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    Clinical Trial Results:
    A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study to Evaluate the Efficacy and Safety of VIB4920 in subjects with Sjögren’s Syndrome (SS)

    Summary
    EudraCT number
    		 2019-002713-19
    Trial protocol
    		 GB   PL   HU   IT  
    Global end of trial date
    10 Mar 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Mar 2024
    First version publication date
    23 Mar 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    VIB4920.P2.S2
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04129164
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND number: 128905
    Sponsors
    Sponsor organisation name
    Horizon Therapeutics USA, Inc.
    Sponsor organisation address
    1 Horizon Way, Deerfield, United States, 60015-3888
    Public contact
    Medical director, Horizon Therapeutics USA, Inc., clinicaltrials@horizontherapeutics.com
    Scientific contact
    Medical director, Horizon Therapeutics USA, Inc., clinicaltrials@horizontherapeutics.com
    Sponsor organisation name
    Horizon Therapeutics USA, Inc.
    Sponsor organisation address
    1 Horizon Way , Deerfield, United States, 60015-3888
    Public contact
    Medical director, Horizon Therapeutics USA, Inc., clinicaltrials@horizontherapeutics.com
    Scientific contact
    Medical director, Horizon Therapeutics USA, Inc., clinicaltrials@horizontherapeutics.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
    10 Mar 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Mar 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Population #1: To evaluate the clinical efficacy of multiple doses of VIB4920 (Dazodalibep) in glandular and extraglandular manifestations of SS patients with moderate to high systemic disease activity. Population #2: To evaluate the clinical efficacy of multiple doses of VIB4920 in the key subjective complaints of SS (dryness, fatigue, pain).
    Protection of trial subjects
    The study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Council for Harmonisation (ICH)/Good Clinical Practice (GCP), applicable regulatory requirements, and the Sponsor’s policy on Ethical Interactions. Written and/or oral information about the nature, purpose, possible risk, and benefit of the study was provided to all participants in a language understandable by the participants. Participants were also notified that they were free to discontinue from the study at any time. Written informed consent was obtained from each participant before any study procedures or assessments were performed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Nov 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
    Poland: 50
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    France: 9
    Country: Number of subjects enrolled
    Hungary: 7
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Peru: 25
    Country: Number of subjects enrolled
    Korea, Republic of: 7
    Country: Number of subjects enrolled
    Taiwan: 8
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    United States: 49
    Country: Number of subjects enrolled
    Mexico: 23
    Worldwide total number of subjects
    183
    EEA total number of subjects
    67
    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)
    162
    From 65 to 84 years
    21
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Population #1 will be composed of subjects with moderate to severe systemic disease activity defined by ESSDAI ≥ 5. Population #2 will be composed of subjects with mild systemic disease activity defined by ESSDAI score < 5 but with moderate to severe subjective symptoms defined by ESSPRI score ≥ 5 and residual stimulated salivary flow.

    Pre-assignment
    Screening details
    		 Sjogren syndrome subjects meeting the 2016 ACR/EULAR classification criteria and the inclusion/exclusion criteria were enrolled in this study. Randomization were stratified by ESSDAI score at screening (< 10 points vs ≥ 10 points) for Population 1 and by ESSPRI score at screening (< 7.5 points vs ≥ 7.5 points) for Population 2.

    Period 1
    Period 1 title
    Stage 1
    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
    		 Placebo Population 1
    Arm description
    		 Subjects with moderate to severe systemic disease activity received placebo by intravenous (IV) infusion, once every two weeks (Q2W) for three doses and then once every four weeks (Q4W) for 4 additional doses.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo was administered by intravenous infusion following dilution in normal saline.

    Arm title
    		 Dazodalibep Population 1
    Arm description
    		 Subjects with moderate to severe systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dazodalibep
    Investigational medicinal product code
    Other name
    VIB4920
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dazodalibep 1500 mg was administered by intravenous infusion following dilution in normal saline.

    Arm title
    		 Placebo Population 2
    Arm description
    		 Subjects with low systemic disease activity received placebo by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo was administered by intravenous infusion.

    Arm title
    		 Dazodalibep Population 2
    Arm description
    		 Subjects with low systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    VIB4920
    Investigational medicinal product code
    Other name
    Dazodalibep
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dazodalibep 1500 mg was administered by intravenous infusion following dilution in normal saline.

    Number of subjects in period 1
    		Placebo Population 1 Dazodalibep Population 1 Placebo Population 2 Dazodalibep Population 2
    Started
    38
    36
    55
    54
    Completed
    37
    34
    52
    50
    Not completed
    1
    2
    3
    4
         Adverse event, serious fatal
    -
    1
    -
    -
         Consent withdrawn by subject
    1
    1
    1
    4
         Adverse event, non-fatal
    -
    -
    2
    -
    Period 2
    Period 2 title
    Stage 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
    Yes

    Arm title
    		 Placebo to dazodalibep Population 1
    Arm description
    		 Subjects with moderate to severe systemic disease activity who received placebo in stage 1, received dazodalibep 1500 mg by IV infusion, Q4W for five doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dazodalibep
    Investigational medicinal product code
    Other name
    VIB4920
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dazodalibep 1500 mg was administered by intravenous infusion following dilution in normal saline.

    Arm title
    		 Dazodalibep to Placebo Population 1
    Arm description
    		 Subjects with moderate to severe systemic disease activity who received dazodalibep in stage 1, received placebo, Q4W for five doses.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo was administered by intravenous infusion following dilution in normal saline.

