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    Clinical Trial Results:
    A Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-ranging, Phase 2b Study to Evaluate Efficacy and Safety of Tezepelumab for the Treatment of Chronic Spontaneous Urticaria

    Summary
    EudraCT number
    		 2020-002759-39
    Trial protocol
    		 GR   FR   IT   ES   PL  
    Global end of trial date
    13 Apr 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Apr 2024
    First version publication date
    12 Apr 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    20190194
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04833855
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States,
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.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
    13 Apr 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Apr 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the study was to evaluate the effect of tezepelumab on improvement in the Urticaria Activity Score over 7 days (UAS7).
    Protection of trial subjects
    The study was conducted in accordance with the protocol and with consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Conference on Harmonisation (ICH) Good Clinical Practice Guidelines, and applicable ICH laws and regulations.
    Background therapy
    		 Participants maintained a stable dose of second generation H1-antihistamines (sgAH) as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Apr 2021
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 4 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Japan: 38
    Country: Number of subjects enrolled
    Korea, Republic of: 16
    Country: Number of subjects enrolled
    France: 5
    Country: Number of subjects enrolled
    Germany: 10
    Country: Number of subjects enrolled
    Greece: 13
    Country: Number of subjects enrolled
    Italy: 9
    Country: Number of subjects enrolled
    Poland: 16
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    United States: 38
    Country: Number of subjects enrolled
    Canada: 26
    Worldwide total number of subjects
    183
    EEA total number of subjects
    65
    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)
    168
    From 65 to 84 years
    15
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were enrolled at 56 study centers in Japan, Republic of Korea, France, Germany, Greece, Italy, Poland, Spain, Canada, and the United States, and participated from 15 April 2021 to 13 April 2023.

    Pre-assignment
    Screening details
    		 Participants with chronic spontaneous urticaria (CSU) and symptomatic despite treatment with sgAH were randomized based on if they were previously treated with anti-immunoglobulin E (IgE) therapies or were anti-IgE naïve.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive placebo subcutaneously (SC) every 2 weeks (Q2W) for 16 weeks. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received placebo SC Q2W for 16 weeks.

    Arm title
    		 Omalizumab 300 mg SC Q4W
    Arm description
    		 Participants without previous anti-IgE experience were randomized to receive omalizumab 300 mg SC every 4 weeks (Q4W) for 16 weeks. Participants received placebo SC at intervening study visits to ensure all participants received an injection Q2W. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received placebo SC Q4W at intervening study visits for 16 weeks, to ensure participants received an injection Q2W.

    Investigational medicinal product name
    Omalizumab
    Investigational medicinal product code
    Other name
    Xolair®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received omalizumab 300 mg SC Q4W for 16 weeks. Participants received placebo SC at intervening study visits to ensure all participants received an injection Q2W.

    Arm title
    		 Tezepelumab 210 mg SC Q4W
    Arm description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive tezepelumab 210 mg SC Q4W for 16 weeks. Participants received placebo SC at intervening study visits to ensure all participants received an injection Q2W. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received placebo SC Q4W at intervening study visits for 16 weeks, to ensure participants received an injection Q2W.

    Investigational medicinal product name
    Tezepelumab
    Investigational medicinal product code
    AMG 157
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received tezepelumab 210 mg SC Q4W for 16 weeks. Participants received placebo SC at intervening study visits to ensure all participants received an injection Q2W.

    Arm title
    		 Tezepelumab 420 mg SC Q2W
    Arm description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive tezepelumab 420 mg SC Q2W for 16 weeks. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tezepelumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received tezepelumab 420 mg SC Q4W for 16 weeks.

