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

    Summary
    EudraCT number
    		 2012-000180-25
    Trial protocol
    		 SK   DE   PT   HU   IT   CZ   ES   PL   GB   FR  
    Global end of trial date
    28 Dec 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jun 2017
    First version publication date
    28 Jun 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    WB28183
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01875003
    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
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 61 6878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 61 6878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001053-PIP01-10
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Mar 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Dec 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objectives of this study were: 1) To evaluate the efficacy of lebrikizumab compared with placebo as measured by the rate of asthma exacerbations; 2) To evaluate the safety of lebrikizumab compared with placebo as measured by the rate and severity of adverse events and incidence of anti-therapeutic antibodies (ATA); 3) To evaluate the efficacy and safety of different dose levels of lebrikizumab compared with placebo
    Protection of trial subjects
    The study was conducted in full conformance with the International Conference on Harmonisation (ICH) E6 guidelines for Good Clinical Practice (GCP) and the principles of the “Declaration of Helsinki”, or the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. Approval from the Independent Ethics Committee (IEC)/Institutional Review Board (IRB) was obtained before study start and was documented in a letter to the Investigator specifying the date on which the committee met and granted the approval. The Sponsor also obtained approval from the relevant Competent Authority prior to starting the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Aug 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
    United Kingdom: 4
    Country: Number of subjects enrolled
    Spain: 10
    Country: Number of subjects enrolled
    South Africa: 19
    Country: Number of subjects enrolled
    Portugal: 5
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Israel: 13
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    France: 1
    Country: Number of subjects enrolled
    Brazil: 26
    Country: Number of subjects enrolled
    United States: 51
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Peru: 11
    Country: Number of subjects enrolled
    Mexico: 47
    Country: Number of subjects enrolled
    Colombia: 2
    Country: Number of subjects enrolled
    Argentina: 17
    Country: Number of subjects enrolled
    Ukraine: 31
    Country: Number of subjects enrolled
    Slovakia: 6
    Country: Number of subjects enrolled
    Poland: 61
    Country: Number of subjects enrolled
    Hungary: 31
    Country: Number of subjects enrolled
    Czech Republic: 5
    Worldwide total number of subjects
    346
    EEA total number of subjects
    127
    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)
    346
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 579 participants were screened for the study of which 346 were randomized and received at least one dose of study drug.

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Placebo
    Arm description
    		 Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
    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
    Participants received SC injection of lebrikizumab matching placebo via pre-filled syringe Q4W up to 52 weeks.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received SC injection of lebrikizumab matching placebo via vial Q4W up to 52 weeks.

    Arm title
    		 Lebrikizumab 37.5 mg
    Arm description
    		 Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.
    Arm type
    		 Experimental

    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
    Participants received SC injection of lebrikizumab matching placebo via pre-filled syringe Q4W maximum up to 104 weeks.

    Investigational medicinal product name
    Lebrikizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received SC injection of lebrikizumab at dose level of 37.5 mg via vial Q4W maximum up to 104 weeks.

    Arm title
    		 Lebrikizumab 125 mg
    Arm description
    		 Participants received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lebrikizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received SC injection of lebrikizumab at dose level of 125 mg via pre-filled syringe Q4W maximum up to 104 weeks.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received SC injection of lebrikizumab matching placebo via vial Q4W maximum up to 104 weeks.

    Arm title
    		 Placebo/Lebrikizumab 37.5 mg
    Arm description
    		 Participants in 'Placebo' group who were willing to take part in optional active-treatment extension period and who were randomized to this group received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W from Weeks 52 to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lebrikizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received SC injection of lebrikizumab at dose level of 37.5 mg via vial Q4W from Week 52 to maximum up to Week 104.

    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
    Participants received SC injection of lebrikizumab matching placebo via pre-filled syringe Q4W from Week 52 to maximum up to Week 104.

    Arm title
    		 Placebo/Lebrikizumab 125 mg
    Arm description
    		 Participants in 'Placebo' group who were willing to take part in optional active-treatment extension period and who were randomized to this group received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W from Weeks 52 to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lebrikizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received SC injection of lebrikizumab at dose level of 125 mg via pre-filled syringe Q4W from Week 52 to maximum up to Week 104.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received SC injection of lebrikizumab matching placebo via vial Q4W from Week 52 to maximum up to Week 104.

