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    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
    		 2013-000176-15
    Trial protocol
    		 DE   BE   GB   HU   IT   CZ   ES   PL   BG   SK  
    Global end of trial date
    03 Jan 2017

    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
    GB28689
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01868061
    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
    03 Jan 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Jan 2017
    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 as subcutaneous (SC) injection 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. Subjects who were assigned to placebo during the placebo-controlled period of the trial were re-randomised at Week 52 to receive blinded SC lebrikizumab 37.5 milligrams (mg) or 125 mg every 4 weeks 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
    29 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: 56
    Country: Number of subjects enrolled
    Korea, Republic of: 30
    Country: Number of subjects enrolled
    Bulgaria: 82
    Country: Number of subjects enrolled
    Czech Republic: 14
    Country: Number of subjects enrolled
    Hungary: 11
    Country: Number of subjects enrolled
    Poland: 140
    Country: Number of subjects enrolled
    Romania: 19
    Country: Number of subjects enrolled
    Russian Federation: 64
    Country: Number of subjects enrolled
    Serbia: 10
    Country: Number of subjects enrolled
    Slovakia: 14
    Country: Number of subjects enrolled
    Ukraine: 95
    Country: Number of subjects enrolled
    Argentina: 21
    Country: Number of subjects enrolled
    Mexico: 20
    Country: Number of subjects enrolled
    Peru: 42
    Country: Number of subjects enrolled
    Canada: 20
    Country: Number of subjects enrolled
    United States: 297
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    Belgium: 13
    Country: Number of subjects enrolled
    Spain: 21
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    Israel: 32
    Country: Number of subjects enrolled
    Italy: 7
    Country: Number of subjects enrolled
    New Zealand: 8
    Country: Number of subjects enrolled
    South Africa: 33
    Worldwide total number of subjects
    1067
    EEA total number of subjects
    332
    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)
    909
    From 65 to 84 years
    158
    85 years and over
    0

    Subject disposition

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    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
    		 Subject, Investigator

    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
    RO5490255
    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
    RO5490255
    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
    RO5490255
    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 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
    RO5490255
    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
    44
    156
    154
    356
    357
    Completed
    14
    139
    140
    291
    292
    Not completed
    30
    17
    14
    65
    65
         Physician decision
    1
    -
    -
    2
    1
         Non-Compliance
    2
    -
    -
    -
    2
         Withdrawal By Subject
    18
    10
    8
    51
    42
         Adverse Event
    3
    1
    4
    1
    8
         Death
    -
    -
    -
    1
    -
         Pregnancy
    -
    -
    -
    1
    -
         Lost to follow-up
    2
    5
    2
    6
    6
         Reason not specified
    3
    -
    -
    3
    4
         Lack of efficacy
    1
    1
    -
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Period
    Reporting group description
    		 -

    Reporting group values
    		 Overall Period Total
    Number of subjects
    		 1067
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 50.2 ± 13.0 -
    Gender Categorical
    Units: Subjects
        Female
    		 658 658
        Male
    		 409 409

    End points

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    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 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) and 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

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    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
    247
    257
    251
    107
    99
    106
    Units: Exacerbation rate
        number (not applicable)
    0.73
    0.54
    0.54
    0.34
    0.50
    0.35
    Statistical analysis title
    		 High: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Adjusted exacerbation rates and 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
    498
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0571
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.01
    Statistical analysis title
    		 High: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Adjusted exacerbation rates and 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
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.056
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.01
    Statistical analysis title
    		 Low: Lebrikizumab 125 mg vs Placebo
    Statistical analysis description
    Adjusted exacerbation rates and 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
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9099
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 1.78
    Statistical analysis title
    		 Low: Lebrikizumab 37.5 mg vs Placebo
    Statistical analysis description
    Adjusted exacerbation rates and 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
    206
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1462
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    1.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 2.45