    Number of subjects in period 1
    		Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Started
    48
    31
    52
    52
    Completed
    43
    29
    45
    48
    Not completed
    5
    2
    7
    4
         Consent withdrawn by subject
    4
    1
    3
    1
         Protocol specified criteria
    -
    -
    2
    1
         Lost to follow-up
    1
    -
    2
    2
         Decision by sponsor
    -
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive placebo subcutaneously (SC) every 2 weeks (Q2W) for 16 weeks. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Reporting group title
    Omalizumab 300 mg SC Q4W
    Reporting group description
    		 Participants without previous anti-IgE experience were randomized to receive omalizumab 300 mg SC every 4 weeks (Q4W) for 16 weeks. Participants received placebo SC at intervening study visits to ensure all participants received an injection Q2W. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Reporting group title
    Tezepelumab 210 mg SC Q4W
    Reporting group description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive tezepelumab 210 mg SC Q4W for 16 weeks. Participants received placebo SC at intervening study visits to ensure all participants received an injection Q2W. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Reporting group title
    Tezepelumab 420 mg SC Q2W
    Reporting group description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive tezepelumab 420 mg SC Q2W for 16 weeks. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Reporting group values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W Total
    Number of subjects
    		 48 31 52 52 183
    Age Categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 44 30 47 47 168
        From 65-84 years
    		 4 1 5 5 15
        85 years and over
    		 0 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 42.8 ( 15.2 ) 39.8 ( 13.1 ) 45.0 ( 14.7 ) 42.9 ( 14.5 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 37 23 35 39 134
        Male
    		 11 8 17 13 49
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 3 2 3 6 14
        Not Hispanic or Latino
    		 45 29 49 46 169
        Unknown or Not Reported
    		 0 0 0 0 0
    Race, Customized
    Units: Subjects
        Asian
    		 18 12 16 14 60
        Black or African American
    		 1 2 2 2 7
        Multiple
    		 0 0 0 1 1
        White
    		 29 17 34 34 114
        Other
    		 0 0 0 1 1

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive placebo subcutaneously (SC) every 2 weeks (Q2W) for 16 weeks. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Reporting group title
    Omalizumab 300 mg SC Q4W
    Reporting group description
    		 Participants without previous anti-IgE experience were randomized to receive omalizumab 300 mg SC every 4 weeks (Q4W) for 16 weeks. Participants received placebo SC at intervening study visits to ensure all participants received an injection Q2W. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Reporting group title
    Tezepelumab 210 mg SC Q4W
    Reporting group description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive tezepelumab 210 mg SC Q4W for 16 weeks. Participants received placebo SC at intervening study visits to ensure all participants received an injection Q2W. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Reporting group title
    Tezepelumab 420 mg SC Q2W
    Reporting group description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive tezepelumab 420 mg SC Q2W for 16 weeks. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Primary: Change from Baseline in UAS7 at Week 16

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    End point title
    		 Change from Baseline in UAS7 at Week 16
    End point description
    The UAS is a CSU-specific patient-reported outcome measure with 2 components: Hives Severity Score (HSS) for number of wheals and an Itch Severity Score (ISS) for itch intensity, and are each scored from 0 (no wheals, no itch) to 3 (>50 wheals, severe itch) for the previous 24 hours. The HSS and ISS are combined to give a daily UAS ranging from 0 to 6. The sum of the daily UAS over a 7-day period provides the UAS7, from 0 (no symptoms) to 42 (severe urticaria). The least squares mean (LSM) estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline UAS7, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in urticaria activity. The full analysis set (FAS) included all randomized participants who received at least 1 dose of investigational product.
    End point type
    Primary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    48
    31
    52
    52
    Units: score on a scale
        least squares mean (standard error)
    -13.6 ( 1.6 )
    -18.4 ( 2.0 )
    -13.5 ( 1.6 )
    -14.7 ( 1.5 )
    Statistical analysis title
    		 Tezepelumab 420 mg SC Q2W - Placebo
    Comparison groups
    Placebo v Tezepelumab 420 mg SC Q2W
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6 [1]
    Method
    		 Repeated measure model
    Parameter type
    		 LSM difference
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 3.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.2
    Notes
    [1] - Nominal p-value. Model parameters: stratification factor (prior anti-IgE status), baseline UAS7, treatment, study week, interaction between treatment and study week.
    Statistical analysis title
    		 Tezepelumab 210 mg SC Q4W - Placebo
    Comparison groups
    Placebo v Tezepelumab 210 mg SC Q4W
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.99 [2]
    Method
    		 Repeated measure model
    Parameter type
    		 LSM difference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.3
         upper limit
    		 4.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.2
    Notes
    [2] - Nominal p-value. Model parameters: stratification factor (prior anti-IgE status), baseline UAS7, treatment, study week, interaction between treatment and study week.

