ( 0.30 )
    -1.6 ( 0.31 )
    -1.8 ( 0.31 )
    Statistical analysis title
    		 ESSPRI at Week 24 - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm C: CFZ533 150 mg
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2078
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.3
    Statistical analysis title
    		 ESSPRI at Week 24 - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm A: CFZ533 600 mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1998
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -0.5
    Confidence interval
         level
    		 0.2%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.3
    Statistical analysis title
    		 ESSPRI at Week 24 - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm B: CFZ533 300 mg
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5132
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.6

    Secondary: Cohort 1: Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24

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    End point title
    		 Cohort 1: Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24 [4]
    End point description
    The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F version 4) is a 13-item, easy-to-administer tool that measures an individual’s level of fatigue during their usual daily activities over the past week. The level of fatigue was measured on a 5-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much) except 2 items which were reversed scored. Final score range is 0-52 with lower scores indicating severe fatigue.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 weeks
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only applicable to participants in Cohort 1
    End point values
    		 Cohort 1 / Arm D (Period 1): Placebo Cohort 1/Arm C: CFZ533 150 mg Cohort 1/Arm B: CFZ533 300 mg Cohort 1/Arm A: CFZ533 600 mg
    Number of subjects analysed
    40
    42
    40
    39
    Units: Unit on a scale
        least squares mean (standard error)
    7.0 ( 1.48 )
    8.6 ( 1.45 )
    8.0 ( 1.47 )
    10.3 ( 1.50 )
    Statistical analysis title
    		 FACIT-F at Week 24 - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm C: CFZ533 150 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4363
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 5.6
    Statistical analysis title
    		 FACIT-F at Week 24 - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm A: CFZ533 600 mg
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.105
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 7.3
    Statistical analysis title
    		 FACIT-F at Week 24 - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm B: CFZ533 300 mg
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6181
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3
         upper limit
    		 5

    Secondary: Cohort 1: Change from baseline in Physician Global Assessment (PhGA) at Week 24

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    End point title
    		 Cohort 1: Change from baseline in Physician Global Assessment (PhGA) at Week 24 [5]
    End point description
    Physician's global assessment (PhGA) of disease activity was performed using a Visual Analog Scale (VAS) - an unnumbered 100 mm horizontal line ranging from "no disease activity" (score 0) to "maximal disease activity" (score 100). The assessment of patient's condition on the day is made by placing a vertical mark across the line.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 weeks
    Notes
    [5] - 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: This endpoint is only applicable to participants in Cohort 1
    End point values
    		 Cohort 1 / Arm D (Period 1): Placebo Cohort 1/Arm C: CFZ533 150 mg Cohort 1/Arm B: CFZ533 300 mg Cohort 1/Arm A: CFZ533 600 mg
    Number of subjects analysed
    36
    40
    35
    39
    Units: Unit on a scale
        least squares mean (standard error)
    -23.9 ( 2.94 )
    -31.6 ( 2.83 )
    -30.8 ( 3.00 )
    -27.0 ( 2.87 )
    Statistical analysis title
    		 PhGA at Week 24 - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm C: CFZ533 150 mg
    Number of subjects included in analysis
    76
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0561
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -7.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.6
         upper limit
    		 0.2
    Statistical analysis title
    		 PhGA at Week 24 - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm B: CFZ533 300 mg
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0974
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -6.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15
         upper limit
    		 1.3
    Statistical analysis title
    		 PhGA at Week 24 - Cohort 1
    Comparison groups
    Cohort 1 / Arm D (Period 1): Placebo v Cohort 1/Arm A: CFZ533 600 mg
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4433
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -3.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11
         upper limit
    		 4.8

    Secondary: Cohort 2: Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24

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    End point title
    		 Cohort 2: Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24 [6]
    End point description
    The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F version 4) is a 13-item, easy-to-administer tool that measures an individual’s level of fatigue during their usual daily activities over the past week. The level of fatigue was measured on a 5-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much) except 2 items which were reversed scored. Final score range is 0-52 with lower scores indicating severe fatigue.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 weeks
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only applicable to participants in Cohort 2
    End point values
    		 Cohort 2/Arm F: Placebo Cohort 2/Arm E: CFZ533 600 mg
    Number of subjects analysed
    45
    49
    Units: Unit on a scale
        least squares mean (standard error)
    5.7 ( 1.32 )
    7.3 ( 1.25 )
    Statistical analysis title
    		 FACIT-F at Week 24 - Cohort 2
    Comparison groups
    Cohort 2/Arm F: Placebo v Cohort 2/Arm E: CFZ533 600 mg
    Number of subjects included in analysis
    94
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3675
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.9
         upper limit
    		 5.1

    Secondary: Cohort 2: Change from baseline in Physician Global Assessment (PhGA) at Week 24

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    End point title
    		 Cohort 2: Change from baseline in Physician Global Assessment (PhGA) at Week 24 [7]
    End point description
    Physician's global assessment (PhGA) of disease activity was performed using a Visual Analog Scale (VAS) - an unnumbered 100 mm horizontal line ranging from "no disease activity" (score 0) to "maximal disease activity" (score 100). The assessment of patient's condition on the day is made by placing a vertical mark across the line.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 weeks
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only applicable to participants in Cohort 2
    End point values
    		 Cohort 2/Arm F: Placebo Cohort 2/Arm E: CFZ533 600 mg
    Number of subjects analysed
    45
    46
    Units: Unit on a scale
        least squares mean (standard error)
    -10.4 ( 2.37 )
    -15.8 ( 2.29 )
    Statistical analysis title
    		 PhGA at Week 24 - Cohort 2
    Comparison groups
    Cohort 2/Arm F: Placebo v Cohort 2/Arm E: CFZ533 600 mg
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1014
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -5.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.8
         upper limit
    		 1.1