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

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    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.
    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
    226
    241
    231
    94
    88
    96
    Units: millilitre (mL)
    arithmetic mean (standard deviation)
        Baseline (n=247,257,251,107,99,106)
    1839 ± 573
    1809 ± 515
    1836 ± 599
    1995 ± 577
    1954 ± 593
    1862 ± 537
        Change at Week 52 (n=226,241,231,94,88,96)
    91 ± 383
    184 ± 387
    183 ± 424
    85 ± 422
    98 ± 435
    103 ± 383
    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
    457
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0216
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12
         upper limit
    		 152
    Variability estimate
    Standard error of the mean
    Dispersion value
    36
    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
    467
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0143
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18
         upper limit
    		 157
    Variability estimate
    Standard error of the mean
    Dispersion value
    36
    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
    190
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7456
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -97
         upper limit
    		 135
    Variability estimate
    Standard error of the mean
    Dispersion value
    59
    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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9907
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -117
         upper limit
    		 118
    Variability estimate
    Standard error of the mean
    Dispersion value
    60

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

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    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
    247
    257
    251
    107
    99
    106
    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
    498
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0466
    Method
    		 Cox regression
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 1
    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
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0987
    Method
    		 Cox regression
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 1.05
    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
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8502
    Method
    		 Cox regression
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.65
    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
    206
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2558
    Method
    		 Cox regression
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 2.36

    Secondary: Rate of Urgent Asthma-Related Health Care Utilization (HCU) During the Placebo-Controlled Period

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    End point title
    		 Rate of Urgent Asthma-Related Health Care Utilization (HCU) During the Placebo-Controlled Period
    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
    247
    257
    251
    107
    99
    106
    Units: HCU event rate
        number (not applicable)
    0.45
    0.35
    0.42
    0.30
    0.56
    0.40
    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
    498
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7394
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 1.41
    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
    504
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2612
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 1.21
    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
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4049
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    1.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 2.71
    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
    206
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0553
    Method
    		 Poisson regression
    Parameter type
    		 Rate Ratio
    Point estimate
    1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 3.65

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

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    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.
    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
    226
    240
    229
    93
    87
    96
    Units: Score on scale
    arithmetic mean (standard deviation)
        Baseline (n=246,256,249,106,99,106)
    4.06 ± 0.98
    4.13 ± 0.98
    4.09 ± 0.94
    4.21 ± 1.07
    4.08 ± 1.02
    3.98 ± 0.98
        Change at Week 52 (n=226,240,229,93,87,96)
    0.83 ± 1.03
    0.81 ± 1.06
    1.06 ± 1.11
    0.63 ± 1.07
    0.80 ± 1.11
    0.68 ± 1.00
    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
    455
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0057
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.07
         upper limit
    		 0.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.091
    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
    		 = 0.9227
    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
    		 -0.17
         upper limit
    		 0.19
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.091
    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
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5859
    Method
    		 Mixed Model Repeated Measures (MMRM)
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.36
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.143
    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
    180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4807
    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
    		 -0.18
         upper limit
    		 0.39
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.146

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

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    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.
    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
    222
    238
    225
    90
    83
    93
    Units: Puffs per day
    arithmetic mean (standard deviation)
        Baseline (n=247,256,250,107,99,105)
    3.0 ± 3.0
    3.0 ± 3.5
    3.5 ± 4.5
    3.0 ± 3.0
    2.9 ± 2.4
    2.7 ± 2.3
        Change at Week 52 (n=222,238,225,90,83,93)
    -0.4 ± 2.8
    -1.0 ± 2.4
    -1.2 ± 3.0
    -0.3 ± 2.0
    -0.7 ± 1.6
    -0.5 ± 1.5
    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
    447
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0099
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         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
    460
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0451
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0
    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
    183
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5236
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2
    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
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1851
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2

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

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    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.
    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
    224
    240
    230
    93
    87
    96
    Units: Score on scale
    arithmetic mean (standard deviation)
        Baseline (n=246,256,250,106,99,106)
    2.8 ± 0.7
    2.7 ± 0.7
    2.7 ± 0.7
    2.7 ± 0.7
    2.8 ± 0.8
    2.8 ± 0.7
        Change at Week 52 (n=224,240,230,93,87,96)
    -0.8 ± 1.0
    -0.8 ± 1.0
    -1.0 ± 1.1
    -0.7 ± 0.9
    -0.8 ± 1.0
    -0.7 ± 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
    454
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.097
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 0
    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
    		 = 0.9071
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.2
    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
    189
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8885
    Method
    		 Mixed Model Repeated Measures
    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
    180
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3466
    Method
    		 Mixed Model Repeated Measures
    Parameter type
    		 Difference in Adjusted Mean
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.14