    Secondary: Change from Baseline in ISS over 7 Days (ISS7) at Week 16

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    End point title
    		 Change from Baseline in ISS over 7 Days (ISS7) at Week 16
    End point description
    The ISS is a component of the UAS, a CSU-specific patient-reported outcome measure and assessed itch intensity, with daily scores ranging from 0 (no itch) to 3 (severe itch) for the previous 24 hours. The sum of daily ISS over a 7-day period provides the ISS7, from 0 (no symptoms) to 21 (severe itch). The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline ISS7, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in urticaria activity. The FAS included all randomized participants who received at least 1 dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    48
    31
    52
    52
    Units: score on a scale
        least squares mean (standard error)
    -7.7 ( 0.8 )
    -9.6 ( 1.0 )
    -7.3 ( 0.8 )
    -8.0 ( 0.8 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in HSS over 7 Days (HSS7) at Week 16

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    End point title
    		 Change from Baseline in HSS over 7 Days (HSS7) at Week 16
    End point description
    The HSS is a component of the UAS, a CSU-specific patient-reported outcome measure and assessed the number of wheals, with daily scores ranging from 0 (no wheals) to 3 (>50 wheals) for the previous 24 hours. The sum of daily HSS over a 7-day period provides the HSS7, from 0 (no symptoms) to 21 (severe wheals). The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline HSS7, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in urticaria activity. The FAS included all randomized participants who received at least 1 dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    48
    31
    52
    52
    Units: score on a scale
        least squares mean (standard error)
    -5.8 ( 0.8 )
    -8.8 ( 1.1 )
    -6.3 ( 0.8 )
    -6.7 ( 0.8 )
    No statistical analyses for this end point

    Secondary: Number of Participants with a UAS7 of ≤ 6 (Minimal Residual Disease) at Week 16

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    End point title
    		 Number of Participants with a UAS7 of ≤ 6 (Minimal Residual Disease) at Week 16
    End point description
    The sum of the daily UAS over a 7-day period provides the UAS7, from 0 (no symptoms) to 42 (severe urticaria). Minimal residual disease in UAS7 was defined as a score ≤ 6 and indicates well-controlled urticaria and a good response to treatment. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    39
    25
    39
    48
    Units: participants
    8
    14
    10
    13
    No statistical analyses for this end point

    Secondary: Number of Participants with a Change from Baseline in UAS7 of ≤ -10 (Minimal Important Difference)

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    End point title
    		 Number of Participants with a Change from Baseline in UAS7 of ≤ -10 (Minimal Important Difference)
    End point description
    The sum of the daily UAS over a 7-day period provides the UAS7, from 0 (no symptoms) to 42 (severe urticaria). Minimal important difference in UAS7 was defined as a change from baseline of ≤ -10. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    39
    25
    39
    48
    Units: participants
    28
    20
    27
    32
    No statistical analyses for this end point

    Secondary: Number of Participants with ISS7 = 0 at Week 16 (Complete Resolution)

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    End point title
    		 Number of Participants with ISS7 = 0 at Week 16 (Complete Resolution)
    End point description
    The sum of daily ISS over a 7-day period provides the ISS7, from 0 (no symptoms) to 21 (severe itch). An ISS7 = 0 indicates a complete resolution of itch. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    39
    25
    39
    48
    Units: participants
    4
    12
    7
    9
    No statistical analyses for this end point

    Secondary: Number of Participants with a UAS7 = 0 at Week 16 (Complete Response)

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    End point title
    		 Number of Participants with a UAS7 = 0 at Week 16 (Complete Response)
    End point description
    The sum of the daily UAS over a 7-day period provides the UAS7, from 0 (no symptoms) to 42 (severe urticaria). A complete response was defined as UAS7 = 0 at Week 16. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    39
    25
    39
    48
    Units: participants
    4
    11
    7
    5
    No statistical analyses for this end point

    Secondary: Number of Participants with HSS7 = 0 at Week 16 (Complete Resolution)

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    End point title
    		 Number of Participants with HSS7 = 0 at Week 16 (Complete Resolution)
    End point description
    The sum of daily HSS over a 7-day period provides the HSS7, from 0 (no symptoms) to 21 (severe wheals). An HSS7 = 0 indicates a complete resolution of hives. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    39
    25
    39
    48
    Units: participants
    6
    11
    8
    6
    No statistical analyses for this end point

    Secondary: Number of Participants with a Change from Baseline in ISS7 of ≤ -5 (Minimal Important Difference)