    Number of subjects in period 1
    		Placebo Lebrikizumab 37.5 mg Lebrikizumab 125 mg Placebo/Lebrikizumab 37.5 mg Placebo/Lebrikizumab 125 mg
    Started
    117
    113
    116
    30
    31
    Completed
    0
    30
    31
    16
    14
    Not completed
    117
    83
    85
    14
    17
         Consent withdrawn by subject
    16
    13
    5
    4
    1
         Physician decision
    -
    2
    1
    -
    -
         Adverse Event
    1
    2
    2
    -
    -
         Pregnancy
    -
    -
    -
    -
    1
         Transferred to Other Arm
    61
    -
    -
    -
    -
         Unspecified
    -
    1
    1
    -
    -
         Study Terminated by Sponsor
    35
    61
    66
    9
    13
         Lost to follow-up
    4
    -
    1
    -
    -
         Missing
    -
    4
    9
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    		 All randomized participants who received at least one dose of study drug.

    Reporting group values
    		 Overall Study Total
    Number of subjects
    		 346
    Age Categorical
    Units: Subjects
    Age Continuous
    Intent-to-treat (ITT) population included all randomized participants who received at least one dose of study drug.
    Units: years
        arithmetic mean (standard deviation)
    		 14.2 ( 1.6 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 151 151
        Male
    		 195 195

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.

    Reporting group title
    Lebrikizumab 37.5 mg
    Reporting group description
    		 Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

    Reporting group title
    Lebrikizumab 125 mg
    Reporting group description
    		 Participants received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

    Reporting group title
    Placebo/Lebrikizumab 37.5 mg
    Reporting group description
    		 Participants in 'Placebo' group who were willing to take part in optional active-treatment extension period and who were randomized to this group received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W from Weeks 52 to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

    Reporting group title
    Placebo/Lebrikizumab 125 mg
    Reporting group description
    		 Participants in 'Placebo' group who were willing to take part in optional active-treatment extension period and who were randomized to this group received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W from Weeks 52 to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

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

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    End point title
    		 Rate of Asthma Exacerbations During 52-Week Placebo Controlled Period [1]
    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 hospitalization. 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 1 dose of IV or IM corticosteroids. Rate of asthma exacerbation = total number of exacerbation events divided by total follow-up time in patient years. Adjusted exacerbation rate estimated from a Poisson regression model was reported. Analysis was performed on ITT population.
    End point type
    Primary
    End point timeframe
    52 Weeks
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis was planned to be carried out in the indicated arms only.
    End point values
    		 Placebo Lebrikizumab 37.5 mg Lebrikizumab 125 mg
    Number of subjects analysed
    117
    113
    116
    Units: events per patient year
        number (not applicable)
    0.43
    0.26
    0.21
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Adjusted exacerbation rates and rate ratios were estimated 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 age group.
    Comparison groups
    Placebo v Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    230
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Adjusted Rate Ratio
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 1.03
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Adjusted exacerbation rates and rate ratios were estimated 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 age group.
    Comparison groups
    Placebo v Lebrikizumab 125 mg
    Number of subjects included in analysis
    233
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Adjusted Rate Ratio
    Point estimate
    0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.28
         upper limit
    		 0.83

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

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    End point title
    		 Percent Change from Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52 [2]
    End point description
    FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. The baseline FEV1 was obtained from the last spirometric analysis performed before the first study treatment administration. The percentage change in pre-bronchodilator FEV1 was defined as the change in FEV1 (in liters) from baseline divided by the FEV1 (in liters) at baseline multiplied by 100. ITT populaton; Here ‘Number of Subjects Analysed’ signifies number of participants evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis was planned to be carried out in the indicated arms only.
    End point values
    		 Placebo Lebrikizumab 37.5 mg Lebrikizumab 125 mg
    Number of subjects analysed
    70
    75
    69
    Units: percent change
        arithmetic mean (standard deviation)
    20.8 ( 32.8 )
    27.1 ( 20.9 )
    24.7 ( 28.4 )
    Statistical analysis title
    		 Statisical Analysis 1
    Statistical analysis description
    Mixed model repeated measures (MMRM) analysis with an unstructured covariance matrix was utilized.
    Comparison groups
    Placebo v Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    Method
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 14
    Variability estimate
    Standard error of the mean
    Dispersion value
    4
    Notes
    [3] - The model used percent change from baseline in pre-bronchodilator FEV1 as the response variable and included terms for treatment, visit, treatment*visit, number of asthma exacerbations within the last 12 months, baseline asthma medications and age group.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    MMRM analysis with an unstructured covariance matrix was utilized.
    Comparison groups
    Placebo v Lebrikizumab 125 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    Method
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 9
    Variability estimate
    Standard error of the mean
    Dispersion value
    4
    Notes
    [4] - The model used percent change from baseline in pre-bronchodilator FEV1 as the response variable and included terms for treatment, visit, treatment*visit, number of asthma exacerbations within the last 12 months, baseline asthma medications and age group