    Secondary: Cohort 2: Change from baseline in ESSDAI at Week 24

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    End point title
    		 Cohort 2: Change from baseline in ESSDAI at Week 24 [8]
    End point description
    ESSDAI is a validated disease outcome measure for SjS that contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The domains (weights) are as follows: constitutional (3), lymphadenopathy (4), glandular (2), articular (2), cutaneous (3), pulmonary (5), renal (5), muscular (6), peripheral nervous system (PNS) (5), central nervous system (CNS) (5), hematological (2) and biological (1). The final score may vary between 0-123. It is considered low activity an ESSDAI < 5; moderate activity 5-13, and high activity if ESSDAI is >= 14.
    End point type
    Secondary
    End point timeframe
    Baseline, week 24
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only applicable to participants in Cohort 2
    End point values
    		 Cohort 2/Arm F: Placebo Cohort 2/Arm E: CFZ533 600 mg
    Number of subjects analysed
    45
    47
    Units: Unit on a scale
        least squares mean (standard error)
    0.2 ( 0.33 )
    -0.3 ( 0.32 )
    Statistical analysis title
    		 ESSDAI at Week 24 - Cohort 2
    Comparison groups
    Cohort 2/Arm F: Placebo v Cohort 2/Arm E: CFZ533 600 mg
    Number of subjects included in analysis
    92
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2694
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean difference CFZ533-Placebo
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 0.4

    Secondary: Cohort 2: Proportion of subjects with at least 12 points improvement measured by score of Impact of Dry Eye on Everyday Life (IDEEL) questionnaire symptom bother module at Week 24.

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    End point title
    		 Cohort 2: Proportion of subjects with at least 12 points improvement measured by score of Impact of Dry Eye on Everyday Life (IDEEL) questionnaire symptom bother module at Week 24. [9]
    End point description
    The Impact of Dry Eye on Everyday Life (IDEEL) questionnaire is a comprehensive dry eye specific questionnaire to evaluate treatment satisfaction, symptom-related bother and impact on daily life in a population with dry eye. This study only utilized the Dry Eye Symptom-Bother module. The Dry Eye Symptom-Bother module of IDEEL is composed of a single dimension (20 items). A 4-point Likert-like scale is used: from “not at all” to “very much”. Patients could also answer “I did not have this symptom / Not applicable”. One item is scored on a 5-point Likert-like scale from “none of the time” to “all of the time”. The range for the symptom-bother score is 0 to 100, with higher scores indicating greater symptom bother.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only applicable to participants in Cohort 2
    End point values
    		 Cohort 2/Arm F: Placebo Cohort 2/Arm E: CFZ533 600 mg
    Number of subjects analysed
    50
    50
    Units: Participants
    20
    24
    Statistical analysis title
    		 IDEEL up to Week 24 - Cohort 2
    Comparison groups
    Cohort 2/Arm F: Placebo v Cohort 2/Arm E: CFZ533 600 mg
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5459
    Method
    		 Fisher exact
    Parameter type
    		 Clopper-Pearson method
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.4
         upper limit
    		 27.4

    Secondary: Cohort 1: Incidence of adverse events (AEs), serious adverse events (SAEs) up to Week 24

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    End point title
    		 Cohort 1: Incidence of adverse events (AEs), serious adverse events (SAEs) up to Week 24 [10]
    End point description
    The distribution of adverse events in Treatment Period 1 was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) up to Week 24 (Period 1) is presented by actual treatment during Period 1, with data from separate cohort for the CFZ533 600mg and for the Placebo groups: CFZ533 600 mg, CFZ533 300 mg, CFZ533 150 mg and placebo.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only applicable to participants in Cohort 1
    End point values
    		 Cohort 1/Arm B: CFZ533 300 mg Cohort 1: Placebo Cohort 1: CFZ533 150 mg Cohort 1: CFZ533 600 mg
    Number of subjects analysed
    42
    43
    44
    44
    Units: Participants
        Death
    0
    0
    0
    0
        Adverse Event
    32
    31
    38
    35
        Serious Adverse Event
    3
    1
    1
    4
        AE leading to study medication discontinuation
    1
    1
    1
    5
    No statistical analyses for this end point

    Secondary: Cohort 1: Incidence of adverse events (AEs), serious adverse events (SAEs) in all Study Periods

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    End point title
    		 Cohort 1: Incidence of adverse events (AEs), serious adverse events (SAEs) in all Study Periods
    End point description
    The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) for period 2/3 or overall study is presented by actual treatment sequence during periods 1 and 2, where the CFZ533 600 mg – CFZ533 600 mg sequence included data from patients in separate cohort. CFZ533 600 mg 24 Weeks arm includes only patients from Placebo – CFZ533 600 mg arm, who took at least one CFZ533 600 mg dose in Period 2 (Patients who received Placebo in Period 1 and discontinued before Week 24 are not included). CFZ533 600 mg 48 Weeks arm includes all subjects from CFZ533 600 mg - CFZ533 600 mg arm, and subjects from CFZ533 150 mg - CFZ533 150 mg and CFZ533 300 mg - CFZ533 300 mg arms but only took the first or the first two loading dose(s) in period 1.
    End point type
    Secondary
    End point timeframe
    up to 14 weeks following the last dose of study treatment, up to maximum Week 60
    End point values
    		 Cohort 1: CFZ533 600 mg 24 Weeks Cohort 1: CFZ533 150 mg 48 Weeks Cohort 1: CFZ533 300 mg 48 Weeks Cohort 1: CFZ533 600 mg 48 Weeks Any CFZ533 600 mg Any CFZ533
    Number of subjects analysed
    41
    44
    42
    44
    85
    171
    Units: Participants
        Death
    0
    0
    1
    0
    0
    1
        Adverse Event
    34
    40
    38
    43
    77
    155
        Serious Adverse Event
    4
    6
    6
    6
    10
    22
        AE leading to study medication discontinuation
    0
    2
    3
    5
    5
    10
    No statistical analyses for this end point