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    End point title
    		 Number of Participants with a Change from Baseline in ISS7 of ≤ -5 (Minimal Important Difference)
    End point description
    The sum of daily ISS over a 7-day period provides the ISS7, from 0 (no symptoms) to 21 (severe itch). Minimal important difference in ISS7 was defined as a change from baseline of ≤ -5. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    39
    25
    39
    48
    Units: participants
    29
    20
    28
    34
    No statistical analyses for this end point

    Secondary: Number of Participants with a Change from Baseline in HSS7 of ≤ -5.5 (Minimal Important Difference)

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    End point title
    		 Number of Participants with a Change from Baseline in HSS7 of ≤ -5.5 (Minimal Important Difference)
    End point description
    The sum of daily HSS over a 7-day period provides the HSS7, from 0 (no symptoms) to 21 (severe wheals). Minimal important difference in HSS7 was defined as a change from baseline of ≤ -5.5. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    39
    25
    39
    48
    Units: participants
    23
    19
    24
    31
    No statistical analyses for this end point

    Secondary: Change from Baseline in Weekly Sleep Quality Score (SQS7): Sum of Daily SQS at Week 16

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    End point title
    		 Change from Baseline in Weekly Sleep Quality Score (SQS7): Sum of Daily SQS at Week 16
    End point description
    The SQS was assessed by the participant through 3 questions relating to falling asleep (Q1), wakefulness (Q2), and feeling rested in the morning (Q3). The sum of the 3 daily sleep quality items over 7 days, ranged from 0 (good quality sleep) to 63 (poor quality sleep). The LSM estimates were based on the repeated measure model with stratification factor (prior anti-IgE status), baseline SQS7 - sum of SQS, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in sleep quality. The FAS included all randomized participants who received at least 1 dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    48
    31
    52
    52
    Units: score on a scale
        least squares mean (standard error)
    -19.5 ( 1.8 )
    -16.7 ( 2.3 )
    -18.3 ( 1.7 )
    -17.1 ( 1.6 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Weekly Sleep Interference Score (SIS7) at Week 16

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    End point title
    		 Change from Baseline in Weekly Sleep Interference Score (SIS7) at Week 16
    End point description
    The SIS is part of the Urticaria Patient Daily Diary and was assessed by the participant using the electronic diary once daily in the morning. Participants scored sleep interference on a scale of 0 (no interference) to 3 (substantial, woke up often, severe interference with sleep). The SIS7 was a sum of the daily scores over 7 days. The LSM estimates were based on the repeated measure model with stratification factor (prior anti-IgE status), baseline SIS7, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in sleep interference. The FAS included all randomized participants who received at least 1 dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    48
    31
    52
    52
    Units: score on a scale
        least squares mean (standard error)
    -8.4 ( 0.7 )
    -6.5 ( 0.9 )
    -7.4 ( 0.7 )
    -7.8 ( 0.7 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in SQS7: Sum of Average Daily Q1 - Q3 at Week 16

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    End point title
    		 Change from Baseline in SQS7: Sum of Average Daily Q1 - Q3 at Week 16
    End point description
    The SQS was assessed by the participant through 3 questions relating to falling asleep (Q1), wakefulness (Q2), and feeling rested in the morning (Q3). The sum of average daily Q1 - Q3 score was generated by averaging 3 daily sleep quality items and then summing the daily average over 7 days with a score ranging from 0 (good quality sleep) to 21 (poor quality sleep) (sum of the average daily Q1 - Q3). The LSM estimates were based on the repeated measure model with stratification factor (prior anti-IgE status), baseline SQS7 - sum of average daily Q1 - Q3, treatment, study week and the interaction between treatment and study week. A negative change from baseline indicates an improvement in sleep quality.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    48
    31
    52
    52
    Units: score on a scale
        least squares mean (standard error)
    -6.5 ( 0.6 )
    -5.6 ( 0.8 )
    -6.1 ( 0.6 )
    -5.7 ( 0.5 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Urticaria Control Test (UCT) Score at Week 16