    Secondary: Time to First Asthma Exacerbation

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    End point title
    		 Time to First Asthma Exacerbation [5]
    End point description
    An asthma exacerbation was 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 hospitalization. Treatment with systemic corticosteroids was defined as treatment with oral, IV, or IM corticosteroids for at least 3 days or an emergency department visit with at least 1 dose of IV or IM corticosteroids. Median time to first protocol-defined asthma exacerbation was estimated using Kaplan-Meier analysis. 95% Confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley. ITT population. The data ‘99999 (99999 to 99999)’ in the results signifies that median and corresponding CI could not be calculated due to low number of participants who had an event.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis was planned to be carried out in the indicated arms only.
    End point values
    		 Placebo Lebrikizumab 37.5 mg Lebrikizumab 125 mg
    Number of subjects analysed
    117
    113
    116
    Units: weeks
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Stratified Analysis
    Comparison groups
    Placebo v Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    230
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.22
         upper limit
    		 0.73
    Notes
    [6] - Hazard Ratio (HR) was estimated using Cox regression analysis with the following baseline covariates included as stratification factors: number of asthma exacerbations within the last 12 months, baseline asthma medications and age group.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Stratified Analysis
    Comparison groups
    Placebo v Lebrikizumab 125 mg
    Number of subjects included in analysis
    233
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.21
         upper limit
    		 0.66
    Notes
    [7] - HR was estimated using Cox regression analysis with the following baseline covariates included as stratification factors: number of asthma exacerbations within the last 12 months, baseline asthma medications and age group.

    Secondary: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52

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    End point title
    		 Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52 [8]
    End point description
    Measurement of FeNO (in parts per billion [ppb]) was performed using a hand-held portable NIOX MINO® device, in accordance with guidelines published by the American Thoracic Society (ATS) and described in the pulmonary function testing manual. ITT population. Here ‘Number of Subjects Analysed’ signifies number of participants evaluable for this outcome measure, and ‘n’ signifies number of participants evaluable at specified time point, per arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis was planned to be carried out in the indicated arms only.
    End point values
    		 Placebo Lebrikizumab 37.5 mg Lebrikizumab 125 mg
    Number of subjects analysed
    111
    111
    115
    Units: ppb
    arithmetic mean (standard deviation)
        Baseline (n= 111, 111, 115)
    42.42 ( 35.78 )
    45.5 ( 37.79 )
    48.7 ( 42.7 )
        Change at Week 52 (n= 63, 70, 65)
    7.09 ( 29.45 )
    -21.59 ( 29.69 )
    -33.63 ( 38.64 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    MMRM analysis with an unstructured covariance matrix was utilized. Actual subjects included in analysis (at Week 52) = 133.
    Comparison groups
    Placebo v Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    Method
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -21.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.39
         upper limit
    		 -14.55
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.77
    Notes
    [9] - The model used absolute change from baseline in pre-bronchodilator FeNO as the response variable and included terms for treatment, visit, treatment*visit, baseline FeNO, baseline FeNO*visit, number of asthma exacerbations within the last 12 months, baseline asthma medications and age group.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    MMRM analysis with an unstructured covariance matrix was utilized. Actual subjects included in analysis (at Week 52) = 128.
    Comparison groups
    Placebo v Lebrikizumab 125 mg
    Number of subjects included in analysis
    226
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    Method
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -30.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -37.87
         upper limit
    		 -22.78
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.84
    Notes
    [10] - The model used absolute change from baseline in pre-bronchodilator FeNO as the response variable and included terms for treatment, visit, treatment*visit, baseline FeNO, baseline FeNO*visit, number of asthma exacerbations within the last 12 months, baseline asthma medications and age group.