    Secondary: Cohort 2: Incidence of adverse events (AEs), serious adverse events (SAEs) up to Week 24

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    End point title
    		 Cohort 2: Incidence of adverse events (AEs), serious adverse events (SAEs) up to Week 24
    End point description
    The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) up to Week 24 (Period 1) is presented by actual treatment during Period 1, with data from separate cohort for the CFZ533 600mg and for the Placebo groups: CFZ533 600 mg and placebo.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    		 Cohort 2: Placebo Cohort 2: CFZ533 600 mg
    Number of subjects analysed
    50
    50
    Units: Participants
        Death
    0
    0
        Adverse Event
    32
    41
        Serious Adverse Event
    2
    2
        AE leading to study medication discontinuation
    3
    1
    No statistical analyses for this end point

    Secondary: Cohort 2: Incidence of adverse events (AEs), serious adverse events (SAEs) in all Study Periods

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    End point title
    		 Cohort 2: Incidence of adverse events (AEs), serious adverse events (SAEs) in all Study Periods
    End point description
    The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) for period 2/3 or overall study is presented by actual treatment sequence during periods 1 and 2, where the CFZ533 600 mg – CFZ533 600 mg sequence included data from patients in separate cohort. CFZ533 300 mg 24 Weeks includes only patients from Placebo - CFZ533 300 mg arm, who received Placebo in Period 1, and either took CFZ533 600 mg loading dose + at least two CFZ533 300 mg subsequent doses in Period 2 or missed CFZ533 600 mg loading dose and took at least one CFZ533 300 mg dose in Period 2 (Patients who received Placebo in Period 1 and discontinued before Week24 are not included). CFZ533 600 mg 48 Weeks arm includes all subjects from CFZ533 600 mg - CFZ533 600 mg arm.
    End point type
    Secondary
    End point timeframe
    up to 14 weeks following the last dose of study treatment, up to maximum Week 60
    End point values
    		 Cohort 2: CFZ533 300 mg 24 Weeks Cohort 2: CFZ533 600 mg 48 Weeks Any CFZ533
    Number of subjects analysed
    44
    50
    94
    Units: Participants
        Death
    0
    1
    1
        Adverse Event
    35
    44
    79
        Serious Adverse Event
    5
    6
    11
        AE leading to study medication discontinuation
    0
    3
    3
    No statistical analyses for this end point

    Secondary: Cohort 1: Change from Baseline in Serum Free Light Kappa (FLCκ) chains levels

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    End point title
    		 Cohort 1: Change from Baseline in Serum Free Light Kappa (FLCκ) chains levels
    End point description
    Serum samples for free light kappa (FLCκ) chains were collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 40, Week 48 (End Treatment Period 2), FUP2 (Week 56), FUP 3 (Week 60)
    End point values
    		 Cohort 1: Placebo - CFZ533 600 mg Cohort 1: CFZ533 150 mg - CFZ533 150 mg Cohort 1: CFZ533 300 mg - CFZ533 300 mg Cohort 1: CFZ533 600 mg - CFZ533 600 mg
    Number of subjects analysed
    42
    41
    41
    38
    Units: mg/L
    least squares mean (standard error)
        Week 4
    -1.9 ( 1.85 )
    -7.2 ( 1.86 )
    -5.4 ( 1.86 )
    -5.5 ( 1.92 )
        Week 12
    -1.1 ( 2.02 )
    -9.7 ( 2.01 )
    -8.8 ( 2.03 )
    -8.6 ( 2.08 )
        Week 24 (End Treatment Period 1)
    0.2 ( 2.26 )
    -9.9 ( 2.26 )
    -10.1 ( 2.28 )
    -11.3 ( 2.35 )
        Week 32
    -8.6 ( 2.17 )
    -11.8 ( 2.17 )
    -11.1 ( 2.18 )
    -8.9 ( 2.26 )
        Week 40
    -11.3 ( 2.05 )
    -12.0 ( 2.06 )
    -13.5 ( 2.07 )
    -11.0 ( 2.13 )
        Week 48 (End Treatment Period 2)
    -13.9 ( 2.25 )
    -12.5 ( 2.25 )
    -13.1 ( 2.27 )
    -11.6 ( 2.32 )
        FUP2 (Week 56)
    -11.8 ( 2.03 )
    -5.6 ( 1.99 )
    -8.9 ( 2.01 )
    -12.4 ( 2.06 )
        FUP 3 (Week 60)
    -9.3 ( 2.07 )
    -3.9 ( 2.04 )
    -4.1 ( 2.07 )
    -10.3 ( 2.11 )
    No statistical analyses for this end point

    Secondary: Cohort 2: Change from Baseline in Serum Free Light Kappa (FLCκ) chains levels