    Arm title
    		 Placebo to dazodalibep Population 2
    Arm description
    		 Subjects with low systemic disease activity who received placebo in stage 1, received dazodalibep 1500 mg by IV infusion, Q4W for five doses in stage 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dazodalibep
    Investigational medicinal product code
    Other name
    VIB4920
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dazodalibep 1500 mg was administered by intravenous infusion following dilution in normal saline.

    Arm title
    		 Dazodalibep to placebo Population 2
    Arm description
    		 Subjects with low systemic disease activity who received dazodalibep in stage 1, received placebo by IV infusion, Q4W for five doses in stage 2.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo was administered by intravenous infusion following dilution in normal saline.

    Number of subjects in period 2
    		Placebo to dazodalibep Population 1 Dazodalibep to Placebo Population 1 Placebo to dazodalibep Population 2 Dazodalibep to placebo Population 2
    Started
    37
    34
    52
    50
    Completed
    35
    32
    47
    47
    Not completed
    2
    2
    5
    3
         Consent withdrawn by subject
    2
    1
    3
    2
         Miscellaneous
    -
    -
    2
    -
         Pregnancy
    -
    -
    -
    1
         Lost to follow-up
    -
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo Population 1
    Reporting group description
    		 Subjects with moderate to severe systemic disease activity received placebo by intravenous (IV) infusion, once every two weeks (Q2W) for three doses and then once every four weeks (Q4W) for 4 additional doses.

    Reporting group title
    Dazodalibep Population 1
    Reporting group description
    		 Subjects with moderate to severe systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.

    Reporting group title
    Placebo Population 2
    Reporting group description
    		 Subjects with low systemic disease activity received placebo by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.

    Reporting group title
    Dazodalibep Population 2
    Reporting group description
    		 Subjects with low systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.

    Reporting group values
    		 Placebo Population 1 Dazodalibep Population 1 Placebo Population 2 Dazodalibep Population 2 Total
    Number of subjects
    		 38 36 55 54 183
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 48.8 ± 12.1 51.7 ± 9.6 49.0 ± 12.6 50.9 ± 11.7 -
    Gender categorical
    Units: Subjects
        Female
    		 38 35 50 53 176
        Male
    		 0 1 5 1 7
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 4 11 9 25
        Asian
    		 0 2 5 11 18
        Black or African American
    		 1 3 3 4 11
        White
    		 34 26 31 23 114
        Other
    		 2 1 5 7 15
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 8 8 23 22 61
        Not Hispanic or Latino
    		 30 28 32 32 122
    ESSDAI total score
    ESSDAI grades disease activity in 12 domains (cutaneous, respiratory, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathic, and biological). The weights of each domain were obtained by multiple regression modeling, using the Physician’s Global Assessment of Activity as gold standard. Each domain is weighted from 1 (Biologic domain) to 6 (Muscular domain) and has 3 or 4 levels of activity per domain, ranging from 0 (no activity) to 3 (high activity). The theoretical range of values for the ESSDAI is 0 to 123
    Units: Score on a scale
        arithmetic mean (standard deviation)
    		 10.1 ± 4.1 11.4 ± 4.5 2.5 ± 1.6 3.1 ± 1.8 -
    ESSPRI total score
    ESSPRI is a self-evaluation tool that was developed in a multicenter international cohort of 230 patients. The ESSPRI uses a 0 to 10 numerical analog scale (ranging from 0 [no symptoms] to 10 [maximal imaginable severity]), one for the assessment of each of the 3 domains: dryness, fatigue, and pain (articular and/or muscular). The weights of the domains are identical, and the mean of the scores of the 3 domains represents the final score. The recall period was stated in each question as “the last 2 weeks.” The instrument was completed in approximately 1 minute.
    Units: Score on a scale
        arithmetic mean (standard deviation)
    		 6.6 ± 1.8 6.6 ± 1.6 6.8 ± 1.2 7.1 ± 1.6 -

    End points

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    End points reporting groups
    Reporting group title
    Placebo Population 1
    Reporting group description
    		 Subjects with moderate to severe systemic disease activity received placebo by intravenous (IV) infusion, once every two weeks (Q2W) for three doses and then once every four weeks (Q4W) for 4 additional doses.

    Reporting group title
    Dazodalibep Population 1
    Reporting group description
    		 Subjects with moderate to severe systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.

    Reporting group title
    Placebo Population 2
    Reporting group description
    		 Subjects with low systemic disease activity received placebo by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.

    Reporting group title
    Dazodalibep Population 2
    Reporting group description
    		 Subjects with low systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.
    Reporting group title
    Placebo to dazodalibep Population 1
    Reporting group description
    		 Subjects with moderate to severe systemic disease activity who received placebo in stage 1, received dazodalibep 1500 mg by IV infusion, Q4W for five doses.

    Reporting group title
    Dazodalibep to Placebo Population 1
    Reporting group description
    		 Subjects with moderate to severe systemic disease activity who received dazodalibep in stage 1, received placebo, Q4W for five doses.

    Reporting group title
    Placebo to dazodalibep Population 2
    Reporting group description
    		 Subjects with low systemic disease activity who received placebo in stage 1, received dazodalibep 1500 mg by IV infusion, Q4W for five doses in stage 2.