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    End point title
    		 Change from Baseline in Urticaria Control Test (UCT) Score at Week 16
    End point description
    The UCT assesses disease control in participants with CSU through a retrospective validated scoring system, evaluating the physical symptoms of chronic urticaria (itch, hives and/or angioedema) and the effectiveness of treatment over 4 weeks. It consists of 4 questions with 5 answer options, scored from 0 to 4, and the UCT score is the sum of all 4 questions, with total score ranging from 0 (no control) to 16 (complete control). A score of ≥ 12 indicates well-controlled urticaria and a score of ≤ 11 points indicates poor disease control. A positive change from baseline indicates an improvement in disease control. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline UCT score, treatment, study week and the interaction between treatment and study week. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    46
    29
    48
    49
    Units: score on a scale
        least squares mean (standard error)
    4.1 ( 0.6 )
    6.3 ( 0.8 )
    4.9 ( 0.6 )
    5.9 ( 0.6 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Weekly Angioedema Activity Score (AAS7) at Week 16

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    End point title
    		 Change from Baseline in Weekly Angioedema Activity Score (AAS7) at Week 16
    End point description
    The AAS is a 5-item patient-reported outcome measure used to determine angioedema activity. Participants retrospectively documented the presence or absence of angioedema in the past 24 hours, and the AAS daily score ranged from 0 to 15 points, assessing 5 key factors when angioedema is present, including duration, physical discomfort, impact on daily activities, impact on appearance, and overall severity). The daily AAS scores are summed for 7 days to form the AAS7 with a range of 0 (not present) to 105 (most severe angioedema activity). Negative changes from baseline indicate an improvement in angioedema activity. The LSM estimates were based on the repeated measure model with stratification factor (prior anti-IgE status), baseline AAS7, treatment, study week and the interaction between treatment and study week. The FAS included all randomized participants who received at least 1 dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    48
    31
    52
    52
    Units: score on a scale
        least squares mean (standard error)
    -19.0 ( 2.7 )
    -18.7 ( 3.5 )
    -20.8 ( 2.7 )
    -15.6 ( 2.5 )
    No statistical analyses for this end point

    Secondary: Number of Cumulative Weeks that Participants Achieved AAS7 = 0 at Week 16 (Angioedema Occurrence Free)

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    End point title
    		 Number of Cumulative Weeks that Participants Achieved AAS7 = 0 at Week 16 (Angioedema Occurrence Free)
    End point description
    The AAS is a 5-item patient-reported outcome measure used to determine angioedema activity. Participants retrospectively documented the presence or absence of angioedema in the past 24 hours, and the AAS daily score ranged from 0 to 15 points, assessing 5 key factors when angioedema is present, including duration, physical discomfort, impact on daily activities, impact on appearance, and overall severity). The daily AAS scores are summed for 7 days to form the AAS7 with a range of 0 (not present) to 105 (most severe angioedema activity). Angioedema occurrence free was defined as AAS7 = 0. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    40
    26
    44
    37
    Units: weeks
        arithmetic mean (standard deviation)
    10.8 ( 5.2 )
    11.3 ( 4.9 )
    9.9 ( 5.8 )
    11.5 ( 5.4 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Week 16

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    End point title
    		 Change from Baseline in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Week 16
    End point description
    The CU-Q2oL is a 23-item, self-reported urticaria-specific measure to evaluate 6 dimensions of quality of life (QoL): pruritus, impact on life activities, sleep problems, limitations, looks, and swelling. The total score is transformed to a linear scale of 0 to 100 with a higher CU-Q2oL score indicating a higher QoL impairment. A negative change from baseline indicates an improvement in QoL. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline CU-Q2oL score, treatment, study week and the interaction between treatment and study week. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    44
    25
    41
    44
    Units: score on a scale
        least squares mean (standard error)
    -19.6 ( 2.1 )
    -19.8 ( 2.8 )
    -19.3 ( 2.2 )
    -18.7 ( 2.1 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Dermatology Life Quality Index (DLQI) at Week 16

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    End point title
    		 Change from Baseline in the Dermatology Life Quality Index (DLQI) at Week 16
    End point description
    The DLQI is a 10-item, participant-completed, health-related QoL assessment with content specific to those with dermatology conditions. The DLQI evaluates participant perceptions including dermatology-related symptoms and feelings, impacts on daily activities, leisure, work or school, personal relationships, and side effects of treatment. The recall period was 1 week. The DLQI total score ranges from 0 to 30 with a higher score indicating a greater QoL impairment. A negative change from baseline indicates an improvement in QoL. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline DLQI score, treatment, study week and the interaction between treatment and study week. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data are included.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    44
    25
    41
    44
    Units: score on a scale
        least squares mean (standard error)
    -7.4 ( 0.9 )
    -7.3 ( 1.2 )
    -7.0 ( 0.9 )
    -7.0 ( 0.9 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Angioedema Quality of Life Questionnaire (AE-QoL) at Week 16