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    End point title
    		 Cohort 2: Change from Baseline in Serum Free Light Kappa (FLCκ) chains levels
    End point description
    Serum samples for free light kappa (FLCκ) chains were collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 40, Week 48 (End Treatment Period 2), FUP2 (Week 56), FUP 3 (Week 60)
    End point values
    		 Cohort 2: Placebo - CFZ533 300 mg Cohort 2: CFZ533 600 mg - CFZ533 600 mg
    Number of subjects analysed
    46
    49
    Units: mg/L
    least squares mean (standard error)
        Week 4
    0.3 ( 0.92 )
    -4.3 ( 0.87 )
        Week 12
    0.1 ( 1.10 )
    -7.2 ( 1.06 )
        Week 24 (End Treatment Period 1)
    -0.2 ( 0.90 )
    -9.9 ( 0.86 )
        Week 32
    -6.0 ( 0.93 )
    -10.5 ( 0.89 )
        Week 40
    -7.8 ( 0.93 )
    -9.9 ( 0.91 )
        Week 48 (End Treatment Period 2)
    -9.3 ( 0.95 )
    -11.9 ( 0.92 )
        FUP2 (Week 56)
    -6.1 ( 1.00 )
    -11.7 ( 0.99 )
        FUP 3 (Week 60)
    -1.9 ( 1.11 )
    -11.0 ( 1.09 )
    No statistical analyses for this end point

    Secondary: Cohort 1: Change from Baseline in Immunoglobulin G (IgG) levels

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    End point title
    		 Cohort 1: Change from Baseline in Immunoglobulin G (IgG) levels
    End point description
    Plasma samples for Immunoglobulin G (IgG) were collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
    End point values
    		 Cohort 1: Placebo - CFZ533 600 mg Cohort 1: CFZ533 150 mg - CFZ533 150 mg Cohort 1: CFZ533 300 mg - CFZ533 300 mg Cohort 1: CFZ533 600 mg - CFZ533 600 mg
    Number of subjects analysed
    43
    43
    43
    41
    Units: g/L
    least squares mean (standard error)
        Week 4
    0.1 ( 0.31 )
    -0.9 ( 0.31 )
    -0.6 ( 0.31 )
    -0.8 ( 0.32 )
        Week 8
    0.0 ( 0.31 )
    -1.1 ( 0.31 )
    -1.0 ( 0.31 )
    -1.4 ( 0.31 )
        Week 12
    0.4 ( 0.28 )
    -1.7 ( 0.27 )
    -1.7 ( 0.28 )
    -1.5 ( 0.28 )
        Week 16
    0.4 ( 0.39 )
    -1.8 ( 0.39 )
    -2.2 ( 0.39 )
    -2.0 ( 0.40 )
        Week 20
    0.1 ( 0.35 )
    -2.4 ( 0.34 )
    -2.3 ( 0.35 )
    -2.1 ( 0.36 )
        Week 24 (End Treatment Period 1)
    0.0 ( 0.36 )
    -2.1 ( 0.35 )
    -2.5 ( 0.36 )
    -2.5 ( 0.36 )
        Week 28
    -0.9 ( 0.39 )
    -2.3 ( 0.38 )
    -2.7 ( 0.39 )
    -2.9 ( 0.39 )
        Week 32
    -1.3 ( 0.36 )
    -2.6 ( 0.36 )
    -3.0 ( 0.36 )
    -3.3 ( 0.37 )
        Week 40
    -2.3 ( 0.36 )
    -2.7 ( 0.36 )
    -3.2 ( 0.36 )
    -3.1 ( 0.36 )
        Week 48 (End Treatment Period 2)
    -3.0 ( 0.40 )
    -2.8 ( 0.40 )
    -3.7 ( 0.41 )
    -3.4 ( 0.40 )
        FUP1 (Week 52)
    -3.6 ( 0.47 )
    -2.9 ( 0.46 )
    -3.8 ( 0.47 )
    -3.7 ( 0.46 )
        FUP2 (Week 56)
    -3.0 ( 0.45 )
    -2.0 ( 0.43 )
    -3.2 ( 0.44 )
    -3.9 ( 0.44 )
        FUP 3 (Week 60)
    -2.9 ( 0.47 )
    -1.2 ( 0.46 )
    -1.9 ( 0.47 )
    -3.3 ( 0.46 )
    No statistical analyses for this end point

    Secondary: Cohort 2: Change from Baseline in Immunoglobulin G (IgG) levels

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    End point title
    		 Cohort 2: Change from Baseline in Immunoglobulin G (IgG) levels
    End point description
    Plasma samples for Immunoglobulin G (IgG) were collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
    End point values
    		 Cohort 2: CFZ533 600 mg - CFZ533 600 mg Cohort 2: Placebo - CFZ533 300 mg
    Number of subjects analysed
    49
    47
    Units: g/L
    least squares mean (standard error)
        Week 4
    -0.8 ( 0.24 )
    -0.8 ( 0.25 )
        Week 8
    -1.9 ( 0.27 )
    -0.5 ( 0.28 )
        Week 12
    -2.5 ( 0.29 )
    -0.4 ( 0.30 )
        Week 16
    -3.0 ( 0.30 )
    -0.6 ( 0.32 )
        Week 20
    -3.2 ( 0.30 )
    -0.7 ( 0.32 )
        Week 24 (End Treatment Period 1)
    -3.6 ( 0.40 )
    0.0 ( 0.42 )
        Week 28
    -4.2 ( 0.36 )
    -1.3 ( 0.38 )
        Week 32
    -4.1 ( 0.34 )
    -1.5 ( 0.35 )
        Week 40
    -4.9 ( 0.42 )
    -2.6 ( 0.43 )
        Week 48 (End Treatment Period 2)
    -4.5 ( 0.43 )
    -3.2 ( 0.43 )
        FUP1 (Week 52)
    -5.0 ( 0.44 )
    -4.0 ( 0.45 )
        FUP2 (Week 56)
    -4.8 ( 0.45 )
    -3.3 ( 0.46 )
        FUP 3 (Week 60)
    -4.5 ( 0.45 )
    -2.4 ( 0.46 )
    No statistical analyses for this end point