    Reporting group title
    Dazodalibep to placebo Population 2
    Reporting group description
    		 Subjects with low systemic disease activity who received dazodalibep in stage 1, received placebo by IV infusion, Q4W for five doses in stage 2.

    Subject analysis set title
    Placebo - Dazodalibep 1500mg Population 1 - PK Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects with moderate to severe systemic disease activity received placebo by intravenous (IV) infusion, once every two weeks (Q2W) for three doses and then once every four weeks (Q4W) for 4 additional doses during stage 1 and received dazodalibep 1500 mg by IV infusion, Q4W for five doses during stage 2.

    Subject analysis set title
    Dazodalibep 1500mg - Placebo Population 1 - PK Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects with moderate to severe systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses during stage 1 and received placebo, Q4W for five doses during stage 2.

    Subject analysis set title
    Placebo - Dazodalibep 1500mg Population 2 - PK Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects with low systemic disease activity received placebo by IV infusion, Q2W for three doses and then Q4W for 4 additional doses during stage 1 and received dazodalibep 1500 mg by IV infusion, Q4W for five doses in stage 2.

    Subject analysis set title
    Dazodalibep 1500mg - Placebo Population 2 - PK Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects with low systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses during stage 1 and received placebo by IV infusion, Q4W for five doses in stage 2.

    Subject analysis set title
    Placebo to Dazodalibep 1500mg - Population 1 - VIB4920 Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects with moderate to severe systemic disease activity received placebo by IV infusion, Q2W for three doses and then Q4W for 4 additional doses in stage 1 and dazodalibep 1500 mg in stage 2 by IV infusion, Q4W for five doses.

    Subject analysis set title
    Dazodalibep 1500mg to Placebo - Population 1 - VIB4920 Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects with moderate to severe systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses in stage 1 and placebo in stage 2 by IV infusion, Q4W for five doses.

    Subject analysis set title
    Placebo to Dazodalibep 1500 mg - Population 2 - VIB4920 Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects with low systemic disease activity received placebo by IV infusion, Q2W for three doses and then Q4W for 4 additional doses in stage 1 and dazodalibep 1500 mg by IV infusion, Q4W for five doses in stage 2.

    Subject analysis set title
    Dazodalibep 1500mg to Placebo - Population 2 - VIB4920 Set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects with low systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses in stage 1 and placebo by IV infusion, Q4W for five doses in stage 2.

    Primary: Change From Baseline in EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) - Population 1

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    End point title
    		 Change From Baseline in EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) - Population 1 [1]
    End point description
    The ESSDAI is a systemic disease activity index that includes organ-by-organ definitions of disease activity. The ESSDAI grades disease activity in 12 domains (cutaneous, respiratory, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathic, and biological). The weights of each domain were obtained by multiple regression modeling, using the Physician’s Global Assessment of Activity as gold standard. Each domain is weighted from 1 (Biologic domain) to 6 (Muscular domain) and has 3 or 4 levels of activity per domain, ranging from 0 (no activity) to 3 (high activity). The theoretical range of values for the ESSDAI is 0 to 123, with the final score being calculated as follows: Final Score = Sum of all 12 domain scores Domain score = Activity level × Domain weight Analysis Population: The full analysis set (FAS) includes all randomized subjects who received any dose of investigational product.
    End point type
    Primary
    End point timeframe
    Baseline, day 169
    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 planned for only population 1 as primary endpoint
    End point values
    		 Placebo Population 1 Dazodalibep Population 1
    Number of subjects analysed
    36
    33
    Units: Score on a scale
        least squares mean (standard error)
    -4.1 ± 0.6
    -6.3 ± 0.6
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Dazodalibep Population 1 v Placebo Population 1
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.0167 [3]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -2.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -3.6
         upper limit
    		 -0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.9
    Notes
    [2] - Mixed-effect model for repeated measures (MMRM)
    [3] - MMRM analysis with treatment, visit, visit by treatment interaction, and baseline ESSDAI score included in the model. LSMean difference is VIB4920-placebo, with associated 90% confidence interval and p-value. Differences less than 0 favor dazodalibep

    Primary: Change From Baseline in EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) - Population 2

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    End point title
    		 Change From Baseline in EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) - Population 2 [4]
    End point description
    ESSPRI is a self-evaluation tool that was developed in a multicenter international cohort of 230 patients. The ESSPRI uses a 0 to 10 numerical analog scale (ranging from 0 [no symptoms] to 10 [maximal imaginable severity]), one for the assessment of each of the 3 domains: dryness, fatigue, and pain (articular and/or muscular). The weights of the domains are identical, and the mean of the scores of the 3 domains represents the final score. The recall period was stated in each question as “the last 2 weeks.” The instrument was completed in approximately 1 minute. Analysis Population: FAS population with available data at specified time point.
    End point type
    Primary
    End point timeframe
    Baseline, day 169
    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 planned for only population 2 as primary endpoint
    End point values
    		 Placebo Population 2 Dazodalibep Population 2
    Number of subjects analysed
    53
    51
    Units: Score on a scale
        least squares mean (standard error)
    -0.53 ± 0.23
    -1.80 ± 0.23
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Dazodalibep Population 2 v Placebo Population 2
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.0002
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -1.27
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.82
         upper limit
    		 -0.73
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.33
    Notes
    [5] - MMRM analysis with treatment, visit, visit by treatment interaction, randomization factor, and the baseline ESSPRI score included in the model. LSMean difference is Dazodalibep-placebo, with associated 90% confidence interval & p-value. Differences less than 0 favor dazodalibep

