Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44335   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase III, Randomized, Double-Blind,Placebo-Controlled Study to Assess the Efficacy and Safety of Lebrikizumab in Patients with Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication

    Summary
    EudraCT number
    		 2013-000175-33
    Trial protocol
    		 SK   DE   BE   GB   HU   IT   CZ   PL   ES  
    Global end of trial date
    28 Dec 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    03 Jan 2018
    First version publication date
    03 Jan 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GB28688
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01867125
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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
    28 Dec 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Dec 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Primary purpose of this study is to determine the efficacy and safety of lebrikizumab in subjects with asthma whose disease remains uncontrolled despite daily treatment with inhaled corticosteroid (ICS) therapy and at least one second controller medication. Subjects were randomised in 1:1:1 ratio to receive double-blind treatment with either lebrikizumab ("high" or "low") or placebo, administered subcutaneously (SC) every 4 weeks for 52 weeks, in addition to their standard-of-care therapy. This was followed by a 52-week double-blind active treatment extension. During double-blind active treatment extension period, all subjects received SC injection of lebrikizumab from Week 52 to Week 104. Time on study treatment up to 104 weeks. After study treatment, subjects completed a 20-week safety follow-up.
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 a) Inhaled corticosteroids (ICS) therapy at a total daily dose of 500 − 2000 microgram (mcg) of fluticasone propionate dry powder inhaler (DPI) or equivalent for ≥ 6 months prior to Visit 1, with no changes within 4 weeks prior to Visit 1 and no anticipated changes throughout the study. b) Second controller medication (Long-acting β adrenoceptor agonists (LABA), Leukotriene Receptor Antagonists (LTRA), Long-acting muscarinic antagonists (LAMA), or theophylline) for 6 months prior to Visit 1, with no changes within 4 weeks prior to Visit 1 and no anticipated changes throughout the study (except for theophylline dose, which may be adjusted on the basis of theophylline levels).
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Jul 2013
    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
    Japan: 75
    Country: Number of subjects enrolled
    Korea, Republic of: 19
    Country: Number of subjects enrolled
    Czech Republic: 61
    Country: Number of subjects enrolled
    Hungary: 18
    Country: Number of subjects enrolled
    Poland: 108
    Country: Number of subjects enrolled
    Romania: 18
    Country: Number of subjects enrolled
    Russian Federation: 101
    Country: Number of subjects enrolled
    Serbia: 2
    Country: Number of subjects enrolled
    Slovakia: 30
    Country: Number of subjects enrolled
    Turkey: 14
    Country: Number of subjects enrolled
    Ukraine: 81
    Country: Number of subjects enrolled
    Argentina: 54
    Country: Number of subjects enrolled
    Chile: 14
    Country: Number of subjects enrolled
    Colombia: 3
    Country: Number of subjects enrolled
    Mexico: 9
    Country: Number of subjects enrolled
    Canada: 16
    Country: Number of subjects enrolled
    United States: 312
    Country: Number of subjects enrolled
    Australia: 8
    Country: Number of subjects enrolled
    Belgium: 10
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    France: 16
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    Israel: 48
    Country: Number of subjects enrolled
    Italy: 7
    Country: Number of subjects enrolled
    New Zealand: 6
    Country: Number of subjects enrolled
    South Africa: 34
    Worldwide total number of subjects
    1081
    EEA total number of subjects
    285
    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)
    918
    From 65 to 84 years
    163
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects with asthma, whose disease remained uncontrolled despite daily treatment with inhaled corticosteroid (ICS) therapy and at least one second controller medication, were recruited.in 26 countries.

    Pre-assignment
    Screening details
    		 Subject randomisation was stratified by baseline serum periostin level, history of asthma exacerbations within the last 12 months, baseline asthma medications and country.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Subjects received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period. Subjects then completed a 20-week safety follow-up.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received lebrikizumab matching placebo by SC injection every 4 weeks.

    Arm title
    		 Placebo/Lebrikizumab (37.5 mg)
    Arm description
    		 Subjects received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period followed by SC injection of lebrikizumab at 37.5 mg for another 52 weeks during the active treatment extension period. After study treatment, subjects completed a 20-week safety follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lebrikizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received 37.5 mg lebrikizumab by SC injection every 4 weeks

    Arm title
    		 Placebo/Lebrikizumab (125 mg)
    Arm description
    		 Subjects received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period followed by SC injection of lebrikizumab at 125 mg for another 52 weeks during active treatment extension period. After study treatment, subjects completed a 20-week safety follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lebrikizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received 125 mg lebrikizumab by SC injection every 4 weeks

    Arm title
    		 Lebrikizumab (37.5 mg)
    Arm description
    		 Subjects received SC injection of lebrikizumab (37.5 mg) every 4 weeks for 104 weeks. After study treatment, subjects completed a 20-week safety follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lebrikizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received 37.5 mg lebrikizumab by SC injection every 4 weeks

    Arm title
    		 Lebrikizumab (125 mg)
    Arm description
    		 Subjects received SC injection of lebrikizumab (125 milligrams [mg]) every 4 weeks for 104 weeks. After study treatment, subjects completed a 20-week safety follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lebrikizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received 125 mg lebrikizumab by SC injection every 4 weeks.