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    End point title
    		 Change from Baseline in the Angioedema Quality of Life Questionnaire (AE-QoL) at Week 16
    End point description
    The AE-QoL is a validated angioedema QoL questionnaire for participants with angioedema. It consists of 17 questions evaluating 4 domains including functioning, fatigue/mood, fear/shame, and food with a recall period of 4 weeks. The total score is transformed to a linear scale ranging from 0 to 100, with a higher score indicating a worse impairment in QoL. A negative change from baseline indicates an improvement in QoL. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline AE-QoL score, treatment, study week and the interaction between treatment and study week. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with angioedema presence at baseline and at least 1 non-missing AE-QoL record were included.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    20
    7
    15
    16
    Units: score on a scale
        least squares mean (standard error)
    -29.2 ( 6.0 )
    -24.1 ( 10.9 )
    -24.6 ( 6.4 )
    -13.1 ( 7.4 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Angioedema Control Test (AECT) Score at Week 16

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    End point title
    		 Change from Baseline in the Angioedema Control Test (AECT) Score at Week 16
    End point description
    The AECT is a patient-reported outcome measure to evaluate disease control in the domains of signs and symptoms, QoL, anxiety/fear, and effectiveness of therapy. The total AECT score ranges from 0 to 16, with higher scores indicating better controlled disease. A positive change from baseline indicates an improvement in angioedema control. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline AECT score, treatment, study week and the interaction between treatment and study week. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with angioedema presence at baseline and at least 1 non-missing AECT record were included.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    20
    7
    15
    16
    Units: score on a scale
        least squares mean (standard error)
    4.2 ( 1.2 )
    3.9 ( 2.2 )
    4.6 ( 1.3 )
    2.3 ( 1.5 )
    No statistical analyses for this end point

    Secondary: Number of Participants with an AECT Score = 16 at Week 16 (Complete Control)

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    End point title
    		 Number of Participants with an AECT Score = 16 at Week 16 (Complete Control)
    End point description
    The total AECT score ranges from 0 to 16, with higher scores indicating better controlled disease. Complete control was defined as AECT score = 16. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data at Week 16 and angioedema presence at baseline and at least 1 non-missing AECT record were included.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    15
    5
    14
    14
    Units: participants
    3
    2
    0
    1
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Work Productivity and Activity Impairment Questionnaire: Chronic Urticaria (WPAI-CU) Score at Week 16

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    End point title
    		 Change from Baseline in the Work Productivity and Activity Impairment Questionnaire: Chronic Urticaria (WPAI-CU) Score at Week 16
    End point description
    The WPAI-CU is a questionnaire that assesses the impact of an intervention on work productivity, evaluating 4 areas including absenteeism, presenteeism, work productivity loss, and activity impairment over the past 7 days. Each of the areas is scored separately as a percentage, with higher numbers indicating greater impairment and less productivity. A negative change from baseline indicates an improvement. The LSM estimates are based on the repeated measure model with stratification factor (prior anti-IgE status), baseline WPAI-CU score, treatment, study week and the interaction between treatment and study week. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with observed data were included for each question.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    44
    25
    41
    44
    Units: score on a scale
    least squares mean (standard error)
        Absenteeism (n=33, 20, 28, 26)
    -4.7 ( 2.5 )
    0.3 ( 3.0 )
    -7.5 ( 2.5 )
    -2.3 ( 2.7 )
        Presenteeism (n=32, 19, 27, 24)
    -19.9 ( 5.2 )
    -18.3 ( 6.6 )
    -20.3 ( 5.3 )
    -17.8 ( 5.7 )
        Work productivity loss (n=32, 19, 27, 24)
    -20.0 ( 5.4 )
    -13.3 ( 6.7 )
    -23.5 ( 5.5 )
    -17.5 ( 5.9 )
        Activity impairment (n=44, 25, 41, 44)
    -28.5 ( 4.2 )
    -30.3 ( 5.6 )
    -27.2 ( 4.3 )
    -24.1 ( 4.1 )
    No statistical analyses for this end point

    Secondary: Number of Cumulative Days of sgAH Rescue Medication Use from Baseline to Week 16