    Secondary: Change From Baseline in ESSPRI - Population 1

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    End point title
    		 Change From Baseline in ESSPRI - Population 1 [6]
    End point description
    ESSPRI is a self-evaluation tool that was developed in a multicenter international cohort of 230 patients. The ESSPRI uses a 0 to 10 numerical analog scale (ranging from 0 [no symptoms] to 10 [maximal imaginable severity]), one for the assessment of each of the 3 domains: dryness, fatigue, and pain (articular and/or muscular). The weights of the domains are identical, and the mean of the scores of the 3 domains represents the final score. The recall period was stated in each question as “the last 2 weeks.” The instrument was completed in approximately 1 minute. Analysis Population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, day 169
    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 planned for only population 1 as secondary endpoint
    End point values
    		 Placebo Population 1 Dazodalibep Population 1
    Number of subjects analysed
    36
    33
    Units: Score on a scale
        least squares mean (standard error)
    -1.12 ± 0.29
    -1.80 ± 0.31
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Dazodalibep Population 1 v Placebo Population 1
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.111 [7]
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.68
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.39
         upper limit
    		 0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.42
    Notes
    [7] - MMRM analysis with treatment, visit, visit by treatment interaction, and baseline ESSDAI score included in the model. LSMean difference is VIB4920-placebo, with associated 90% confidence interval & p-value. Differences less than 0 favor dazodalibep.

    Secondary: Percentage of Subjects Achieving ESSDAI[3] and ESSDAI[4] Response - Population 1

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    End point title
    		 Percentage of Subjects Achieving ESSDAI[3] and ESSDAI[4] Response - Population 1 [8]
    End point description
    ESSDAI is a systemic disease activity index that includes organ-by-organ definitions of disease activity. ESSDAI grades disease activity in 12 domains (cutaneous, respiratory, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathic, and biological). Weights of each domain were obtained by multiple regression modeling, using Physician’s Global Assessment of Activity as gold standard. Each domain is weighted from 1 (Biologic domain) to 6 (Muscular domain) and has 3 or 4 levels of activity per domain, ranging from 0 (no activity) to 3 (high activity). Theoretical range of values for ESSDAI is 0 to 123. Final score being calculated as follows: Final Score = Sum of all 12 domain scores Domain score = Activity level × Domain weight ESSDAI[3] and ESSDAI[4] response: Decrease of at least 3 and 4 points respectively from baseline in the ESSDAI. FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Day 169
    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 planned for only population 1 as secondary endpoint
    End point values
    		 Placebo Population 1 Dazodalibep Population 1
    Number of subjects analysed
    37
    36
    Units: Percentage of participants
    number (confidence interval 90%)
        ESSDAI[3]
    61.2 (47.2 to 73.6)
    72.3 (58.2 to 83.0)
        ESSDAI[4]
    50.9 (36.9 to 64.8)
    67.2 (52.4 to 79.2)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    ESSDAI[3]
    Comparison groups
    Dazodalibep Population 1 v Placebo Population 1
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3283 [9]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 3.8
    Notes
    [9] - Logistic regression analysis with treatment and baseline ESSDAI score included in the model. Odds ratio is VIB4920/placebo, with associated 90% confidence interval and p-value. Odds ratios greater than 1 favor dazodalibep.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    ESSDAI[4]
    Comparison groups
    Dazodalibep Population 1 v Placebo Population 1
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1823 [10]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 4.6
    Notes
    [10] - Logistic regression analysis with treatment and baseline ESSDAI score included in the model. Odds ratio is VIB4920/placebo, with associated 90% confidence interval and p-value. Odds ratios greater than 1 favor dazodalibep.

    Secondary: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue score - Population 1

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    End point title
    		 Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue score - Population 1 [11]
    End point description
    The FACIT-Fatigue is a 13-item questionnaire, subject-completed, used to assess the impact of fatigue. Its recall period is 7 days. The responses range from 0 (Not at all) to 4 (Very Much). To calculate the total score, the negatively stated items are reversed by subtracting the response from “4”. Final scores are the sum of the responses and range from 0 to 52. Higher scores indicate better QoL. It takes 5-10 minutes to complete. Analysis population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, day 169
    Notes
    [11] - 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 planned for population 1 and 2 as separate secondary endpoints
    End point values
    		 Placebo Population 1 Dazodalibep Population 1
    Number of subjects analysed
    36
    33
    Units: Score on a scale
        least squares mean (standard error)
    5.8 ± 1.6
    8.1 ± 1.6
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Dazodalibep Population 1 v Placebo Population 1
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    P-value
    		 = 0.3028
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    2.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 6.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.3
    Notes
    [12] - MMRM analysis with treatment, visit, visit by treatment interaction, randomization stratification factor and baseline FACIT score included in the model. LSMean difference is VIB4920-placebo, with associated 90% confidence interval and p-value. Differences greater than 0 favor dazodalibep.