    Secondary: Cohort 1: Change from Baseline in Immunoglobulin M (IgM) levels

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    End point title
    		 Cohort 1: Change from Baseline in Immunoglobulin M (IgM) levels
    End point description
    Plasma samples for Immunoglobulin M (IgM) were collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
    End point values
    		 Cohort 1: Placebo - CFZ533 600 mg Cohort 1: CFZ533 150 mg - CFZ533 150 mg Cohort 1: CFZ533 300 mg - CFZ533 300 mg Cohort 1: CFZ533 600 mg - CFZ533 600 mg
    Number of subjects analysed
    43
    43
    43
    41
    Units: g/L
    least squares mean (standard error)
        Week 4
    0.0 ( 0.04 )
    -0.1 ( 0.04 )
    -0.1 ( 0.04 )
    -0.1 ( 0.04 )
        Week 8
    0.0 ( 0.04 )
    -0.2 ( 0.04 )
    -0.3 ( 0.04 )
    -0.2 ( 0.04 )
        Week 12
    0.0 ( 0.04 )
    -0.2 ( 0.04 )
    -0.3 ( 0.04 )
    -0.2 ( 0.04 )
        Week 16
    0.0 ( 0.05 )
    -0.2 ( 0.05 )
    -0.3 ( 0.05 )
    -0.3 ( 0.05 )
        Week 20
    0.0 ( 0.05 )
    -0.2 ( 0.05 )
    -0.4 ( 0.05 )
    -0.3 ( 0.05 )
        Week 24 (End Treatment Period 1)
    0.0 ( 0.06 )
    -0.2 ( 0.06 )
    -0.4 ( 0.06 )
    -0.3 ( 0.06 )
        Week 28
    -0.1 ( 0.05 )
    -0.2 ( 0.05 )
    -0.4 ( 0.05 )
    -0.3 ( 0.05 )
        Week 32
    -0.2 ( 0.06 )
    -0.2 ( 0.06 )
    -0.4 ( 0.06 )
    -0.3 ( 0.06 )
        Week 40
    -0.3 ( 0.06 )
    -0.2 ( 0.06 )
    -0.4 ( 0.06 )
    -0.3 ( 0.06 )
        Week 48 (End Treatment Period 2)
    -0.3 ( 0.06 )
    -0.2 ( 0.06 )
    -0.4 ( 0.06 )
    -0.3 ( 0.06 )
        FUP1 (Week 52)
    -0.4 ( 0.05 )
    -0.2 ( 0.05 )
    -0.4 ( 0.05 )
    -0.3 ( 0.05 )
        FUP2 (Week 56)
    -0.3 ( 0.05 )
    0.0 ( 0.05 )
    -0.1 ( 0.05 )
    -0.3 ( 0.05 )
        FUP 3 (Week 60)
    -0.2 ( 0.07 )
    -0.1 ( 0.06 )
    0.0 ( 0.07 )
    -0.2 ( 0.06 )
    No statistical analyses for this end point

    Secondary: Cohort 2: Change from Baseline in Immunoglobulin M (IgM) levels

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    End point title
    		 Cohort 2: Change from Baseline in Immunoglobulin M (IgM) levels
    End point description
    Plasma samples for Immunoglobulin M (IgM) were collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
    End point values
    		 Cohort 2: CFZ533 600 mg - CFZ533 600 mg Cohort 2: Placebo - CFZ533 300 mg
    Number of subjects analysed
    49
    47
    Units: g/L
    least squares mean (standard error)
        Week 4
    -0.1 ( 0.03 )
    0.0 ( 0.03 )
        Week 8
    -0.3 ( 0.04 )
    0.0 ( 0.04 )
        Week 12
    -0.3 ( 0.05 )
    0.0 ( 0.05 )
        Week 16
    -0.4 ( 0.05 )
    -0.1 ( 0.06 )
        Week 20
    -0.4 ( 0.06 )
    -0.1 ( 0.06 )
        Week 24 (End Treatment Period 1)
    -0.4 ( 0.06 )
    0.0 ( 0.06 )
        Week 28
    -0.5 ( 0.06 )
    -0.2 ( 0.06 )
        Week 32
    -0.5 ( 0.06 )
    -0.2 ( 0.07 )
        Week 40
    -0.5 ( 0.07 )
    -0.3 ( 0.07 )
        Week 48 (End Treatment Period 2)
    -0.5 ( 0.07 )
    -0.3 ( 0.07 )
        FUP1 (Week 52)
    -0.5 ( 0.06 )
    -0.3 ( 0.06 )
        FUP2 (Week 56)
    -0.5 ( 0.07 )
    -0.2 ( 0.72 )
        FUP 3 (Week 60)
    -0.5 ( 0.08 )
    -0.1 ( 0.08 )
    No statistical analyses for this end point

    Secondary: Cohort 1: Change from Baseline in plasma CXCL-13 levels

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    End point title
    		 Cohort 1: Change from Baseline in plasma CXCL-13 levels
    End point description
    Plasma samples for Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1) were collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 48 (End Treatment Period 2), FUP 3 (Week 60)
    End point values
    		 Cohort 1: CFZ533 300 mg - CFZ533 300 mg Cohort 1: Placebo - CFZ533 600 mg Cohort 1: CFZ533 150 mg - CFZ533 150 mg Cohort 1: CFZ533 600 mg - CFZ533 600 mg
    Number of subjects analysed
    41
    43
    40
    39
    Units: pg/mL
    least squares mean (standard error)
        Week 4
    -88.4 ( 12.74 )
    -19.0 ( 12.51 )
    -78.7 ( 12.84 )
    -77.0 ( 13.23 )
        Week 12
    -77.4 ( 12.59 )
    -23.8 ( 12.42 )
    -99.4 ( 12.56 )
    -108.5 ( 12.69 )
        Week 24 (End Treatment Period 1)
    -83.2 ( 13.98 )
    -15.6 ( 13.78 )
    -89.7 ( 14.08 )
    -111.6 ( 14.26 )
        Week 32
    -78.3 ( 18.21 )
    -102.5 ( 17.37 )
    -80.5 ( 17.68 )
    -71.3 ( 19.02 )
        Week 48 (End Treatment Period 2)
    -89.7 ( 12.26 )
    -116.6 ( 11.73 )
    -75.9 ( 12.02 )
    -118.7 ( 12.15 )
        FUP 3 (Week 60)
    -22.4 ( 22.55 )
    -73.9 ( 21.62 )
    24.4 ( 22.10 )
    -68.7 ( 22.24 )
    No statistical analyses for this end point