    Secondary: Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Overall Score at Week 52

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    End point title
    		 Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Overall Score at Week 52 [11]
    End point description
    The Standardized AQLQ+12 was used to assess the participants’ asthma-specific health-related quality of life. The AQLQ+12 had a recall specification of 2 weeks. The AQLQ+12 was a 32-item questionnaire with 4 domains: activity limitations, symptoms, emotional function, and environmental stimuli. Each of the 32 questions were scored on a scale 1-7. The overall AQLQ+12 score is the mean of the responses to each of the 32 questions, and ranges from 1 to 7. A score 7 indicated no impairments due to asthma, and a score of 1 indicated severe impairment. ITT population. Here ‘Number of Subjects Analysed’ signifies number of participants evaluable for this outcome measure, and ‘n’ signifies number of participants evaluable at specified time point, per arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis was planned to be carried out in the indicated arms only.
    End point values
    		 Placebo Lebrikizumab 37.5 mg Lebrikizumab 125 mg
    Number of subjects analysed
    106
    101
    111
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 106, 101, 111)
    4.42 ( 1.09 )
    4.65 ( 1.15 )
    4.22 ( 1.26 )
        Change at Week 52 (n= 63, 64, 69)
    1.16 ( 1.21 )
    0.98 ( 0.98 )
    1.45 ( 1.33 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    MMRM analysis with an unstructured covariance matrix was utilized. Actual subjects included in analysis (at Week 52) = 127.
    Comparison groups
    Placebo v Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    207
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    Method
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.18
         upper limit
    		 0.41
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Notes
    [12] - The model used absolute change from baseline in AQLQ+12 score as the response variable and included terms for treatment, visit, treatment*visit, baseline AQLQ+12, baseline AQLQ+12*visit, number of asthma exacerbations within the last 12 months, baseline asthma medications, and age group.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    MMRM analysis with an unstructured covariance matrix was utilized. Actual subjects included in analysis (at Week 52) = 132.
    Comparison groups
    Placebo v Lebrikizumab 125 mg
    Number of subjects included in analysis
    217
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    Method
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 0.44
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.15
    Notes
    [13] - The model used absolute change from baseline in AQLQ+12 score as the response variable and included terms for treatment, visit, treatment*visit, baseline AQLQ+12, baseline AQLQ+12*visit, number of asthma exacerbations within the last 12 months, baseline asthma medications, and age group.

    Secondary: Change From Baseline in Asthma Rescue Medication Use at Week 52

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    End point title
    		 Change From Baseline in Asthma Rescue Medication Use at Week 52 [14]
    End point description
    Participants were allowed to use short-acting bronchodilators as asthma rescue medication. Baseline asthma rescue medication use was defined as the average number of puffs per day over the 7 days prior to and on the day of randomization. Participants must have recorded their asthma rescue medication use for at least 4 days to have a baseline score calculated. The post-baseline asthma medication use for any timepoint was defined as the average number of puffs per day over the last 28 days on or prior to the timepoint. Participants must have recorded their asthma rescue medication use for at least 14 days during a 28-day interval to have a score calculated for the respective timepoint. For nebulizer use, one treatment (inhalation) was considered equivalent to 4 puffs. ITT population. Here ‘Number of Subjects Analysed’ signifies number of participants evaluable for this outcome measure, and ‘n’ signifies number of participants evaluable at specified time point, per arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    Notes
    [14] - 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: Analysis was planned to be carried out in the indicated arms only.
    End point values
    		 Placebo Lebrikizumab 37.5 mg Lebrikizumab 125 mg
    Number of subjects analysed
    109
    109
    113
    Units: puffs per day
    arithmetic mean (standard deviation)
        Baseline (n= 109, 109, 113)
    2.17 ( 4.09 )
    1.47 ( 1.78 )
    2.23 ( 3.92 )
        Change at Week 52 (n=51, 58, 58)
    -0.79 ( 1.95 )
    -0.56 ( 1.35 )
    -0.81 ( 3.15 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    MMRM analysis with compound symmetry covariance matrix was utilized. Actual subjects included in analysis (at Week 52) = 109.
    Comparison groups
    Placebo v Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    218
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    Method
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.67
         upper limit
    		 0.58
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32
    Notes
    [15] - The model used absolute change from baseline in asthma rescue medication use as the response variable and included terms for treatment, visit, treatment*visit, baseline rescue medication use, baseline rescue medication use*visit, number of asthma exacerbations within the last 12 months, baseline asthma medications, and age group.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    MMRM analysis with compound symmetry covariance matrix was utilized. Actual subjects included in analysis (at Week 52) = 109.
    Comparison groups
    Placebo v Lebrikizumab 125 mg
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [16]
    Method
    Parameter type
    		 Difference in Adjusted Means
    Point estimate
    0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.48
         upper limit
    		 0.77
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.32
    Notes
    [16] - The model used absolute change from baseline in asthma rescue medication use as the response variable and included terms for treatment, visit, treatment*visit, baseline rescue medication use, baseline rescue medication use*visit, number of asthma exacerbations within the last 12 months, baseline asthma medications, and age group.