    Secondary: Change from baseline in Ocular Surface Disease Index (OSDI) - Population 1

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    End point title
    		 Change from baseline in Ocular Surface Disease Index (OSDI) - Population 1 [13]
    End point description
    OSDI is a valid and reliable instrument for assessing effect on vision-related function and dry eye disease severity (normal, mild, moderate, and severe). Its recall period is 1 week. It is composed of 12 questions that the physician asks the subject and circles the number that best represents each question. The responses for each question range from 0 (None of the time) to 4 (All of the time). The OSDI score is calculated as (sum of scores for questions answered)/(number of questions answered)×25, which ranges from 0 to 100 with higher scores signifying greater disability. The assessment can be completed in 5 minutes. Analysis population FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, day 169
    Notes
    [13] - 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 planned for population 1 and 2 as separate secondary endpoints
    End point values
    		 Placebo Population 1 Dazodalibep Population 1
    Number of subjects analysed
    35
    31
    Units: Score on a scale
        least squares mean (standard error)
    -14.02 ± 3.06
    -16.00 ± 3.22
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Dazodalibep Population 1 v Placebo Population 1
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [14]
    P-value
    		 = 0.6583
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    0.6583
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -9.38
         upper limit
    		 5.44
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.44
    Notes
    [14] - MMRM analysis with treatment, visit, visit by treatment interaction, randomization stratification factor and baseline OSDI score included in the model. LSMean difference is VIB4920-placebo, with associated 90% CI and p-value. Differences less than 0 favor dazodalibep.

    Secondary: Change from Baseline in PGIS Scale - Population 1

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    End point title
    		 Change from Baseline in PGIS Scale - Population 1 [15]
    End point description
    The PGIS is a single item designed to capture the subject’s perception of overall symptom severity over the past week on a 5-point categorical response scale (none, mild, moderate, severe, or very severe). Analysis population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, day 169
    Notes
    [15] - 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 planned for population 1 and 2 as separate secondary endpoints
    End point values
    		 Placebo Population 1 Dazodalibep Population 1
    Number of subjects analysed
    36
    33
    Units: Score on a scale
        least squares mean (standard error)
    -0.5 ± 0.1
    -0.6 ± 0.1
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Dazodalibep Population 1 v Placebo Population 1
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [16]
    P-value
    		 = 0.3629
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Notes
    [16] - MMRM analysis with treatment, visit, visit by treatment interaction, randomization stratification factor and baseline PGIS score included in the model. LSMean difference is VIB4920-placebo, with associated 90% CI and p-value. Differences less than 0 favor dazodalibep.

    Secondary: Percentage of Subjects Achieving ESSPRI response - Population 2

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    End point title
    		 Percentage of Subjects Achieving ESSPRI response - Population 2 [17]
    End point description
    ESSPRI is a self-evaluation tool that was developed in a multicenter international cohort of 230 patients. The ESSPRI uses a 0 to 10 numerical analog scale (ranging from 0 [no symptoms] to 10 [maximal imaginable severity]), one for the assessment of each of the 3 domains: dryness, fatigue, and pain (articular and/or muscular). The weights of the domains are identical, and the mean of the scores of the 3 domains represents the final score. The recall period was stated in each question as “the last 2 weeks.” The instrument was completed in approximately 1 minute. ESSPRI response, defined as ≥ 1 point or 15% reduction from baseline in ESSPRI score at Day 169 without premature discontinuation from the study and without receiving rescue therapy. Analysis population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Day 169
    Notes
    [17] - 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 planned for population 2 as secondary endpoint
    End point values
    		 Placebo Population 2 Dazodalibep Population 2
    Number of subjects analysed
    55
    54
    Units: Percentage of participants
        number (confidence interval 90%)
    33.2 (23.6 to 44.4)
    66.4 (54.9 to 76.2)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Dazodalibep Population 2 v Placebo Population 2
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    P-value
    		 = 0.0008
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 2
         upper limit
    		 7.8
    Notes
    [18] - logistic regression analysis with treatment and baseline ESSPRI score included in the model. Odds ratio is Dazodalibep/placebo, with associated 90% confidence interval and p-value. Odds ratios greater than 1 favor dazodalibep.

    Secondary: Change From Baseline in FACIT-Fatigue Score - Population 2

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    End point title
    		 Change From Baseline in FACIT-Fatigue Score - Population 2 [19]
    End point description
    The FACIT-Fatigue is a 13-item questionnaire, subject-completed, used to assess the impact of fatigue. Its recall period is 7 days. The responses range from 0 (Not at all) to 4 (Very Much). To calculate the total score, the negatively stated items are reversed by subtracting the response from “4”. Final scores are the sum of the responses and range from 0 to 52. Higher scores indicate better QoL. It takes 5-10 minutes to complete. Analysis population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, day 169
    Notes
    [19] - 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 planned for population 1 and 2 as separate secondary endpoints
    End point values
    		 Placebo Population 2 Dazodalibep Population 2
    Number of subjects analysed
    52
    51
    Units: Score on a scale
        least squares mean (standard error)
    2.8 ± 1.4
    8.1 ± 1.4
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Dazodalibep Population 2 v Placebo Population 2
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    P-value
    		 = 0.0095
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    5.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 2
         upper limit
    		 8.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    2
    Notes
    [20] - MMRM analysis with treatment, visit, visit by treatment interaction, randomization stratification factor and baseline FACIT score included in the model. LSMean difference is Dazodalibep-placebo, with associated 90% confidence interval and p-value. Differences greater than 0 favor dazodalibep.