    Secondary: Percentage of Subjects With Adverse Events

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    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
    Secondary
    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
    44 [1]
    155
    154
    356
    357
    Units: Percentage of subjects
        number (not applicable)
    71.1
    90.3
    85.1
    82.0
    83.2
    Notes
    [1] - Safety population actual n=45 due to transfer of subject from other arm.
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Anti-Therapeutic Antibodies to Lebrikizumab

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    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
    Secondary
    End point timeframe
    Baseline up to Week 124 (assessed at Baseline, Weeks 4, 12, 24, 36, 52 and Safety Follow-up Week 20 [or end of the 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
    44 [2]
    155
    154
    354
    356
    Units: Percentage of subjects
        number (not applicable)
    0
    11.6
    8.4
    16.1
    14.0
    Notes
    [2] - Safety population n=45 for this arm due to transfer from other arm.
    No statistical analyses for this end point

    Secondary: Minimum Serum Concentration (Cmin ) of Lebrikizumab

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    End point title
    		 Minimum Serum Concentration (Cmin ) of Lebrikizumab [3]
    End point description
    ITT population included all subjects randomised in the study. 9999 = not reportable (when more than one third of values were lower than reportable, which was set to 0.045 mcg/mL).
    End point type
    Secondary
    End point timeframe
    Predose (0 hour) at Weeks 4, 12, 24, 36, and 52
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 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
    348
    344
    Units: microgram per millilitre (mcg/mL)
    arithmetic mean (standard deviation)
        Week 4 (n=1, 0, 348, 344)
    2.74 ± 2.25
    8.67 ± 3.82
        Week 12 (n=0, 1, 339, 342)
    4.44 ± 2.96
    15.5 ± 6.60
        Week 24 (n=0, 0, 327, 335)
    4.28 ± 3.06
    16.0 ± 7.73
        Week 36 (n=0, 2, 325, 322)
    4.51 ± 2.81
    17.0 ± 8.86
        Week 52 (n=0, 0, 320, 314)
    4.59 ± 3.15
    17.3 ± 8.80
    No statistical analyses for this end point