    Number of subjects in period 1
    		Placebo Placebo/Lebrikizumab (37.5 mg) Placebo/Lebrikizumab (125 mg) Lebrikizumab (37.5 mg) Lebrikizumab (125 mg)
    Started
    46
    159
    157
    360
    359
    Completed
    10
    139
    139
    302
    285
    Not completed
    36
    20
    18
    58
    74
         Physician decision
    2
    1
    -
    4
    1
         Non-Compliance
    -
    2
    -
    1
    3
         Withdrawal By Subject
    22
    13
    15
    34
    56
         Adverse Event
    5
    -
    2
    5
    6
         Other
    1
    2
    -
    6
    2
         Death
    1
    -
    -
    -
    -
         Lost to follow-up
    4
    2
    1
    6
    4
         Lack of efficacy
    1
    -
    -
    2
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    OVERALL PERIOD
    Reporting group description
    		 -

    Reporting group values
    		 OVERALL PERIOD Total
    Number of subjects
    		 1081 1081
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 51.2 ( 12.6 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 713 713
        Male
    		 368 368

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period. Subjects then completed a 20-week safety follow-up.

    Reporting group title
    Placebo/Lebrikizumab (37.5 mg)
    Reporting group description
    		 Subjects received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period followed by SC injection of lebrikizumab at 37.5 mg for another 52 weeks during the active treatment extension period. After study treatment, subjects completed a 20-week safety follow-up.

    Reporting group title
    Placebo/Lebrikizumab (125 mg)
    Reporting group description
    		 Subjects received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period followed by SC injection of lebrikizumab at 125 mg for another 52 weeks during active treatment extension period. After study treatment, subjects completed a 20-week safety follow-up.

    Reporting group title
    Lebrikizumab (37.5 mg)
    Reporting group description
    		 Subjects received SC injection of lebrikizumab (37.5 mg) every 4 weeks for 104 weeks. After study treatment, subjects completed a 20-week safety follow-up.

    Reporting group title
    Lebrikizumab (125 mg)
    Reporting group description
    		 Subjects received SC injection of lebrikizumab (125 milligrams [mg]) every 4 weeks for 104 weeks. After study treatment, subjects completed a 20-week safety follow-up.

    Subject analysis set title
    Biomarker-High, Placebo
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects in the biomarker high arms had Periostin levels >/= 50 nanograms per millilitre (ng/mL) or Eosinophil counts >/= 300 cells per microlitre (cells/mcL). Subjects in this arm received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period (Period 1).

    Subject analysis set title
    Biomarker-High, Lebrikizumab 37.5 mg
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects in the biomarker high arms had Periostin levels >/= 50 ng/mL or Eosinophil counts >/= 300 cells/mcL. Subjects in this arm received SC injection of lebrikizumab (37.5 mg) every 4 weeks for 52 weeks during the placebo-controlled period (Period 1).

    Subject analysis set title
    Biomarker-High, Lebrikizumab 125 mg
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects in the biomarker high arms had Periostin levels >/= 50 ng/mL or Eosinophil counts >/= 300 cells/mcL. Subjects in this arm received SC injection of lebrikizumab (125 mg) every 4 weeks for 52 weeks during the placebo-controlled period (Period 1).

    Subject analysis set title
    Biomarker-Low, Placebo
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects in the biomarker low arms had Periostin levels < 50 ng/mL and Eosinophils < 300 cells/mcL. Subjects in this arm received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period (Period 1).

    Subject analysis set title
    Biomarker-Low, Lebrikizumab 37.5 mg
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects in the biomarker low arms had Periostin levels < 50 ng/mL and Eosinophils < 300 cells/mcL. Subjects in this arm received SC injection of lebrikizumab (37.5 mg) every 4 weeks for 52 weeks during the placebo-controlled period (Period 1).

    Subject analysis set title
    Biomarker-Low, Lebrikizumab 125 mg
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects in the biomarker low arms had Periostin levels < 50 ng/mL and Eosinophils < 300 cells/mcL. Subjects in this arm received SC injection of lebrikizumab (125 mg) every 4 weeks for 52 weeks during the placebo-controlled period (Period 1).

    Primary: Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period

    		 Close Top of page
    End point title
    		 Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period
    End point description
    An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalisation. Treatment with systemic corticosteroids is defined as treatment with oral, intravenous (IV), or intramuscular (IM) corticosteroids for at least 3 days or an emergency department visit with at least one dose of IV or IM corticosteroids. Reported is the rate of asthma exacerbations during the 52-week placebo-controlled period. ITT population included all subjects randomised in the study.
    End point type
    Primary
    End point timeframe
    Baseline up to 52 weeks
    End point values
    		 Biomarker-High, Placebo Biomarker-High, Lebrikizumab 37.5 mg Biomarker-High, Lebrikizumab 125 mg Biomarker-Low, Placebo Biomarker-Low, Lebrikizumab 37.5 mg Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects analysed
    256
    251
    255
    106
    109
    104
    Units: Exacerbation rate
        number (not applicable)
    0.95
    0.46
    0.66
    0.60
    0.33
    0.44
    Statistical analysis title
    		 High: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Adjusted exacerbation rate ratios are estimates from a Poisson regression model with over-dispersion adjusted for the following covariates in addition to log(patient years) as an offset: number of asthma exacerbations within the last 12 months, baseline asthma medications, geographic region and a 3-level categorical variable (periostin high and eosinophil high, periostin high and eosinophil low, periostin low and eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 125 mg
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0198
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 0.94
    Statistical analysis title
    		 High: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Adjusted exacerbation rate ratios are estimates from a Poisson regression model with over-dispersion adjusted for the following covariates in addition to log(patient years) as an offset: number of asthma exacerbations within the last 12 months, baseline asthma medications, geographic region and a 3-level categorical variable (periostin high and eosinophil high, periostin high and eosinophil low, periostin low and eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    507
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 0.69
    Statistical analysis title
    		 Low: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Adjusted exacerbation rate ratios are estimates from a Poisson regression model with over-dispersion adjusted for the following covariates in addition to log(patient years) as an offset: number of asthma exacerbations within the last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2051
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.44
         upper limit
    		 1.19
    Statistical analysis title
    		 Low: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Adjusted exacerbation rate ratios are estimates from a Poisson regression model with over-dispersion adjusted for the following covariates in addition to log(patient years) as an offset: number of asthma exacerbations within the last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.032
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 0.95