    Secondary: Change From Baseline in OSDI - Population 2

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    End point title
    		 Change From Baseline in OSDI - Population 2 [21]
    End point description
    OSDI is a valid and reliable instrument for assessing effect on vision-related function and dry eye disease severity (normal, mild, moderate, and severe). Its recall period is 1 week. It is composed of 12 questions that the physician asks the subject and circles the number that best represents each question. The responses for each question range from 0 (None of the time) to 4 (All of the time). The OSDI score is calculated as (sum of scores for questions answered)/(number of questions answered)×25, which ranges from 0 to 100 with higher scores signifying greater disability. The assessment can be completed in 5 minutes. Analysis population FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, day 169
    Notes
    [21] - 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 planned for population 1 and 2 as separate secondary endpoints
    End point values
    		 Placebo Population 2 Dazodalibep Population 2
    Number of subjects analysed
    50
    51
    Units: Score on a scale
        least squares mean (standard error)
    -8.52 ± 2.94
    -13.95 ± 2.95
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Dazodalibep Population 2 v Placebo Population 2
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [22]
    P-value
    		 = 0.1936
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -5.43
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -12.31
         upper limit
    		 1.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.15
    Notes
    [22] - MMRM analysis with treatment, visit, visit by treatment interaction, randomization stratification factor and baseline OSDI score included in the model. LSMean difference is Dazodalibep-placebo, with associated 90% confidence interval and p-value. Differences less than 0 favor dazodalibep.

    Secondary: Change From Baseline in PGIS - Population 2

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    End point title
    		 Change From Baseline in PGIS - Population 2 [23]
    End point description
    The PGIS is a single item designed to capture the subject’s perception of overall symptom severity over the past week on a 5-point categorical response scale (none, mild, moderate, severe, or very severe). Analysis population: FAS population with available data at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, day 169
    Notes
    [23] - 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 planned for population 1 and 2 as separate secondary endpoints
    End point values
    		 Placebo Population 2 Dazodalibep Population 2
    Number of subjects analysed
    52
    51
    Units: Score on a scale
        least squares mean (standard error)
    -0.4 ± 0.1
    -0.6 ± 0.1
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Dazodalibep Population 2 v Placebo Population 2
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [24]
    P-value
    		 = 0.1781
    Method
    		 MMRM
    Parameter type
    		 LSMean difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Notes
    [24] - MMRM analysis with treatment, visit, visit by treatment interaction, randomization stratification factor and baseline PGIS score included in the model. LSMean difference is Dazodalibep-placebo, with associated 90% confidence interval and p-value. Differences less than 0 favor Dazodalibep.

    Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) - Population 1 and 2

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    End point title
    		 Number of Participants With Treatment Emergent Adverse Events (TEAEs) - Population 1 and 2
    End point description
    An adverse event is any untoward medical occurrence associated with the use of an intervention in humans whether or not it is considered intervention-related. If an adverse event onset is on or after the first dose of IP administration, the AE was considered as a TEAE. Otherwise, the AE will be considered as a non-treatment emergent AE. Analysis population: The safety analysis set included all subjects who received any dose of IP. Subjects were analyzed according to the treatment that they actually received.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug until end of the study (Up to 365 days)
    End point values
    		 Placebo Population 1 Dazodalibep Population 1 Placebo Population 2 Dazodalibep Population 2 Placebo to dazodalibep Population 1 Dazodalibep to Placebo Population 1 Placebo to dazodalibep Population 2 Dazodalibep to placebo Population 2
    Number of subjects analysed
    38
    36
    55
    54
    37
    34
    52
    49
    Units: Participants
    23
    28
    38
    37
    28
    25
    34
    32
    No statistical analyses for this end point