    Adverse events

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    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
    11 / 45 (24.44%)
    22 / 155 (14.19%)
    24 / 154 (15.58%)
    56 / 356 (15.73%)
    57 / 357 (15.97%)
         number of deaths (all causes)
    0
    0
    1
    1
    1
         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 / 45 (0.00%)
    1 / 155 (0.65%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    1 / 356 (0.28%)
    0 / 357 (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
    Uterine leiomyoma
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    1 / 357 (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
    Adenocarcinoma gastric
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Basal cell carcinoma
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Bladder neoplasm
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Bowen's disease
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Endometrial cancer
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Gastric cancer
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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 / 1
    Lipoma
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Metastases to lung
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Prostate cancer
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Uterine cancer
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Vocal cord neoplasm
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    2 / 357 (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
    Hypertension
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Subclavian vein thrombosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Varicose vein
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Surgical and medical procedures
    Abortion induced
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    2 / 356 (0.56%)
    1 / 357 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abortion threatened
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Ectopic pregnancy
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Imminent abortion
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    1 / 45 (2.22%)
    1 / 155 (0.65%)
    1 / 154 (0.65%)
    1 / 356 (0.28%)
    1 / 357 (0.28%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Cyst
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Drug hypersensitivity
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Sarcoidosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Reproductive system and breast disorders
    Uterine prolapse
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    1 / 356 (0.28%)
    0 / 357 (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
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Ovarian cyst
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    5 / 45 (11.11%)
    8 / 155 (5.16%)
    4 / 154 (2.60%)
    18 / 356 (5.06%)
    19 / 357 (5.32%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 15
    0 / 7
    0 / 25
    0 / 23
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 155 (0.65%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Dysphonia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Eosinophilic pneumonia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Hydrothorax
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Nasal polyps
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Pleural effusion
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Pulmonary hilar enlargement
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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 failure
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Status asthmaticus
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 155 (0.65%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Acute psychosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Completed suicide
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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 / 1
    0 / 0
    0 / 0
    Depression suicidal
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Hallucination
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Blood pressure increased
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Foot fracture
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 155 (0.65%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Humerus fracture
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    1 / 357 (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
    Rib fracture
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    1 / 357 (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
    Upper limb fracture
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    2 / 357 (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
    Chest injury
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Fibula fracture
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Hand fracture
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Head injury
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 155 (0.65%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Overdose
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Patella fracture
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Road traffic accident
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Tibia fracture
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Scapula fracture
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Wound
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 155 (0.65%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Atrial fibrillation
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    1 / 356 (0.28%)
    1 / 357 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    1 / 357 (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
    Myocardial infarction
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    1 / 356 (0.28%)
    0 / 357 (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
    Atrial flutter
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Cardiac failure congestive
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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 / 1
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Coronary artery disease
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Coronary artery insufficiency
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 155 (0.65%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Coronary artery occlusion
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Mitral valve incompetence
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Myocardial ischaemia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Palpitations
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 155 (0.65%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Tachycardia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    2 / 356 (0.56%)
    2 / 357 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Memory impairment
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Myoclonus
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Neuropathy peripheral
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Pschyogenic pseudosyncope
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Seizure
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Syncope
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Blood and lymphatic system disorders
    Aplastic anaemia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Eosinophilia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Leukocytosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Gastrointestinal disorders
    Inguinal hernia
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 155 (1.29%)
    1 / 154 (0.65%)
    2 / 356 (0.56%)
    0 / 357 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    2 / 357 (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