    Secondary: Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52

    		 Close Top of page
    End point title
    		 Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52
    End point description
    FEV1 is the maximal amount of air, which can be forcefully exhaled in one second. Measurements were performed before use of bronchodilator. Reported is the absolute change from baseline in FEV1 to the end of the placebo-controlled period at Week 52. ITT population included all subjects randomised in the study.The value of "n" signifies the number of subjects evaluated at specific time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Biomarker-High, Placebo Biomarker-High, Lebrikizumab 37.5 mg Biomarker-High, Lebrikizumab 125 mg Biomarker-Low, Placebo Biomarker-Low, Lebrikizumab 37.5 mg Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects analysed
    228
    236
    232
    94
    96
    98
    Units: millilitre (mL)
    arithmetic mean (standard deviation)
        Baseline (n= 256, 251, 255,106, 109, 104)
    1795 ( 572 )
    1785 ( 541 )
    1779 ( 588 )
    1982 ( 624 )
    1865 ( 509 )
    1918 ( 517 )
        Change at Week 52 (n= 228, 236, 232, 94, 96, 98)
    110 ( 369 )
    198 ( 412 )
    224 ( 395 )
    23 ( 323 )
    36 ( 282 )
    153 ( 386 )
    Statistical analysis title
    		 High: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Estimates are based on a MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in pre-bronchodilator FEV1 as response variable and included terms for treatment, visit, treatment visit, baseline FEV1, baseline FEV1 visit, number of asthma exacerbations within last 12 months, baseline asthma medications, geographic region and a 3-level categorical variable (periostin high, eosinophil high, periostin high, eosinophil low, periostin low, eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 125 mg
    Number of subjects included in analysis
    460
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0013
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    113
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 44
         upper limit
    		 182
    Variability estimate
    Standard error of the mean
    Dispersion value
    35
    Statistical analysis title
    		 High: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Estimates are based on a MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in pre-bronchodilator FEV1 as response variable and included terms for treatment, visit, treatment visit, baseline FEV1, baseline FEV1 visit, number of asthma exacerbations within last 12 months, baseline asthma medications, geographic region and a 3-level categorical variable (periostin high, eosinophil high, periostin high, eosinophil low, periostin low, eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0034
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    103
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 34
         upper limit
    		 172
    Variability estimate
    Standard error of the mean
    Dispersion value
    35
    Statistical analysis title
    		 Low: Lebrikizumab 125 mg VS Placebo
    Statistical analysis description
    Estimates are based on a MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in pre-bronchodilator FEV1 as response variable and included terms for treatment, visit, treatment visit, baseline FEV1, baseline FEV1 visit, number of asthma exacerbations within last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.007
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    126
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 35
         upper limit
    		 217
    Variability estimate
    Standard error of the mean
    Dispersion value
    46
    Statistical analysis title
    		 Low: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Estimates are based on a MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in pre-bronchodilator FEV1 as response variable and included terms for treatment, visit, treatment visit, baseline FEV1, baseline FEV1 visit, number of asthma exacerbations within last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    190
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7782
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -78
         upper limit
    		 104
    Variability estimate
    Standard error of the mean
    Dispersion value
    46

    Secondary: Time to First Asthma Exacerbation During the Placebo-Controlled Period

    		 Close Top of page
    End point title
    		 Time to First Asthma Exacerbation During the Placebo-Controlled Period
    End point description
    An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalisation. Treatment with systemic corticosteroids is defined as treatment with oral, intravenous (IV), or intramuscular (IM) corticosteroids for at least 3 days or an emergency department visit with at least one dose of IV or IM corticosteroids. Reported is the time to first asthma exacerbation during the 52-week placebo-controlled period. ITT population included all subjects randomised in the study. 9999 = not estimable
    End point type
    Secondary
    End point timeframe
    Baseline up to 52 weeks
    End point values
    		 Biomarker-High, Placebo Biomarker-High, Lebrikizumab 37.5 mg Biomarker-High, Lebrikizumab 125 mg Biomarker-Low, Placebo Biomarker-Low, Lebrikizumab 37.5 mg Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects analysed
    256
    251
    255
    106
    109
    104
    Units: Weeks
        median (confidence interval 95%)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    Statistical analysis title
    		 High: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Hazard ratios were estimated by Cox regression with the following baseline covariates included as stratification factors: number of asthma exacerbations within the last 12 months, baseline asthma medications, geographic region and a 3-level categorical variable (periostin high and eosinophil high, periostin high and eosinophil low, periostin low and eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 125 mg
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0068
    Method
    		 Cox regression
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 0.89
    Statistical analysis title
    		 High: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Hazard ratios were estimated by Cox regression with the following baseline covariates included as stratification factors: number of asthma exacerbations within the last 12 months, baseline asthma medications, geographic region and a 3-level categorical variable (periostin high and eosinophil high, periostin high and eosinophil low, periostin low and eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    507
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0007
    Method
    		 Cox regression
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 0.79
    Statistical analysis title
    		 Low: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Hazard ratios were estimated by Cox regression with the following baseline covariates included as stratification factors: number of asthma exacerbations within the last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0435
    Method
    		 Cox regression
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 0.98
    Statistical analysis title
    		 Low: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Hazard ratios were estimated by Cox regression with the following baseline covariates included as stratification factors: number of asthma exacerbations within the last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0435
    Method
    		 Cox regression
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3
         upper limit
    		 0.89