    Secondary: Serum Concentrations of Dazodalibep - Population 1 and 2

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    End point title
    		 Serum Concentrations of Dazodalibep - Population 1 and 2
    End point description
    Plasma concentrations of dazodalibep were reported. Analysis Population: The pharmacokinetic analysis set included all subjects who received IP and had at least one quantifiable serum PK observation post-first dose.
    End point type
    Secondary
    End point timeframe
    Day 1 predose, day 1 post-dose, day 15, day 29, day 57, day 85, day 113, day 141 predose, day 141 postdose, day 169 predose, day 169 postdose, day 197, day 225, day 253, day 281, day 309, day 365
    End point values
    		 Placebo - Dazodalibep 1500mg Population 1 - PK Set Dazodalibep 1500mg - Placebo Population 1 - PK Set Placebo - Dazodalibep 1500mg Population 2 - PK Set Dazodalibep 1500mg - Placebo Population 2 - PK Set
    Number of subjects analysed
    37 [25]
    36 [26]
    52 [27]
    54 [28]
    Units: Milliragm per liter
    arithmetic mean (standard deviation)
        Day 1, predose
    99999 ± 99999
    0.002 ± 0.013
    99999 ± 99999
    0.002 ± 0.013
        Day 1, Post dose
    99999 ± 99999
    470.370 ± 111.047
    99999 ± 99999
    496.984 ± 182.915
        Day 15
    99999 ± 99999
    97.058 ± 26.480
    99999 ± 99999
    111.636 ± 56.244
        Day 29
    99999 ± 99999
    128.228 ± 31.805
    99999 ± 99999
    141.365 ± 100.163
        Day 57
    99999 ± 99999
    62.363 ± 25.562
    99999 ± 99999
    80.093 ± 64.358
        Day 85
    99999 ± 99999
    53.716 ± 21.300
    99999 ± 99999
    68.812 ± 60.349
        Day 113
    99999 ± 99999
    25.796 ± 29.229
    99999 ± 99999
    66.778 ± 59.558
        Day 141, Predose
    99999 ± 99999
    49.318 ± 27.952
    99999 ± 99999
    80.912 ± 125.684
        Day 141, Postdose
    0.577 ± 99999
    525.702 ± 155.286
    25.004 ± 99999
    532.216 ± 241.670
        Day 169, predose
    99999 ± 99999
    50.390 ± 18.717
    99999 ± 99999
    54.031 ± 30.161
        Day 169, postdose
    469.366 ± 92.413
    65.459 ± 113.805
    572.071 ± 200.235
    57.018 ± 31.592
        Day 197
    39.535 ± 16.655
    10.808 ± 9.982
    39.399 ± 15.325
    14.958 ± 28.728
        Day 225
    46.885 ± 21.633
    1.903 ± 1.594
    73.173 ± 194.836
    1.979 ± 1.624
        Day 253
    45.069 ± 23.143
    0.360 ± 0.343
    63.950 ± 77.006
    0.427 ± 0.485
        Day 281
    46.368 ± 23.349
    0.086 ± 0.160
    54.050 ± 50.595
    0.139 ± 0.340
        Day 309
    52.409 ± 23.754
    0.008 ± 0.026
    44.732 ± 24.888
    0.018 ± 0.044
        Day 365
    2.446 ± 2.536
    0 ± 0
    1.531 ± 1.017
    0.003 ± 0.014
    Notes
    [25] - n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 36, 34, 37, 36, 36, 33, 21 99999 = Not applicable
    [26] - n = 36, 33, 35, 35, 34, 36, 31, 35, 33, 34, 34, 34, 32, 33, 33, 31, 22 99999 = Not applicable
    [27] - n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 51, 52, 51, 49, 49, 49, 46 99999 = Not Applicable
    [28] - n = 54, 52, 51, 52, 51, 51, 50, 48, 47, 51, 44, 48, 49, 49, 46, 46, 45 99999 = Not Applicable
    No statistical analyses for this end point

    Secondary: Number of Subjects With Positive Anti-Drug Antibodies (ADA) - Population 1 and 2

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    End point title
    		 Number of Subjects With Positive Anti-Drug Antibodies (ADA) - Population 1 and 2
    End point description
    Number of subjects with positive ADA were reported. Analysis population: Any VIB4920 analysis set.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug until end of the study (up to 365 days)
    End point values
    		 Placebo to Dazodalibep 1500mg - Population 1 - VIB4920 Set Dazodalibep 1500mg to Placebo - Population 1 - VIB4920 Set Placebo to Dazodalibep 1500 mg - Population 2 - VIB4920 Set Dazodalibep 1500mg to Placebo - Population 2 - VIB4920 Set
    Number of subjects analysed
    37
    36
    52
    54
    Units: Participants
    1
    6
    6
    12
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose until end of the study (up to 365 days)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Placebo Population 1 - Stage 1
    Reporting group description
    		 Subjects with moderate to severe systemic disease activity received placebo by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.

    Reporting group title
    Dazodalibep 1500 mg Population 1 -Stage 1
    Reporting group description
    		 Subjects with moderate to severe systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.

    Reporting group title
    Placebo to Dazodalibep 1500 mg Population 1 - Stage 2
    Reporting group description
    		 Subjects with moderate to severe systemic disease activity who received placebo had received dazodalibep 1500 mg by IV infusion, Q4W for five doses.

    Reporting group title
    Dazodalibep 1500 mg to Placebo Population 1 - Stage 2
    Reporting group description
    		 Subjects with moderate to severe systemic disease activity who received dazodalibep in stage 1 had received placebo, Q4W for five doses.

    Reporting group title
    Placebo Population 2 - Stage 1
    Reporting group description
    		 Subjects with low systemic disease activity received placebo by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.

    Reporting group title
    Dazodalibep 1500 mg - Population 2 - Stage 1
    Reporting group description
    		 Subjects with low systemic disease activity received dazodalibep 1500 mg by IV infusion, Q2W for three doses and then Q4W for 4 additional doses.

    Reporting group title
    Placebo to Dazodalibep 1500 mg Population 2 - Stage 2
    Reporting group description
    		 Subjects with low systemic disease activity who received placebo in stage 1 had received dazodalibep 1500 mg by IV infusion, Q4W for five doses in stage 2.

    Reporting group title
    Dazodalibep 1500 mg to Placebo Population 2 - Stage 2
    Reporting group description
    		 Subjects with low systemic disease activity who received dazodalibep in stage 1 had received placebo by IV infusion, Q4W for five doses in stage 2.