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

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    End point title
    		 Rate of Urgent Asthma-Related Health Care Utilization (HCU) Events [17]
    End point description
    Urgent asthma-related HCU events included hospitalizations, emergency department visits, and acute care visits. Rate of urgent asthma-related HCU events = total number of urgent asthma-related HCU events divided by total follow-up time in patient years. ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 52
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis was planned to be carried out in the indicated arms only.
    End point values
    		 Placebo Lebrikizumab 37.5 mg Lebrikizumab 125 mg
    Number of subjects analysed
    117
    113
    116
    Units: events per patient year
        number (not applicable)
    0.18
    0.07
    0.06
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Adjusted health care utilization rates and rate ratios were 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 age group.
    Comparison groups
    Placebo v Lebrikizumab 37.5 mg
    Number of subjects included in analysis
    230
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Ratio of Adjusted HCU Rate
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.16
         upper limit
    		 1
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Adjusted health care utilization rates and rate ratios were 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 age group.
    Comparison groups
    Placebo v Lebrikizumab 125 mg
    Number of subjects included in analysis
    233
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Ratio of Adjusted HCU Rate
    Point estimate
    0.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1
         upper limit
    		 0.72

    Secondary: Injection Acceptability Questionnaire (IAQ) Score

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    End point title
    		 Injection Acceptability Questionnaire (IAQ) Score [18]
    End point description
    The acceptability of the injections of study drug was addressed by measuring the level of pain that participants experienced. Participants assessed pain associated with study drug administration using the IAQ within 10 minutes of study drug administration. The IAQ score ranged from 0 to 10; where 0 = no pain and 10 = worst pain imaginable. ITT population. Here ‘Number of Subjects Analysed’ signifies number of participants evaluable for this outcome measure, and ‘n’ signifies number of participants evaluable at specified time point, per arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
    Notes
    [18] - 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: Analysis was planned to be carried out in the indicated arms only.
    End point values
    		 Placebo Lebrikizumab 37.5 mg Lebrikizumab 125 mg
    Number of subjects analysed
    107
    100
    105
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n= 107, 100, 105)
    3.5 ( 2.6 )
    3.5 ( 2.3 )
    3.9 ( 2.6 )
        Week 4 (n= 101, 102, 105)
    3.7 ( 2.7 )
    4.1 ( 2.6 )
    3.9 ( 2.7 )
        Week 8 (n= 91, 95, 102)
    3.7 ( 2.5 )
    3.7 ( 2.4 )
    3.5 ( 2.4 )
        Week 12 (n= 92, 92, 96)
    3.4 ( 2.4 )
    3.4 ( 2.7 )
    3.5 ( 2.5 )
        Week 16 (n= 87, 88, 95)
    3.2 ( 2.5 )
    3.2 ( 2.6 )
    3.3 ( 2.5 )
        Week 20 (n= 84, 84, 87)
    3.1 ( 2.4 )
    3 ( 2.6 )
    3.1 ( 2.4 )
        Week 24 (n= 80, 82, 85)
    3.3 ( 2.3 )
    3.1 ( 2.5 )
    3.3 ( 2.1 )
        Week 28 (n= 82, 81, 84)
    2.9 ( 2.2 )
    2.8 ( 2.4 )
    2.8 ( 2.2 )
        Week 32 (n= 83, 79, 80)
    2.9 ( 2.2 )
    2.9 ( 2.7 )
    3 ( 2.1 )
        Week 36 (n= 77, 73, 80)
    3.1 ( 2.3 )
    3.1 ( 2.7 )
    3.1 ( 2.1 )
        Week 40 (n= 70, 69, 74)
    3 ( 2.3 )
    3 ( 2.4 )
    2.7 ( 2.1 )
        Week 44 (n= 58, 65, 73)
    2.9 ( 2.1 )
    2.9 ( 2.2 )
    3.2 ( 2.4 )
        Week 48 (n= 58, 60, 67)
    2.9 ( 2.3 )
    2.9 ( 2.6 )
    2.7 ( 2.2 )
    No statistical analyses for this end point