    Secondary: Rate of Urgent Asthma-Related Health Care Utilization (HCU)

    		 Close Top of page
    End point title
    		 Rate of Urgent Asthma-Related Health Care Utilization (HCU)
    End point description
    Urgent health care utilization was defined as hospitalisations, emergency department visits, and acute care visits. Reported is the rate of urgent asthma-related health care utilization during the 52-week placebo-controlled period. ITT population included all subjects randomised in the study.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    End point values
    		 Biomarker-High, Placebo Biomarker-High, Lebrikizumab 37.5 mg Biomarker-High, Lebrikizumab 125 mg Biomarker-Low, Placebo Biomarker-Low, Lebrikizumab 37.5 mg Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects analysed
    256
    251
    255
    106
    109
    104
    Units: HCU event rate
        number (not applicable)
    0.58
    0.24
    0.62
    0.29
    0.41
    0.20
    Statistical analysis title
    		 High: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Adjusted health care utilization rates and rate ratios are estimates from a Poisson regression model with over-dispersion and adjusted for the following covariates in addition to log(patient years) as an offset: number of asthma exacerbations within the last 12 months, baseline asthma medications, geographic region and a 3-level categorical variable (periostin high and eosinophil high, periostin high and eosinophil low, periostin low and eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 125 mg
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7757
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.63
    Statistical analysis title
    		 High: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Adjusted health care utilization rates and rate ratios are estimates from a Poisson regression model with over-dispersion and adjusted for the following covariates in addition to log(patient years) as an offset: number of asthma exacerbations within the last 12 months, baseline asthma medications, geographic region and a 3-level categorical variable (periostin high and eosinophil high, periostin high and eosinophil low, periostin low and eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    507
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0023
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.24
         upper limit
    		 0.73
    Statistical analysis title
    		 Low: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Adjusted health care utilization rates and rate ratios are estimates from a Poisson regression model with over-dispersion and adjusted for the following covariates in addition to log(patient years) as an offset: number of asthma exacerbations within the last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects included in analysis
    210
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.31
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 1.42
    Statistical analysis title
    		 Low: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Adjusted health care utilization rates and rate ratios are estimates from a Poisson regression model with over-dispersion and adjusted for the following covariates in addition to log(patient years) as an offset: number of asthma exacerbations within the last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2725
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    1.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 2.6

    Secondary: Change From Baseline in Standardized Asthma Quality of Life Questionnaire (AQLQ) Score at Week 52

    		 Close Top of page
    End point title
    		 Change From Baseline in Standardized Asthma Quality of Life Questionnaire (AQLQ) Score at Week 52
    End point description
    Asthma-specific health-related quality of life was assessed by the overall score of the Standardized AQLQ. The AQLQ is a self-administered test with 32 questions; each with seven possible answers ranging from 1 to 7 with a higher score being more favourable. Total score is calculated as follows: sum of items 1to 32 divided by 32 for a score range of 1 to 7 with a higher score indicating a better outcome. Reported is the change in AQLQ score from baseline to the end of the placebo-controlled period at Week 52. ITT population included all subjects randomised in the study.The value of "n" signifies the number of subjects evaluated at specific time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Biomarker-High, Placebo Biomarker-High, Lebrikizumab 37.5 mg Biomarker-High, Lebrikizumab 125 mg Biomarker-Low, Placebo Biomarker-Low, Lebrikizumab 37.5 mg Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects analysed
    230
    236
    230
    94
    97
    99
    Units: Score on scale
    arithmetic mean (standard deviation)
        Baseline (n= 256, 251, 254,106, 109, 104)
    4.23 ( 1.04 )
    4.15 ( 1.04 )
    4.16 ( 1.04 )
    4.06 ( 1.12 )
    4.22 ( 1.17 )
    4.23 ( 0.96 )
        Change at Week 52 (n= 230, 236, 230, 94, 97, 99)
    0.76 ( 1.01 )
    0.93 ( 1.12 )
    0.91 ( 1.19 )
    0.86 ( 1.09 )
    0.74 ( 1.12 )
    0.85 ( 1.11 )
    Statistical analysis title
    		 High: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Estimates are based on a MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in AQLQ(S) score as response variable and included terms for treatment, visit, treatment visit, baseline AQLQ(S), baseline AQLQ(S) visit, number of asthma exacerbations within last 12 months, baseline asthma medications, geographic region and a 3-level categorical variable (periostin high, eosinophil high, periostin high, eosinophil low, periostin low, eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 125 mg
    Number of subjects included in analysis
    460
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1533
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 0.31
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Statistical analysis title
    		 High: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Estimates are based on a MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in AQLQ(S) score as response variable and included terms for treatment, visit, treatment visit, baseline AQLQ(S), baseline AQLQ(S) visit, number of asthma exacerbations within last 12 months, baseline asthma medications, geographic region and a 3-level categorical variable (periostin high, eosinophil high, periostin high, eosinophil low, periostin low, eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    466
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1032
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Statistical analysis title
    		 Low: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Estimates are based on a MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in AQLQ(S) score as response variable and included terms for treatment, visit, treatment visit, baseline AQLQ(S), baseline AQLQ(S) visit, number of asthma exacerbations within last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects included in analysis
    193
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9293
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.26
         upper limit
    		 0.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.138
    Statistical analysis title
    		 Low: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Estimates are based on a MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in AQLQ(S) score as response variable and included terms for treatment, visit, treatment visit, baseline AQLQ(S), baseline AQLQ(S) visit, number of asthma exacerbations within last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    191
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4015
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.38
         upper limit
    		 0.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.137