    Serious adverse events
    		 Placebo Population 1 - Stage 1 Dazodalibep 1500 mg Population 1 -Stage 1 Placebo to Dazodalibep 1500 mg Population 1 - Stage 2 Dazodalibep 1500 mg to Placebo Population 1 - Stage 2 Placebo Population 2 - Stage 1 Dazodalibep 1500 mg - Population 2 - Stage 1 Placebo to Dazodalibep 1500 mg Population 2 - Stage 2 Dazodalibep 1500 mg to Placebo Population 2 - Stage 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 36 (2.78%)
    1 / 37 (2.70%)
    3 / 34 (8.82%)
    1 / 55 (1.82%)
    3 / 54 (5.56%)
    1 / 52 (1.92%)
    2 / 49 (4.08%)
         number of deaths (all causes)
    0
    1
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    1
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Gammopathy
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    1 / 54 (1.85%)
    0 / 52 (0.00%)
    0 / 49 (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
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    1 / 49 (2.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Multiple injuries
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    1 / 34 (2.94%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (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
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    1 / 34 (2.94%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (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
    Cardiac disorders
    Atrial flutter
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    1 / 52 (1.92%)
    0 / 49 (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
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 36 (2.78%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    1 / 55 (1.82%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (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
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    1 / 34 (2.94%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (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
    Hepatobiliary disorders
    Cholecystitis chronic
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    1 / 37 (2.70%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (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
    Drug-induced liver injury
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 36 (2.78%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 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
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 36 (2.78%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (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
    Pneumonia influenzal
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    1 / 54 (1.85%)
    0 / 52 (0.00%)
    0 / 49 (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
    Post-acute COVID-19 syndrome
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    1 / 54 (1.85%)
    0 / 52 (0.00%)
    0 / 49 (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
    Urinary tract infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    1 / 49 (2.04%)
         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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Population 1 - Stage 1 Dazodalibep 1500 mg Population 1 -Stage 1 Placebo to Dazodalibep 1500 mg Population 1 - Stage 2 Dazodalibep 1500 mg to Placebo Population 1 - Stage 2 Placebo Population 2 - Stage 1 Dazodalibep 1500 mg - Population 2 - Stage 1 Placebo to Dazodalibep 1500 mg Population 2 - Stage 2 Dazodalibep 1500 mg to Placebo Population 2 - Stage 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 38 (26.32%)
    11 / 36 (30.56%)
    17 / 37 (45.95%)
    18 / 34 (52.94%)
    13 / 55 (23.64%)
    15 / 54 (27.78%)
    9 / 52 (17.31%)
    10 / 49 (20.41%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 38 (2.63%)
    3 / 36 (8.33%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    1
    5
    0
    0
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    5 / 38 (13.16%)
    4 / 36 (11.11%)
    4 / 37 (10.81%)
    2 / 34 (5.88%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    8
    5
    6
    2
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    2 / 55 (3.64%)
    4 / 54 (7.41%)
    0 / 52 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    4
    0
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    3 / 38 (7.89%)
    2 / 36 (5.56%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    4
    2
    0
    0
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    2 / 37 (5.41%)
    3 / 34 (8.82%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    0
    2
    3
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    3 / 37 (8.11%)
    2 / 34 (5.88%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    0
    4
    2
    0
    0
    0
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 38 (0.00%)
    4 / 36 (11.11%)
    6 / 37 (16.22%)
    6 / 34 (17.65%)
    7 / 55 (12.73%)
    8 / 54 (14.81%)
    9 / 52 (17.31%)
    5 / 49 (10.20%)
         occurrences all number
    0
    4
    6
    6
    7
    8
    10
    5
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 38 (5.26%)
    3 / 36 (8.33%)
    5 / 37 (13.51%)
    5 / 34 (14.71%)
    4 / 55 (7.27%)
    2 / 54 (3.70%)
    0 / 52 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    3
    3
    6
    7
    5
    2
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    2 / 37 (5.41%)
    2 / 34 (5.88%)
    0 / 55 (0.00%)
    0 / 54 (0.00%)
    0 / 52 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    0
    0
    4
    3
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 36 (0.00%)
    0 / 37 (0.00%)
    0 / 34 (0.00%)
    5 / 55 (9.09%)
    5 / 54 (9.26%)
    2 / 52 (3.85%)
    6 / 49 (12.24%)
         occurrences all number
    0
    0
    0
    0
    5
    5
    2
    6

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Jul 2020
    Text addressing COVID-19 risk, and steps to minimize COVID-19 risk was added. This includes the requirement for a negative SARS-CoV-2 test within 2 weeks prior to randomization. SARS-CoV-2 testing added to screening procedures. Text providing additional details regarding appropriate contraception methods that must be adhered to in order to meet eligibility criteria was added. The phrase “(the minimum age for adult participants can be higher than 18 years in countries with different regulations)” was added. Text clarifying additional exclusion criteria relating to infections (bacterial/viral/other), including COVID-19 risk was added. The screening procedure “Exploratory biomarker sample (serum)” added. Number of visits when an autoantibody panel needs to be conducted has been revised. The term “cryoglobulins” was deleted from “C3, C4, serum free light chains, cryoglobulins, serum and urine immunofixation” procedure. Exploratory Flow Cytometry (T-reg panel)” procedure deleted from schedule of study assessments. Inserted requirement for additional urine pregnancy test(s) at Visit 15 and EDV. The procedures “Autoantibody panel” and “Cryoglobulins” deleted. IgE was removed from the list of plasma immunoglobulins to be assessed. Assessment of T regulatory cells removed from exploratory flow cytometry. Text inserted explaining Investigator discretion to give “medications that are considered necessary for the safety and well-being of subjects”. New section stating, “The initiation or increase in dose of the restricted medications in Section 7.4.2 are also considered as rescue medications for Population #1” was inserted. New section stating, “The initiation or increase in dose of the restricted medications in Section7.4.4 are also considered as rescue medications for Population #2” was inserted.
    07 Oct 2022
    Text clarifying the MR team will remain blinded to the treatment assignment for individual subjects until the completion of the study. Text clarifying any communication of unblinded results will be documented in an unblinding memo. Population-based treatment group level results may be released after completion of primary analysis.

    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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