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    End point title
    		 Number of Cumulative Days of sgAH Rescue Medication Use from Baseline to Week 16
    End point description
    Participants recorded any need of sgAH rescue medication in their daily electronic diary. The FAS included all randomized participants who received at least 1 dose of investigational product. Participants with data available are included.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 16
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    22
    19
    31
    25
    Units: days
        least squares mean (standard deviation)
    49.5 ( 39.0 )
    31.6 ( 42.7 )
    46.1 ( 39.3 )
    32.7 ( 33.4 )
    No statistical analyses for this end point

    Secondary: Serum Concentration of Tezepelumab

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    End point title
    		 Serum Concentration of Tezepelumab [3]
    End point description
    The lower limit of quantification was 10 ng/mL, and values below this limit were set to zero. The pharmacokinetic analysis set included participants who received tezepelumab and had at least 1 sample with a measurable serum concentration. Participants with data available at each time point are included.
    End point type
    Secondary
    End point timeframe
    Week 1 pre-dose, Weeks 2, 4, 8, 12, 16, 24, and 32
    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: The pre-specified endpoint is for the serum concentration of tezepelumab in the tezepelumab 210 mg SC Q4W and tezepelumab 420 mg SC Q2W treatment arms only.
    End point values
    		 Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    51
    52
    Units: µg/mL
    arithmetic mean (standard deviation)
        Week 1 (n=51, 52)
    0.00 ( 0.00 )
    0.00 ( 0.00 )
        Week 2 (n=51, 48)
    20.1 ( 6.93 )
    41.3 ( 12.4 )
        Week 4 (n=46, 47)
    14.2 ( 5.78 )
    71.3 ( 20.8 )
        Week 8 (n=41, 43)
    21.2 ( 8.54 )
    101 ( 30.5 )
        Week 12 (n=38, 43)
    24.8 ( 9.67 )
    123 ( 44.1 )
        Week 16 (n= 39, 41)
    27.1 ( 10.7 )
    136 ( 43.4 )
        Week 24 (n=37, 39)
    6.95 ( 5.65 )
    37.3 ( 21.1 )
        Week 32 (n=40, 42)
    1.73 ( 1.73 )
    11.0 ( 10.8 )
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment-emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Participants with Treatment-emergent Adverse Events (TEAEs)
    End point description
    An adverse event (AE) was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with study treatment. TEAEs were AEs that started on or after the first dose of investigational product up to the end of study (Week 32). A serious AE (SAE) was defined as any untoward medical occurrence that met at least 1 of the following serious criteria: immediately life-threatening, required hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other medically important serious event. The safety analysis set consisted of all randomized participants who received at least 1 dose of investigational product.
    End point type
    Secondary
    End point timeframe
    Day 1 Week 1 to Week 32
    End point values
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Number of subjects analysed
    48
    31
    52
    52
    Units: participants
        TEAEs
    23
    24
    29
    28
        SAEs
    0
    1
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Deaths collected from enrollment to the end of study visit, up to 38 weeks. SAEs and other AEs were collected from Day 1 up to Week 32, up to 32 weeks.
    Adverse event reporting additional description
    Final Analysis
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive placebo SC Q2W for 16 weeks. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Reporting group title
    Omalizumab 300 mg SC Q4W
    Reporting group description
    		 Participants without previous anti-IgE experience were randomized to receive omalizumab 300 mg SC Q4W for 16 weeks. Participants received placebo SC at intervening study visits to ensure all participants received an injection Q2W. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Reporting group title
    Tezepelumab 210 mg SC Q4W
    Reporting group description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive tezepelumab 210 mg SC Q4W for 16 weeks. Participants received placebo SC at intervening study visits to ensure all participants received an injection Q2W. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Reporting group title
    Tezepelumab 420 mg SC Q2W
    Reporting group description
    		 Participants with and without previous anti-IgE therapy experience were randomized to receive tezepelumab 420 mg SC Q2W for 16 weeks. Participants maintained a stable dose of sgAH as background medication from screening Visit 2 (Day -14) to the end of the Safety Follow-up Period (up to Week 32).