    Secondary: Cohort 2: Change from Baseline in plasma CXCL-13 levels

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    End point title
    		 Cohort 2: Change from Baseline in plasma CXCL-13 levels
    End point description
    Plasma samples for Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1) were collected and analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 48 (End Treatment Period 2), FUP 3 (Week 60)
    End point values
    		 Cohort 2: CFZ533 600 mg - CFZ533 600 mg Cohort 2: Placebo - CFZ533 300 mg
    Number of subjects analysed
    49
    45
    Units: pg/mL
    least squares mean (standard error)
        Week 4
    -88.7 ( 7.99 )
    -9.0 ( 8.50 )
        Week 12
    -97.8 ( 15.55 )
    8.8 ( 16.16 )
        Week 24 (End Treatment Period 1)
    -114.1 ( 6.81 )
    -27.4 ( 7.19 )
        Week 32
    -116.1 ( 6.65 )
    -97.2 ( 7.03 )
        Week 48 (End Treatment Period 2)
    -107.8 ( 6.81 )
    -99.2 ( 6.84 )
        FUP 3 (Week 60)
    -66.5 ( 10.53 )
    -10.9 ( 10.76 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment adverse events and deaths were reported from first dose of study treatment to 14 weeks after last dose of study medication, up to Week 60.
    Adverse event reporting additional description
    Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Cohort 1@Placebo@24 Weeks
    Reporting group description
    		 Cohort 1@Placebo@24 Weeks

    Reporting group title
    Cohort 1@CFZ533 600 mg@24 Weeks
    Reporting group description
    		 Cohort 1@CFZ533 600 mg@24 Weeks

    Reporting group title
    Cohort 1@CFZ533 150 mg@48 Weeks
    Reporting group description
    		 Cohort 1@CFZ533 150 mg@48 Weeks

    Reporting group title
    Cohort 1@CFZ533 300 mg@48 Weeks
    Reporting group description
    		 Cohort 1@CFZ533 300 mg@48 Weeks

    Reporting group title
    Cohort 1@CFZ533 600 mg@48 Weeks
    Reporting group description
    		 Cohort 1@CFZ533 600 mg@48 Weeks

    Reporting group title
    Cohort 2@Placebo@24 Weeks
    Reporting group description
    		 Cohort 2@Placebo@24 Weeks

    Reporting group title
    Cohort 2@CFZ533 300 mg@24 Weeks
    Reporting group description
    		 Cohort 2@CFZ533 300 mg@24 Weeks

    Reporting group title
    Cohort 2@CFZ533 600 mg@48 Weeks
    Reporting group description
    		 Cohort 2@CFZ533 600 mg@48 Weeks