    Secondary: Minimum Observed Serum Concentration (Ctrough) for Lebrikizumab

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    End point title
    		 Minimum Observed Serum Concentration (Ctrough) for Lebrikizumab [19]
    End point description
    Participants who received at least one dose of lebrikizumab and had at least one post-baseline evaluable sample were included in the analysis. Results of post-dose samples which were less than reportable were set to 0.045 micrograms per milliliter (mcg/mL) that is half of minimum quantifiable concentration value (0.09 mcg/mL). Here ‘Number of Subjects Analysed’ signifies number of participants evaluable for this outcome measure, and ‘n’ signifies number of participants evaluable at specified time point, per arm, respectively. The data ‘99999’ in the results signifies that data was not available because no participant was evaluable at indicated time point, and data '9999' signifies that data was not reported because more that one-third values were less than reportable.
    End point type
    Secondary
    End point timeframe
    Predose (Hour 0) at Weeks 4, 12, 24, 36, and 52
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Analysis was planned to be carried out in the indicated arms only.
    End point values
    		 Lebrikizumab 37.5 mg Lebrikizumab 125 mg
    Number of subjects analysed
    47
    50
    Units: mcg/mL
    arithmetic mean (standard deviation)
        Week 4 (n= 47, 50)
    3.25 ( 1.58 )
    12.2 ( 5.28 )
        Week 12 (n=42, 40)
    5.72 ( 2.81 )
    21.7 ( 9.37 )
        Week 24 (n= 28, 29)
    7.15 ( 6.23 )
    25.7 ( 9.84 )
        Week 36 (n= 18, 23)
    3.88 ( 2.92 )
    23.9 ( 9.87 )
        Week 52 (4, 0)
    9999 ( 9999 )
    99999 ( 99999 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 24 weeks after last dose of study treatment (overall 128 weeks)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received SC injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) Q4W for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.

    Reporting group title
    Lebrikizumab 37.5 mg
    Reporting group description
    		 Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

    Reporting group title
    Lebrikizumab 125 mg
    Reporting group description
    		 Participants received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

    Reporting group title
    Placebo/ Lebrikizumab 37.5 mg
    Reporting group description
    		 Participants in 'Placebo' group who were willing to take part in optional active-treatment extension period and who were randomized to this group received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W from Weeks 52 to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

    Reporting group title
    Placebo/ Lebrikizumab 125 mg
    Reporting group description
    		 Participants in 'Placebo' group who were willing to take part in optional active-treatment extension period and who were randomized to this group received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W from Weeks 52 to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