    Serious adverse events
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 31 (3.23%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia
         subjects affected / exposed
    0 / 48 (0.00%)
    0 / 31 (0.00%)
    1 / 52 (1.92%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Intentional self-injury
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 31 (3.23%)
    0 / 52 (0.00%)
    0 / 52 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Omalizumab 300 mg SC Q4W Tezepelumab 210 mg SC Q4W Tezepelumab 420 mg SC Q2W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 48 (29.17%)
    7 / 31 (22.58%)
    19 / 52 (36.54%)
    20 / 52 (38.46%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 48 (4.17%)
    1 / 31 (3.23%)
    5 / 52 (9.62%)
    6 / 52 (11.54%)
         occurrences all number
    3
    1
    15
    8
    General disorders and administration site conditions
    Injection site pain
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 31 (0.00%)
    4 / 52 (7.69%)
    1 / 52 (1.92%)
         occurrences all number
    8
    0
    9
    1
    Pyrexia
         subjects affected / exposed
    1 / 48 (2.08%)
    3 / 31 (9.68%)
    3 / 52 (5.77%)
    2 / 52 (3.85%)
         occurrences all number
    1
    3
    10
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 48 (0.00%)
    0 / 31 (0.00%)
    2 / 52 (3.85%)
    3 / 52 (5.77%)
         occurrences all number
    0
    0
    2
    3
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    3 / 48 (6.25%)
    1 / 31 (3.23%)
    2 / 52 (3.85%)
    0 / 52 (0.00%)
         occurrences all number
    3
    1
    3
    0
    Urticaria
         subjects affected / exposed
    4 / 48 (8.33%)
    0 / 31 (0.00%)
    4 / 52 (7.69%)
    3 / 52 (5.77%)
         occurrences all number
    5
    0
    5
    4
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 48 (0.00%)
    0 / 31 (0.00%)
    1 / 52 (1.92%)
    3 / 52 (5.77%)
         occurrences all number
    0
    0
    1
    3
    Infections and infestations
    COVID-19
         subjects affected / exposed
    3 / 48 (6.25%)
    2 / 31 (6.45%)
    8 / 52 (15.38%)
    5 / 52 (9.62%)
         occurrences all number
    3
    2
    8
    5
    Nasopharyngitis
         subjects affected / exposed
    2 / 48 (4.17%)
    1 / 31 (3.23%)
    1 / 52 (1.92%)
    3 / 52 (5.77%)
         occurrences all number
    4
    1
    1
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Sep 2021
    - To incorporate regulatory authority recommendations, to align with international treatment guidelines, to reduce patient burden, and improve study experience by reducing the frequency of select eDiary data collection. - Updated schedule of activities to reduce frequency of chronic urticaria QoL questionnaire, DLQI assessment, work productivity, and activity impairment questionnaire (chronic urticaria); and urticaria severity score was removed. - The washout period for prior use of biologics was reduced. - Excluded treatments, medical devices, and/or procedures were updated to clarify the use of systemic corticosteroids, and to exclude H2 antagonists and leukotriene receptor antagonists. - Updated primary objectives and endpoints to clarify the definition of intercurrent events, to add a secondary objective to evaluate the effect of tezepelumab on participants achieving complete control of angioedema disease, and to clarify minimal residual disease endpoints. - The grading scale for adverse events was updated, and laboratory test results were updated to align for grading intensity. - Covariates were updated to clarify the analysis of primary and key secondary endpoints using the baseline score of endpoint. - Updated handling of missing and incomplete data to clarify addressing missing data in binary efficacy endpoints. - Exclusion criteria were updated to clarify QuantiFERON-tuberculosis Gold Plus test requirements and hepatitis-B core antibody testing, only where required by the local country or region.
    30 Sep 2021
    The error in the study schema was rectified.
    26 Apr 2022
    - Number of anti-IgE experienced participants was reduced and interim analysis 2 was added for administrative decision making purposes. The original interim analysis 2, which was a futility analysis was removed. The total number of participants in the primary analysis was reduced. - The number of participants for the anti-IgE experienced cohort was reduced due to limited source of participants. - Objectives and endpoints language was updated in response to regulatory advice regarding HSS7 and ISS7 assessments. - The exclusion criteria were updated to clarify that COVID-19 vaccines were allowed provided that the vaccine was not administered within 7 days before or after any study dosing visit. - Clarified that participants were required to document both HSS and ISS daily with a recall period over 24 hours, and to define that a weekly UAS score represented the sum over a period of 7 days. - Statistical considerations were updated to accommodate changes in number of participants, and to relocate the key secondary endpoints, as well as changes to the multiple testing strategy.

    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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