    Serious adverse events
    		 Cohort 1@Placebo@24 Weeks Cohort 1@CFZ533 600 mg@24 Weeks Cohort 1@CFZ533 150 mg@48 Weeks Cohort 1@CFZ533 300 mg@48 Weeks Cohort 1@CFZ533 600 mg@48 Weeks Cohort 2@Placebo@24 Weeks Cohort 2@CFZ533 300 mg@24 Weeks Cohort 2@CFZ533 600 mg@48 Weeks
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 43 (2.33%)
    4 / 41 (9.76%)
    6 / 44 (13.64%)
    6 / 42 (14.29%)
    6 / 44 (13.64%)
    2 / 50 (4.00%)
    5 / 44 (11.36%)
    6 / 50 (12.00%)
         number of deaths (all causes)
    0
    0
    0
    1
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    1
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    1 / 44 (2.27%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Pelvic organ prolapse
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    1 / 50 (2.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Angle closure glaucoma
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Enteritis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salivary gland cyst
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Glomerulonephritis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Hand deformity
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sjogren's syndrome
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis bacterial
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    1 / 50 (2.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis aseptic
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    1 / 44 (2.27%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal abscess
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound abscess
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1@Placebo@24 Weeks Cohort 1@CFZ533 600 mg@24 Weeks Cohort 1@CFZ533 150 mg@48 Weeks Cohort 1@CFZ533 300 mg@48 Weeks Cohort 1@CFZ533 600 mg@48 Weeks Cohort 2@Placebo@24 Weeks Cohort 2@CFZ533 300 mg@24 Weeks Cohort 2@CFZ533 600 mg@48 Weeks
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 43 (41.86%)
    28 / 41 (68.29%)
    33 / 44 (75.00%)
    34 / 42 (80.95%)
    34 / 44 (77.27%)
    27 / 50 (54.00%)
    32 / 44 (72.73%)
    41 / 50 (82.00%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    3 / 44 (6.82%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    1 / 44 (2.27%)
    1 / 50 (2.00%)
         occurrences all number
    1
    0
    3
    0
    1
    0
    1
    1
    Immunisation reaction
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 41 (7.32%)
    1 / 44 (2.27%)
    3 / 42 (7.14%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences all number
    2
    4
    1
    3
    1
    0
    0
    0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    3 / 44 (6.82%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    0
    0
    Hypertension
         subjects affected / exposed
    4 / 43 (9.30%)
    0 / 41 (0.00%)
    2 / 44 (4.55%)
    0 / 42 (0.00%)
    2 / 44 (4.55%)
    3 / 50 (6.00%)
    2 / 44 (4.55%)
    2 / 50 (4.00%)
         occurrences all number
    4
    0
    2
    0
    3
    3
    2
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 43 (4.65%)
    0 / 41 (0.00%)
    2 / 44 (4.55%)
    3 / 42 (7.14%)
    4 / 44 (9.09%)
    2 / 50 (4.00%)
    2 / 44 (4.55%)
    0 / 50 (0.00%)
         occurrences all number
    2
    0
    2
    4
    6
    2
    9
    0
    Headache
         subjects affected / exposed
    5 / 43 (11.63%)
    1 / 41 (2.44%)
    9 / 44 (20.45%)
    6 / 42 (14.29%)
    8 / 44 (18.18%)
    5 / 50 (10.00%)
    4 / 44 (9.09%)
    3 / 50 (6.00%)
         occurrences all number
    6
    1
    16
    8
    15
    7
    4
    4
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    0 / 44 (0.00%)
    3 / 42 (7.14%)
    2 / 44 (4.55%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    2 / 50 (4.00%)
         occurrences all number
    0
    1
    0
    3
    4
    0
    0
    2
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 41 (2.44%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    1 / 50 (2.00%)
    1 / 44 (2.27%)
    3 / 50 (6.00%)
         occurrences all number
    1
    1
    1
    0
    1
    1
    1
    3
    Neutropenia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    5 / 42 (11.90%)
    2 / 44 (4.55%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    0
    0
    6
    4
    0
    0
    3
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    1 / 44 (2.27%)
    2 / 42 (4.76%)
    3 / 44 (6.82%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    1 / 50 (2.00%)
         occurrences all number
    0
    3
    3
    2
    4
    0
    0
    1
    Fatigue
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 41 (2.44%)
    5 / 44 (11.36%)
    1 / 42 (2.38%)
    3 / 44 (6.82%)
    0 / 50 (0.00%)
    1 / 44 (2.27%)
    2 / 50 (4.00%)
         occurrences all number
    1
    1
    5
    1
    5
    0
    1
    2
    Pyrexia
         subjects affected / exposed
    3 / 43 (6.98%)
    2 / 41 (4.88%)
    6 / 44 (13.64%)
    4 / 42 (9.52%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    2 / 44 (4.55%)
    4 / 50 (8.00%)
         occurrences all number
    3
    2
    6
    5
    0
    0
    2
    6
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    1 / 44 (2.27%)
    3 / 50 (6.00%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    2
    3
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    1 / 42 (2.38%)
    4 / 44 (9.09%)
    1 / 50 (2.00%)
    1 / 44 (2.27%)
    2 / 50 (4.00%)
         occurrences all number
    0
    0
    1
    1
    6
    1
    1
    2
    Abdominal pain upper
         subjects affected / exposed
    2 / 43 (4.65%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    4 / 42 (9.52%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    2 / 44 (4.55%)
    2 / 50 (4.00%)
         occurrences all number
    2
    0
    1
    6
    0
    0
    2
    2
    Diarrhoea
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 41 (2.44%)
    2 / 44 (4.55%)
    1 / 42 (2.38%)
    3 / 44 (6.82%)
    5 / 50 (10.00%)
    1 / 44 (2.27%)
    4 / 50 (8.00%)
         occurrences all number
    1
    1
    3
    1
    6
    6
    1
    4
    Nausea
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    2 / 44 (4.55%)
    1 / 42 (2.38%)
    2 / 44 (4.55%)
    3 / 50 (6.00%)
    1 / 44 (2.27%)
    4 / 50 (8.00%)
         occurrences all number
    0
    0
    2
    1
    4
    3
    1
    7
    Parotid gland enlargement
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    3 / 42 (7.14%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences all number
    0
    0
    0
    4