    Secondary: Change from Baseline In Asthma Rescue Medication at Week 52

    		 Close Top of page
    End point title
    		 Change from Baseline In Asthma Rescue Medication at Week 52
    End point description
    Reported here is the change in the number of puffs or nebulized treatments of asthma rescue medication from baseline to the end of the placebo-controlled period at Week 52. ITT population included all subjects randomised in the study.The value of "n" signifies the number of subjects evaluated at specific time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Biomarker-High, Placebo Biomarker-High, Lebrikizumab 37.5 mg Biomarker-High, Lebrikizumab 125 mg Biomarker-Low, Placebo Biomarker-Low, Lebrikizumab 37.5 mg Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects analysed
    227
    234
    232
    91
    96
    94
    Units: Puffs per day
    arithmetic mean (standard deviation)
        Baseline (n= 256, 251, 254, 106, 109, 103)
    3.0 ( 3.8 )
    2.7 ( 2.9 )
    3.0 ( 3.9 )
    3.1 ( 4.1 )
    2.9 ( 2.9 )
    3.4 ( 5.2 )
        Change at Week 52 (n= 227, 234, 232, 91, 96, 94)
    -0.5 ( 2.9 )
    -1.0 ( 2.3 )
    -1.3 ( 3.3 )
    -0.9 ( 2.2 )
    -0.7 ( 2.3 )
    -1.4 ( 4.8 )
    Statistical analysis title
    		 High: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Estimates are based on MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in asthma rescue medication use as response variable and included terms for treatment, visit, treatment visit, baseline rescue medication use/visit, number of asthma exacerbations within last 12 months, baseline asthma medications, geographic region and 3-level categorical variable (periostin high, eosinophil high, periostin high, eosinophil low, periostin low, eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 125 mg
    Number of subjects included in analysis
    459
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0121
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Statistical analysis title
    		 High: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Estimates are based on MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in asthma rescue medication use as response variable and included terms for treatment, visit, treatment visit, baseline rescue medication use/visit, number of asthma exacerbations within last 12 months, baseline asthma medications, geographic region and 3-level categorical variable (periostin high, eosinophil high, periostin high, eosinophil low, periostin low, eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    461
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0256
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    Statistical analysis title
    		 Low: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Estimates are based on MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in asthma rescue medication use as response variable and included terms for treatment, visit, treatment visit, baseline rescue medication use/visit, number of asthma exacerbations within last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2698
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3
    Statistical analysis title
    		 Low: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Estimates are based on MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in asthma rescue medication use as response variable and included terms for treatment, visit, treatment visit, baseline rescue medication use/visit, number of asthma exacerbations within last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    187
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.934
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3