    Serious adverse events
    		 Placebo Lebrikizumab 37.5 mg Lebrikizumab 125 mg Placebo/ Lebrikizumab 37.5 mg Placebo/ Lebrikizumab 125 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 56 (5.36%)
    6 / 113 (5.31%)
    8 / 116 (6.90%)
    3 / 30 (10.00%)
    4 / 31 (12.90%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    1 / 116 (0.86%)
    0 / 30 (0.00%)
    0 / 31 (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
    Headache
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    0 / 116 (0.00%)
    1 / 30 (3.33%)
    0 / 31 (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 / 56 (0.00%)
    0 / 113 (0.00%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    1 / 31 (3.23%)
         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
    Blood and lymphatic system disorders
    Eosinophilia
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (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
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    1 / 116 (0.86%)
    0 / 30 (0.00%)
    0 / 31 (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
    Anaphylactic shock
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    1 / 116 (0.86%)
    0 / 30 (0.00%)
    0 / 31 (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
    Abdominal pain
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    1 / 31 (3.23%)
         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
    Diarrhoea
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 113 (0.00%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (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
    Vomiting
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 113 (0.00%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (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
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 56 (1.79%)
    2 / 113 (1.77%)
    2 / 116 (1.72%)
    1 / 30 (3.33%)
    2 / 31 (6.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthmatic crisis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (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
    Dyspnoea
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 113 (0.00%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (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
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (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
    Urticaria
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (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
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    1 / 116 (0.86%)
    0 / 30 (0.00%)
    0 / 31 (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
    Appendicitis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    1 / 116 (0.86%)
    0 / 30 (0.00%)
    0 / 31 (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
    Infection
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (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
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    1 / 116 (0.86%)
    0 / 30 (0.00%)
    0 / 31 (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
    Sinusitis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    0 / 116 (0.00%)
    1 / 30 (3.33%)
    0 / 31 (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
    Viral infection
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 113 (0.00%)
    1 / 116 (0.86%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic syndrome
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    1 / 116 (0.86%)
    0 / 30 (0.00%)
    0 / 31 (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
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 113 (0.00%)
    0 / 116 (0.00%)
    1 / 30 (3.33%)
    0 / 31 (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 Lebrikizumab 37.5 mg Lebrikizumab 125 mg Placebo/ Lebrikizumab 37.5 mg Placebo/ Lebrikizumab 125 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    23 / 56 (41.07%)
    67 / 113 (59.29%)
    72 / 116 (62.07%)
    23 / 30 (76.67%)
    24 / 31 (77.42%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 56 (1.79%)
    2 / 113 (1.77%)
    3 / 116 (2.59%)
    2 / 30 (6.67%)
    0 / 31 (0.00%)
         occurrences all number
    2
    2
    3
    2
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 56 (1.79%)
    3 / 113 (2.65%)
    0 / 116 (0.00%)
    0 / 30 (0.00%)
    2 / 31 (6.45%)
         occurrences all number
    1
    3
    0
    0
    2
    Headache
         subjects affected / exposed
    2 / 56 (3.57%)
    8 / 113 (7.08%)
    11 / 116 (9.48%)
    3 / 30 (10.00%)
    6 / 31 (19.35%)
         occurrences all number
    2
    20
    22
    6
    7
    General disorders and administration site conditions
    Injection site extravasation
         subjects affected / exposed
    0 / 56 (0.00%)
    2 / 113 (1.77%)
    2 / 116 (1.72%)
    1 / 30 (3.33%)
    2 / 31 (6.45%)
         occurrences all number
    0
    8
    12
    4
    2
    Injection site induration
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    3 / 116 (2.59%)
    1 / 30 (3.33%)
    2 / 31 (6.45%)
         occurrences all number
    0
    1
    3
    1
    3
    Injection site pain
         subjects affected / exposed
    0 / 56 (0.00%)
    2 / 113 (1.77%)
    2 / 116 (1.72%)
    2 / 30 (6.67%)
    1 / 31 (3.23%)
         occurrences all number
    0
    4
    2
    38
    1
    Eye disorders
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    0 / 116 (0.00%)
    2 / 30 (6.67%)
    0 / 31 (0.00%)
         occurrences all number