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    2 / 44 (4.55%)
    3 / 42 (7.14%)
    1 / 44 (2.27%)
    1 / 50 (2.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
         occurrences all number
    0
    0
    2
    3
    1
    1
    0
    0
    Cough
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 41 (2.44%)
    3 / 44 (6.82%)
    3 / 42 (7.14%)
    2 / 44 (4.55%)
    2 / 50 (4.00%)
    1 / 44 (2.27%)
    3 / 50 (6.00%)
         occurrences all number
    1
    1
    3
    3
    3
    2
    1
    4
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    3 / 44 (6.82%)
    2 / 50 (4.00%)
    0 / 44 (0.00%)
    3 / 50 (6.00%)
         occurrences all number
    0
    1
    0
    0
    4
    2
    0
    3
    Rash
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 41 (4.88%)
    1 / 44 (2.27%)
    2 / 42 (4.76%)
    1 / 44 (2.27%)
    4 / 50 (8.00%)
    0 / 44 (0.00%)
    6 / 50 (12.00%)
         occurrences all number
    0
    3
    1
    2
    1
    5
    0
    7
    Pruritus
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    3 / 50 (6.00%)
    0 / 44 (0.00%)
    3 / 50 (6.00%)
         occurrences all number
    1
    0
    1
    0
    1
    3
    0
    4
    Eczema
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    2 / 44 (4.55%)
    1 / 42 (2.38%)
    3 / 44 (6.82%)
    2 / 50 (4.00%)
    1 / 44 (2.27%)
    3 / 50 (6.00%)
         occurrences all number
    0
    0
    3
    1
    3
    2
    1
    4
    Endocrine disorders
    Thyroid mass
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 44 (0.00%)
    0 / 50 (0.00%)
    1 / 44 (2.27%)
    3 / 50 (6.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 43 (9.30%)
    2 / 41 (4.88%)
    6 / 44 (13.64%)
    2 / 42 (4.76%)
    5 / 44 (11.36%)
    4 / 50 (8.00%)
    5 / 44 (11.36%)
    5 / 50 (10.00%)
         occurrences all number
    5
    4
    7
    2
    8
    4
    6
    6
    Back pain
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 41 (4.88%)
    4 / 44 (9.09%)
    3 / 42 (7.14%)
    1 / 44 (2.27%)
    3 / 50 (6.00%)
    6 / 44 (13.64%)
    6 / 50 (12.00%)
         occurrences all number
    1
    2
    4
    4
    1
    3
    6
    7
    Neck pain
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    3 / 44 (6.82%)
    0 / 50 (0.00%)
    2 / 44 (4.55%)
    0 / 50 (0.00%)
         occurrences all number
    0
    0
    1
    0
    3
    0
    2
    0
    Myalgia
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 41 (2.44%)
    1 / 44 (2.27%)
    3 / 42 (7.14%)
    2 / 44 (4.55%)
    1 / 50 (2.00%)
    1 / 44 (2.27%)
    4 / 50 (8.00%)
         occurrences all number
    1
    1
    1
    3
    3
    2
    2
    5
    Pain in extremity
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    1 / 44 (2.27%)
    1 / 42 (2.38%)
    3 / 44 (6.82%)
    1 / 50 (2.00%)
    2 / 44 (4.55%)
    4 / 50 (8.00%)
         occurrences all number
    1
    0
    2
    2
    3
    1
    2
    5
    Infections and infestations
    COVID-19
         subjects affected / exposed
    2 / 43 (4.65%)
    10 / 41 (24.39%)
    10 / 44 (22.73%)
    11 / 42 (26.19%)
    11 / 44 (25.00%)
    8 / 50 (16.00%)
    8 / 44 (18.18%)
    20 / 50 (40.00%)
         occurrences all number
    2
    10
    11
    11
    13
    8
    8
    22
    Conjunctivitis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    3 / 50 (6.00%)
    2 / 44 (4.55%)
    1 / 50 (2.00%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    2
    1
    Herpes simplex
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    4 / 44 (9.09%)
    0 / 42 (0.00%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    3 / 50 (6.00%)
         occurrences all number
    1
    0
    5
    0
    1
    0
    0
    3
    Influenza
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 41 (7.32%)
    2 / 44 (4.55%)
    4 / 42 (9.52%)
    2 / 44 (4.55%)
    0 / 50 (0.00%)
    2 / 44 (4.55%)
    1 / 50 (2.00%)
         occurrences all number
    0
    3
    2
    5
    3
    0
    2
    1
    Pneumonia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    2 / 44 (4.55%)
    1 / 42 (2.38%)
    1 / 44 (2.27%)
    0 / 50 (0.00%)
    0 / 44 (0.00%)
    3 / 50 (6.00%)
         occurrences all number
    0
    0
    2
    1
    2
    0
    0
    3
    Oral herpes
         subjects affected / exposed
    2 / 43 (4.65%)
    0 / 41 (0.00%)
    3 / 44 (6.82%)
    2 / 42 (4.76%)
    5 / 44 (11.36%)
    1 / 50 (2.00%)
    4 / 44 (9.09%)
    1 / 50 (2.00%)
         occurrences all number
    2
    0
    4
    4
    11
    1
    4
    2
    Nasopharyngitis
         subjects affected / exposed
    2 / 43 (4.65%)
    6 / 41 (14.63%)
    5 / 44 (11.36%)
    8 / 42 (19.05%)
    9 / 44 (20.45%)
    3 / 50 (6.00%)
    3 / 44 (6.82%)
    6 / 50 (12.00%)
         occurrences all number
    2
    6
    8
    13
    11
    6
    4
    6
    Rhinitis
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 41 (2.44%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    2 / 44 (4.55%)
    2 / 50 (4.00%)
    1 / 44 (2.27%)
    5 / 50 (10.00%)
         occurrences all number
    1
    1
    0
    0
    2
    2
    2
    6
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 43 (2.33%)
    4 / 41 (9.76%)
    3 / 44 (6.82%)
    3 / 42 (7.14%)
    1 / 44 (2.27%)
    1 / 50 (2.00%)
    3 / 44 (6.82%)
    6 / 50 (12.00%)
         occurrences all number
    1
    4
    4
    3
    1
    2
    4
    11
    Sinusitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    1 / 44 (2.27%)
    2 / 42 (4.76%)
    1 / 44 (2.27%)
    2 / 50 (4.00%)
    1 / 44 (2.27%)
    4 / 50 (8.00%)
         occurrences all number
    0
    1
    1
    2
    1
    2
    1
    4
    Urinary tract infection
         subjects affected / exposed
    2 / 43 (4.65%)
    3 / 41 (7.32%)
    3 / 44 (6.82%)
    4 / 42 (9.52%)
    5 / 44 (11.36%)
    0 / 50 (0.00%)
    4 / 44 (9.09%)
    8 / 50 (16.00%)
         occurrences all number
    3
    5
    5
    4
    10
    0
    5
    12

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Feb 2020
    Amendment 1: Introduction of screening for human cytomegalovirus (CMV) and monitoring for active CMV infection in at risk subjects.
    27 Apr 2021
    Amendment 2: Introduction of an interim analysis to assess the dose response relationship of iscalimab, after at least 50% of the subjects in Cohort 1 have completed Week 24 visit or discontinued prior to that. The results from the interim analysis may inform future clinical development planning.

    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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