    Secondary: Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Week 52

    		 Close Top of page
    End point title
    		 Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Week 52
    End point description
    The ACQ-5 is test with 5 questions; each with seven possible answers ranging from 0 to 6 with a lower score being more favourable. Total score range is 0 to 30 with a lower score indicating a better outcome. Reported is the change in ACQ-5 score from baseline to the end of the placebo-controlled period at Week 52. ITT population included all subjects randomised in the study.The value of "n" signifies the number of subjects evaluated at specific time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Biomarker-High, Placebo Biomarker-High, Lebrikizumab 37.5 mg Biomarker-High, Lebrikizumab 125 mg Biomarker-Low, Placebo Biomarker-Low, Lebrikizumab 37.5 mg Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects analysed
    229
    235
    230
    93
    97
    99
    Units: Score on scale
    arithmetic mean (standard deviation)
        Baseline (n= 256, 251, 255, 106, 109, 104)
    2.7 ( 0.7 )
    2.6 ( 0.7 )
    2.6 ( 0.7 )
    2.7 ( 0.9 )
    2.6 ( 0.7 )
    2.6 ( 0.7 )
        Change at Week 52 (n= 229, 235, 230, 93, 97, 99)
    -0.8 ( 1.0 )
    -0.9 ( 1.1 )
    -0.9 ( 1.1 )
    -0.8 ( 1.0 )
    -0.8 ( 1.0 )
    -0.8 ( 1.0 )
    Statistical analysis title
    		 High: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Estimates are based on MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in ACQ-5 as response variable and included terms for treatment, visit, treatment visit, baseline ACQ-5, baseline ACQ-5 visit, number of asthma exacerbations within the last 12 months, baseline asthma medications, geographic region and 3-level categorical variable (periostin high, eosinophil high, periostin high, eosinophil low, periostin low,eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 125 mg
    Number of subjects included in analysis
    459
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4018
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Statistical analysis title
    		 High: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Estimates are based on MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in ACQ-5 as response variable and included terms for treatment, visit, treatment visit, baseline ACQ-5, baseline ACQ-5 visit, number of asthma exacerbations within the last 12 months, baseline asthma medications, geographic region and 3-level categorical variable (periostin high, eosinophil high, periostin high, eosinophil low, periostin low,eosinophil high).
    Comparison groups
    Biomarker-High, Placebo v Biomarker-High, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    464
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2341
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Statistical analysis title
    		 Low: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Estimates are based on MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in ACQ-5 as response variable and included terms for treatment, visit, treatment visit, baseline ACQ-5, baseline ACQ-5 visit, number of asthma exacerbations within the last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 125 mg
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9293
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13
    Statistical analysis title
    		 Low: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Estimates are based on MMRM analysis with an unstructured covariance matrix. Model used absolute change from baseline in ACQ-5 as response variable and included terms for treatment, visit, treatment visit, baseline ACQ-5, baseline ACQ-5 visit, number of asthma exacerbations within the last 12 months, baseline asthma medications and geographic region.
    Comparison groups
    Biomarker-Low, Placebo v Biomarker-Low, Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    190
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9787
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.13

    Other pre-specified: Percentage of Subjects With Anti-Therapeutic Antibodies to Lebrikizumab

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Anti-Therapeutic Antibodies to Lebrikizumab
    End point description
    The safety population included all subjects who received at least one dose of study medication.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to Week 124 (assessed at Baseline, Weeks 4, 12, 24, 36, 52 and safety follow-up [20 weeks] or end of study)
    End point values
    		 Placebo Placebo/Lebrikizumab (37.5 mg) Placebo/Lebrikizumab (125 mg) Lebrikizumab (37.5 mg) Lebrikizumab (125 mg)
    Number of subjects analysed
    43
    159
    157
    359
    358
    Units: Percentage of Subjects
        number (not applicable)
    0
    11.3
    10.8
    18.7
    15.1
    No statistical analyses for this end point

    Other pre-specified: Percentage of Subjects With Adverse Events

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Adverse Events
    End point description
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. The safety population included all subjects who received at least one dose of study medication.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Week 124
    End point values
    		 Placebo Placebo/Lebrikizumab (37.5 mg) Placebo/Lebrikizumab (125 mg) Lebrikizumab (37.5 mg) Lebrikizumab (125 mg)
    Number of subjects analysed
    46
    159
    157
    360
    359
    Units: Percentage of Subjects
        number (not applicable)
    80.4
    91.2
    91.7
    93.1
    90.0
    No statistical analyses for this end point

    Other pre-specified: Minimum Serum Concentration (Cmin) of Lebrikizumab

    		 Close Top of page
    End point title
    		 Minimum Serum Concentration (Cmin) of Lebrikizumab [1]
    End point description
    ITT population included all subjects randomised in the study.
    End point type
    Other pre-specified
    End point timeframe
    Predose (0 hour) at Weeks 4, 12, 24, 36, and 52
    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: Minimum serum concentration of lebrikizumab was only measured in the arm that received lebrikizumab treatment. Therefore, data are only reported for the lebrikizumab arm.
    End point values
    		 Lebrikizumab (37.5 mg) Lebrikizumab (125 mg)
    Number of subjects analysed
    360
    359
    Units: microgram per millilitre (mcg/mL)
    arithmetic mean (standard deviation)
        Week 4: (n= 360, 359)
    2.40 ( 1.67 )
    8.47 ( 3.61 )
        Week 12: (n= 360, 359)
    3.78 ( 2.21 )
    14.1 ( 6.17 )
        Week 24: (n=360, 359)
    4.38 ( 2.28 )
    16.4 ( 7.78 )
        Week 36: (n=360, 359)
    4.87 ( 3.12 )
    16.7 ( 7.62 )
        Week 52: (n= 360, 359)
    4.66 ( 2.94 )
    16.9 ( 8.28 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 124 weeks
    Adverse event reporting additional description
    Safety population included all subjects who received at least one dose of study medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period. Subjects then completed a 20-week safety follow-up.

    Reporting group title
    Placebo/Lebrikizumab (37.5 mg)
    Reporting group description
    		 Subjects received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period and then SC injection of lebrikizumab at 37.5 mg for 52 weeks during the active treatment extension period. After study treatment, subjects completed a 20-week safety follow-up.

    Reporting group title
    Placebo/Lebrikizumab (125 mg)
    Reporting group description
    		 Subjects received SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during the placebo-controlled period and then SC injection of lebrikizumab at 125 mg for 52 weeks during active treatment extension period. After study treatment, subjects completed a 20-week safety follow-up.

    Reporting group title
    Lebrikizumab (37.5 mg)
    Reporting group description
    		 Subjects received SC injection of lebrikizumab (37.5 mg) every 4 weeks for 104 weeks. After study treatment, subjects completed a 20-week safety follow-up.