    Abdominal hernia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Dental cyst
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Dysphagia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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 perforation
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Gastritis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 155 (0.65%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Inguinal hernia strangulated
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Large intestine polyp
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Obstruction gastric
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 155 (0.65%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Biliary colic
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Cholecystitis acute
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Pyoderma gangrenosum
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Nephrolithiasis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Renal colic
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Intervertebral disc displacement
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    1 / 357 (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
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    0 / 357 (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
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 155 (1.29%)
    0 / 154 (0.00%)
    5 / 356 (1.40%)
    1 / 357 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Pyelonephritis acute
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    2 / 357 (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
    Respiratory tract infection
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    1 / 357 (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
    Bronchitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 155 (0.65%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Rhinovirus infection
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Tuberculosis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    0 / 356 (0.00%)
    0 / 357 (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
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    1 / 154 (0.65%)
    0 / 356 (0.00%)
    1 / 357 (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
    Diabetes mellitus
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    Glucose tolerance impaired
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 155 (0.00%)
    0 / 154 (0.00%)
    1 / 356 (0.28%)
    0 / 357 (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
    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
    24 / 45 (53.33%)
    117 / 155 (75.48%)
    118 / 154 (76.62%)
    239 / 356 (67.13%)
    249 / 357 (69.75%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 45 (0.00%)
    13 / 155 (8.39%)
    12 / 154 (7.79%)
    29 / 356 (8.15%)
    39 / 357 (10.92%)
         occurrences all number
    0
    19
    16
    47
    77
    General disorders and administration site conditions
    Injection site pain
         subjects affected / exposed
    3 / 45 (6.67%)
    7 / 155 (4.52%)
    5 / 154 (3.25%)
    13 / 356 (3.65%)
    16 / 357 (4.48%)
         occurrences all number
    11
    44
    21
    144
    92
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 45 (0.00%)
    13 / 155 (8.39%)
    3 / 154 (1.95%)
    18 / 356 (5.06%)
    13 / 357 (3.64%)
         occurrences all number
    0
    13
    3
    22
    14
    Nausea
         subjects affected / exposed
    2 / 45 (4.44%)
    8 / 155 (5.16%)
    1 / 154 (0.65%)
    9 / 356 (2.53%)
    12 / 357 (3.36%)
         occurrences all number
    2
    12
    1
    9
    13
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    14 / 45 (31.11%)
    73 / 155 (47.10%)
    75 / 154 (48.70%)
    148 / 356 (41.57%)
    146 / 357 (40.90%)
         occurrences all number
    23
    177
    211
    412
    376
    Cough
         subjects affected / exposed
    3 / 45 (6.67%)
    8 / 155 (5.16%)
    8 / 154 (5.19%)
    18 / 356 (5.06%)
    21 / 357 (5.88%)
         occurrences all number
    5
    11
    10
    36
    23
    Oropharyngeal pain
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 155 (1.94%)
    8 / 154 (5.19%)
    11 / 356 (3.09%)
    8 / 357 (2.24%)
         occurrences all number
    1
    3
    8
    11
    9
    Rhinitis allergic
         subjects affected / exposed
    1 / 45 (2.22%)
    6 / 155 (3.87%)
    14 / 154 (9.09%)
    9 / 356 (2.53%)
    13 / 357 (3.64%)
         occurrences all number
    2
    7
    17
    11
    17
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 45 (2.22%)
    10 / 155 (6.45%)
    9 / 154 (5.84%)
    20 / 356 (5.62%)
    19 / 357 (5.32%)
         occurrences all number
    1
    12
    10
    22
    21
    Arthralgia
         subjects affected / exposed
    1 / 45 (2.22%)
    11 / 155 (7.10%)
    4 / 154 (2.60%)
    24 / 356 (6.74%)
    17 / 357 (4.76%)
         occurrences all number
    1
    12
    4
    27
    18
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    6 / 45 (13.33%)
    30 / 155 (19.35%)
    41 / 154 (26.62%)
    72 / 356 (20.22%)
    60 / 357 (16.81%)
         occurrences all number
    10
    47
    66
    120
    101
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 45 (13.33%)
    23 / 155 (14.84%)
    28 / 154 (18.18%)
    52 / 356 (14.61%)
    64 / 357 (17.93%)
         occurrences all number
    9
    35
    51
    81
    121
    Bronchitis
         subjects affected / exposed
    4 / 45 (8.89%)
    19 / 155 (12.26%)
    22 / 154 (14.29%)
    44 / 356 (12.36%)
    33 / 357 (9.24%)
         occurrences all number
    5
    26
    30
    63
    47
    Sinusitis
         subjects affected / exposed
    2 / 45 (4.44%)
    13 / 155 (8.39%)
    15 / 154 (9.74%)
    28 / 356 (7.87%)
    20 / 357 (5.60%)
         occurrences all number
    4
    31
    34
    36
    25
    Pharyngitis
         subjects affected / exposed
    2 / 45 (4.44%)
    8 / 155 (5.16%)
    8 / 154 (5.19%)
    21 / 356 (5.90%)
    16 / 357 (4.48%)
         occurrences all number
    2
    8
    12
    25
    20
    Urinary tract infection
         subjects affected / exposed
    1 / 45 (2.22%)
    4 / 155 (2.58%)
    6 / 154 (3.90%)
    18 / 356 (5.06%)
    14 / 357 (3.92%)
         occurrences all number
    1
    5
    6
    27
    19
    Acute sinusitis
         subjects affected / exposed
    0 / 45 (0.00%)
    10 / 155 (6.45%)
    7 / 154 (4.55%)
    14 / 356 (3.93%)
    13 / 357 (3.64%)
         occurrences all number
    0
    14
    16
    23
    16
    Influenza
         subjects affected / exposed
    0 / 45 (0.00%)
    6 / 155 (3.87%)
    9 / 154 (5.84%)
    16 / 356 (4.49%)
    8 / 357 (2.24%)
         occurrences all number
    0
    6
    9
    16
    11
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 45 (0.00%)
    4 / 155 (2.58%)
    5 / 154 (3.25%)
    18 / 356 (5.06%)
    13 / 357 (3.64%)
         occurrences all number
    0
    5
    8
    27
    14

    More information

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    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 add fractional exhaled nitric oxygen (FeNO) as an exploratory objective, 4) To update the biomarker subgroups for analysis to include blood eosinophil count. Biomarker-high subjects will be defined as subjects with baseline periostin ≥ 50 ng/mL or blood eosinophils ≥ 300 cells/μL, and biomarker-low subjects will be defined as subjects with baseline periostin < 50 ng/mL and blood eosinophils < 300 cells/μL, 5) To update the secondary efficacy endpoints and exploratory endpoints, 6) To update the Medical Monitor to reflect the current medical monitors, 6) 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
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    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.

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