    0
    3
    0
    2
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    6 / 116 (5.17%)
    1 / 30 (3.33%)
    0 / 31 (0.00%)
         occurrences all number
    0
    3
    6
    1
    0
    Diarrhoea
         subjects affected / exposed
    1 / 56 (1.79%)
    2 / 113 (1.77%)
    2 / 116 (1.72%)
    2 / 30 (6.67%)
    1 / 31 (3.23%)
         occurrences all number
    1
    2
    2
    2
    1
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    12 / 56 (21.43%)
    25 / 113 (22.12%)
    31 / 116 (26.72%)
    11 / 30 (36.67%)
    15 / 31 (48.39%)
         occurrences all number
    21
    53
    58
    20
    43
    Cough
         subjects affected / exposed
    1 / 56 (1.79%)
    6 / 113 (5.31%)
    3 / 116 (2.59%)
    2 / 30 (6.67%)
    1 / 31 (3.23%)
         occurrences all number
    1
    8
    3
    2
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 56 (0.00%)
    7 / 113 (6.19%)
    0 / 116 (0.00%)
    1 / 30 (3.33%)
    2 / 31 (6.45%)
         occurrences all number
    0
    10
    0
    1
    2
    Rhinitis allergic
         subjects affected / exposed
    1 / 56 (1.79%)
    3 / 113 (2.65%)
    6 / 116 (5.17%)
    2 / 30 (6.67%)
    2 / 31 (6.45%)
         occurrences all number
    2
    4
    8
    6
    5
    Wheezing
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    0 / 116 (0.00%)
    1 / 30 (3.33%)
    2 / 31 (6.45%)
         occurrences all number
    0
    1
    0
    2
    2
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    1 / 116 (0.86%)
    2 / 30 (6.67%)
    1 / 31 (3.23%)
         occurrences all number
    0
    1
    1
    2
    1
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    0 / 56 (0.00%)
    2 / 113 (1.77%)
    3 / 116 (2.59%)
    1 / 30 (3.33%)
    3 / 31 (9.68%)
         occurrences all number
    0
    2
    4
    1
    6
    Bronchitis
         subjects affected / exposed
    2 / 56 (3.57%)
    10 / 113 (8.85%)
    6 / 116 (5.17%)
    4 / 30 (13.33%)
    4 / 31 (12.90%)
         occurrences all number
    2
    12
    7
    7
    7
    Gastroenteritis
         subjects affected / exposed
    1 / 56 (1.79%)
    3 / 113 (2.65%)
    3 / 116 (2.59%)
    3 / 30 (10.00%)
    1 / 31 (3.23%)
         occurrences all number
    1
    3
    3
    3
    1
    Influenza
         subjects affected / exposed
    0 / 56 (0.00%)
    5 / 113 (4.42%)
    6 / 116 (5.17%)
    1 / 30 (3.33%)
    1 / 31 (3.23%)
         occurrences all number
    0
    5
    9
    1
    1
    Laryngitis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    1 / 116 (0.86%)
    0 / 30 (0.00%)
    2 / 31 (6.45%)
         occurrences all number
    0
    1
    1
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    4 / 56 (7.14%)
    14 / 113 (12.39%)
    13 / 116 (11.21%)
    6 / 30 (20.00%)
    7 / 31 (22.58%)
         occurrences all number
    5
    31
    18
    11
    10
    Pharyngitis
         subjects affected / exposed
    5 / 56 (8.93%)
    10 / 113 (8.85%)
    18 / 116 (15.52%)
    8 / 30 (26.67%)
    4 / 31 (12.90%)
         occurrences all number
    5
    14
    28
    11
    7
    Respiratory tract infection
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    5 / 116 (4.31%)
    2 / 30 (6.67%)
    2 / 31 (6.45%)
         occurrences all number
    0
    1
    5
    4
    4
    Rhinitis
         subjects affected / exposed
    1 / 56 (1.79%)
    5 / 113 (4.42%)
    6 / 116 (5.17%)
    3 / 30 (10.00%)
    3 / 31 (9.68%)
         occurrences all number
    1
    5
    6
    7
    3
    Sinusitis
         subjects affected / exposed
    4 / 56 (7.14%)
    2 / 113 (1.77%)
    3 / 116 (2.59%)
    1 / 30 (3.33%)
    1 / 31 (3.23%)
         occurrences all number
    4
    3
    4
    1
    2
    Tonsillitis
         subjects affected / exposed
    2 / 56 (3.57%)
    9 / 113 (7.96%)
    8 / 116 (6.90%)
    2 / 30 (6.67%)
    3 / 31 (9.68%)
         occurrences all number
    2
    9
    11
    3
    3
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 56 (5.36%)
    16 / 113 (14.16%)
    11 / 116 (9.48%)
    2 / 30 (6.67%)
    2 / 31 (6.45%)
         occurrences all number
    3
    22
    14
    2
    6
    Viral infection
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    3 / 116 (2.59%)
    0 / 30 (0.00%)
    2 / 31 (6.45%)
         occurrences all number
    0
    1
    3
    0
    4
    Viral pharyngitis
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 113 (0.88%)
    1 / 116 (0.86%)
    0 / 30 (0.00%)
    2 / 31 (6.45%)
         occurrences all number
    0
    1
    1
    0
    2
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 56 (0.00%)
    2 / 113 (1.77%)
    2 / 116 (1.72%)
    1 / 30 (3.33%)
    3 / 31 (9.68%)
         occurrences all number
    0
    2
    4
    1
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Mar 2015
    Active treatment extension was converted to optional; Timing of biomarker-related blood draws was changed to reduce required number of blood draws; The frequency of certain study assessments was reduced, including blood draws, spirometry, FeNO, urinalysis, and patient-reported outcomes; The Week 16 visit during the safety follow-up period was eliminated.

    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.
    The enrollment was closed, and dosing was terminated in this study following the sponsor’s decision to discontinue development of lebrikizumab. Thus, this study was treated as exploratory (rather than confirmatory).
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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