    Reporting group title
    Lebrikizumab (125 mg)
    Reporting group description
    		 Subjects received SC injection of lebrikizumab (125 milligrams [mg]) every 4 weeks for 104 weeks. After study treatment, subjects completed a 20-week safety follow-up.

    Serious adverse events
    		 Placebo Placebo/Lebrikizumab (37.5 mg) Placebo/Lebrikizumab (125 mg) Lebrikizumab (37.5 mg) Lebrikizumab (125 mg)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 46 (19.57%)
    21 / 159 (13.21%)
    27 / 157 (17.20%)
    48 / 360 (13.33%)
    49 / 359 (13.65%)
         number of deaths (all causes)
    1
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of the cervix
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Basal cell carcinoma
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Colon adenoma
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Meningioma
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Ovarian cancer
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Uterine leiomyoma
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Hypertension
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Hypertensive emergency
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Surgical and medical procedures
    Hysterosalpingectomy
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Parathyroidectomy
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Tooth extraction
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical incompetence
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    2 / 360 (0.56%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillitis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Metrorrhagia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystocele
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Endometriosis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Ovarian cyst ruptured
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Cervical polyp
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    4 / 46 (8.70%)
    3 / 159 (1.89%)
    6 / 157 (3.82%)
    12 / 360 (3.33%)
    11 / 359 (3.06%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 6
    0 / 13
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eosinophilic pneumonia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Hypoxia
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Acute respiratory failure
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Hydrothorax
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Organising pneumonia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Psychiatric disorders
    Mental disorder
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Investigations
    Eosinophil count increased
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Weight decreased
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Injury, poisoning and procedural complications
    Tendon rupture
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 46 (0.00%)
    2 / 159 (1.26%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Contusion
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Fall
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Fascial rupture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Foot fracture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Humerus fracture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Incarcerated incisional hernia
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Lower limb fracture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Meniscus injury
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Muscle rupture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Radius fracture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Road traffic accident
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Thermal burn
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Ulna fracture
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Wound dehiscence
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    2 / 360 (0.56%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    2 / 359 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Atrial flutter
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Cardiac failure acute
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Coronary artery stenosis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Mitral valve incompetence
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Myocardial infarction
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Tachycardia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    2 / 157 (1.27%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid sinus syndrome
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Nervous system disorder
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Neuralgia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Radicular pain
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Visual field defect
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Eosinophilia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Diarrhoea
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Epiploic appendagitis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastric volvulus
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Hiatus hernia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Inguinal hernia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Pancreatitis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Pancreatitis acute
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Umbilical hernia
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    3 / 360 (0.83%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Cholecystitis acute
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Jaundice cholestatic
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Skin and subcutaneous tissue disorders
    Psoriasis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Urticaria
         subjects affected / exposed
    1 / 46 (2.17%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Renal and urinary disorders
    Renal aneurysm
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    2 / 157 (1.27%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthropathy
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Osteochondrosis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Osteonecrosis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Pain in extremity
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Rhabdomyolysis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scoliosis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Trigger finger
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 46 (0.00%)
    4 / 159 (2.52%)
    0 / 157 (0.00%)
    4 / 360 (1.11%)
    2 / 359 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
    0 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Respiratory tract infection
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    2 / 157 (1.27%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 46 (0.00%)
    2 / 159 (1.26%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    2 / 359 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Encephalitis
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Escherichia infection
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastroenteritis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Meningitis
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Peritonsillar abscess
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Cellulitis
         subjects affected / exposed
    0 / 46 (0.00%)
    2 / 159 (1.26%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 46 (0.00%)
    1 / 159 (0.63%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Staphylococcal infection
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Tuberculosis of peripheral lymph nodes
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    1 / 360 (0.28%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Varicella
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    0 / 157 (0.00%)
    0 / 360 (0.00%)
    1 / 359 (0.28%)
         occurrences causally related to treatment / all
    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
    Viral infection
         subjects affected / exposed
    0 / 46 (0.00%)
    0 / 159 (0.00%)
    1 / 157 (0.64%)
    0 / 360 (0.00%)
    0 / 359 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Placebo/Lebrikizumab (37.5 mg) Placebo/Lebrikizumab (125 mg) Lebrikizumab (37.5 mg) Lebrikizumab (125 mg)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    26 / 46 (56.52%)
    134 / 159 (84.28%)
    131 / 157 (83.44%)
    298 / 360 (82.78%)
    292 / 359 (81.34%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 46 (4.35%)
    8 / 159 (5.03%)
    4 / 157 (2.55%)
    11 / 360 (3.06%)
    8 / 359 (2.23%)
         occurrences all number
    2
    8
    5
    11
    10
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 46 (2.17%)
    13 / 159 (8.18%)
    8 / 157 (5.10%)
    15 / 360 (4.17%)
    14 / 359 (3.90%)
         occurrences all number
    1
    15
    8
    20
    14
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 46 (13.04%)
    18 / 159 (11.32%)
    12 / 157 (7.64%)
    34 / 360 (9.44%)
    29 / 359 (8.08%)
         occurrences all number
    9
    27
    62
    74
    116
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    1 / 46 (2.17%)
    1 / 159 (0.63%)
    2 / 157 (1.27%)
    11 / 360 (3.06%)
    18 / 359 (5.01%)
         occurrences all number
    1
    1
    7
    35
    75
    Fatigue
         subjects affected / exposed
    3 / 46 (6.52%)
    4 / 159 (2.52%)
    2 / 157 (1.27%)
    3 / 360 (0.83%)
    4 / 359 (1.11%)
         occurrences all number
    3
    5
    2
    3
    4
    Injection site pain
         subjects affected / exposed
    0 / 46 (0.00%)
    4 / 159 (2.52%)
    11 / 157 (7.01%)
    4 / 360 (1.11%)
    6 / 359 (1.67%)
         occurrences all number
    0
    9
    19
    7
    6
    Gastrointestinal disorders
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 46 (0.00%)
    8 / 159 (5.03%)
    3 / 157 (1.91%)
    9 / 360 (2.50%)
    9 / 359 (2.51%)
         occurrences all number
    0
    8
    3
    11
    9
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    16 / 46 (34.78%)
    83 / 159 (52.20%)
    93 / 157 (59.24%)
    156 / 360 (43.33%)
    184 / 359 (51.25%)
         occurrences all number
    31
    251
    241
    395
    472
    Rhinitis allergic
         subjects affected / exposed
    2 / 46 (4.35%)
    9 / 159 (5.66%)
    11 / 157 (7.01%)
    24 / 360 (6.67%)
    8 / 359 (2.23%)
         occurrences all number
    2
    11
    15
    35
    9
    Cough
         subjects affected / exposed
    1 / 46 (2.17%)
    5 / 159 (3.14%)
    7 / 157 (4.46%)
    18 / 360 (5.00%)
    18 / 359 (5.01%)
         occurrences all number
    1
    5
    9
    21
    20
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 46 (2.17%)
    11 / 159 (6.92%)
    11 / 157 (7.01%)
    22 / 360 (6.11%)
    24 / 359 (6.69%)
         occurrences all number
    1
    11
    12
    23
    30
    Arthralgia
         subjects affected / exposed
    2 / 46 (4.35%)
    12 / 159 (7.55%)
    7 / 157 (4.46%)
    15 / 360 (4.17%)
    20 / 359 (5.57%)
         occurrences all number
    2
    13
    8
    19
    25
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 46 (4.35%)
    39 / 159 (24.53%)
    38 / 157 (24.20%)
    72 / 360 (20.00%)
    81 / 359 (22.56%)
         occurrences all number
    4
    64
    62
    117
    135
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 46 (6.52%)
    17 / 159 (10.69%)
    26 / 157 (16.56%)
    59 / 360 (16.39%)
    67 / 359 (18.66%)
         occurrences all number
    3
    33
    45
    94
    112
    Bronchitis
         subjects affected / exposed
    1 / 46 (2.17%)
    23 / 159 (14.47%)
    20 / 157 (12.74%)
    60 / 360 (16.67%)
    48 / 359 (13.37%)
         occurrences all number
    2
    30
    37
    85
    84
    Sinusitis
         subjects affected / exposed
    1 / 46 (2.17%)
    13 / 159 (8.18%)
    13 / 157 (8.28%)
    26 / 360 (7.22%)
    34 / 359 (9.47%)
         occurrences all number
    1
    21
    19
    35
    51
    Pharyngitis
         subjects affected / exposed
    0 / 46 (0.00%)
    12 / 159 (7.55%)
    13 / 157 (8.28%)
    20 / 360 (5.56%)
    19 / 359 (5.29%)
         occurrences all number
    0
    12
    17
    21
    20
    Rhinitis
         subjects affected / exposed
    0 / 46 (0.00%)
    3 / 159 (1.89%)
    16 / 157 (10.19%)
    24 / 360 (6.67%)
    20 / 359 (5.57%)
         occurrences all number
    0
    3
    28
    42
    28
    Influenza
         subjects affected / exposed
    1 / 46 (2.17%)
    8 / 159 (5.03%)
    4 / 157 (2.55%)
    28 / 360 (7.78%)
    21 / 359 (5.85%)
         occurrences all number
    2
    9
    4
    34
    30
    Urinary tract infection
         subjects affected / exposed
    0 / 46 (0.00%)
    9 / 159 (5.66%)
    9 / 157 (5.73%)
    15 / 360 (4.17%)
    21 / 359 (5.85%)
         occurrences all number
    0
    10
    10
    17
    26
    Respiratory tract infection viral
         subjects affected / exposed
    2 / 46 (4.35%)
    8 / 159 (5.03%)
    4 / 157 (2.55%)
    22 / 360 (6.11%)
    9 / 359 (2.51%)
         occurrences all number
    2
    10
    7
    30
    17
    Pneumonia
         subjects affected / exposed
    0 / 46 (0.00%)
    9 / 159 (5.66%)
    2 / 157 (1.27%)
    8 / 360 (2.22%)
    8 / 359 (2.23%)
         occurrences all number
    0
    10
    3
    8
    8
    Respiratory tract Infection
         subjects affected / exposed
    0 / 46 (0.00%)
    7 / 159 (4.40%)
    8 / 157 (5.10%)
    11 / 360 (3.06%)
    6 / 359 (1.67%)
         occurrences all number
    0
    8
    12
    20
    9

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Sep 2015
    The protocol was amended for the following reasons: 1) to update the description of completed clinical trials with lebrikizumab, 2) to add blood eosinophil count in the biomarker objective, 3) to update the biomarker subgroups for analysis to include blood eosinophil count, 4) to update the secondary efficacy endpoints, and 5) to update details of the statistical analyses.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 09 16:11:31 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA