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    Clinical Trial Results:
    A Multicenter, Randomized, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab 100 mg in Patients with Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) with a History of Frequent COPD Exacerbations and Elevated Peripheral Blood Eosinophils.

    Summary
    EudraCT number
    		 2019-001800-39
    Trial protocol
    		 DK   PL   HU   CZ   DE   AT   ES   GB   NL   BE   GR   IT  
    Global end of trial date
    28 Jul 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Aug 2026
    First version publication date
    13 Aug 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D3251C00014
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    151 85, Sodertalje, Sweden,
    Public contact
    Global Clinical Lead, AstraZeneca, 1 877-240-9479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, 1 877-240-9479, information.center@astrazeneca.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
    05 Sep 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Jul 2025
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Jul 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effect of benralizumab 100 mg on COPD exacerbations in patients with moderate to very severe COPD
    Protection of trial subjects
    Participants were maintained on triple (ICS/LABA/LAMA) background therapy, from enrolment throughout the run-in and treatment periods. Background inhaled medications may be provided/reimbursed by AstraZeneca (also referred to as ‘AZ’ or sponsor), based on local regulations on participant participation in research studies and medication access.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    26 Aug 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 55
    Country: Number of subjects enrolled
    United Kingdom: 30
    Country: Number of subjects enrolled
    Greece: 25
    Country: Number of subjects enrolled
    Spain: 25
    Country: Number of subjects enrolled
    Türkiye: 21
    Country: Number of subjects enrolled
    Denmark: 19
    Country: Number of subjects enrolled
    Austria: 18
    Country: Number of subjects enrolled
    Italy: 17
    Country: Number of subjects enrolled
    Sweden: 5
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Argentina: 48
    Country: Number of subjects enrolled
    Brazil: 34
    Country: Number of subjects enrolled
    Colombia: 23
    Country: Number of subjects enrolled
    Chile: 17
    Country: Number of subjects enrolled
    New Zealand: 15
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    China: 59
    Country: Number of subjects enrolled
    Korea, Republic of: 23
    Country: Number of subjects enrolled
    Japan: 22
    Country: Number of subjects enrolled
    Viet Nam: 13
    Country: Number of subjects enrolled
    Philippines: 9
    Country: Number of subjects enrolled
    India: 8
    Country: Number of subjects enrolled
    United States: 68
    Country: Number of subjects enrolled
    Canada: 15
    Country: Number of subjects enrolled
    Mexico: 8
    Country: Number of subjects enrolled
    Hungary: 39
    Country: Number of subjects enrolled
    Poland: 23
    Country: Number of subjects enrolled
    Czechia: 13
    Country: Number of subjects enrolled
    Bulgaria: 11
    Worldwide total number of subjects
    676
    EEA total number of subjects
    256
    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)
    258
    From 65 to 84 years
    416
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 2,026 participants were enrolled.

    Pre-assignment
    Screening details
    		 1,337 participants are not randomized due to screen failure or other reasons. The rest 689 participants were randomized. 13 of which were removed from analyses due to GCP non-compliance before study unblinding. Remaining 676 participants, benralizumab arm (331 participants) or placebo arm (345 participants), were included in the analysis.

    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, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Benralizumab 100 mg
    Arm description
    		 Administered by subcutaneous (SC) injection every 4 weeks for the first 3 doses and then every 8 weeks thereafter (Q8W)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Benralizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Benralizumab 100 mg every 4 weeks for the first 3 doses and then every 8 weeks thereafter (Q8W)

    Arm title
    		 Placebo
    Arm description
    		 Administered by SC injection every 4 weeks for the first 3 doses and then Q8W
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Matching placebo every 4 weeks for the first 3 doses and then every 8 weeks thereafter (Q8W)

    Number of subjects in period 1
    		Benralizumab 100 mg Placebo
    Started
    331
    345
    Completed
    226
    218
    Not completed
    105
    127
         Adverse event, serious fatal
    28
    33
         Consent withdrawn by subject
    58
    65
         Physician decision
    5
    4
         Adverse event, non-fatal
    4
    10
         Other reasons
    9
    14
         Lost to follow-up
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Benralizumab 100 mg
    Reporting group description
    		 Administered by subcutaneous (SC) injection every 4 weeks for the first 3 doses and then every 8 weeks thereafter (Q8W)

    Reporting group title
    Placebo
    Reporting group description
    		 Administered by SC injection every 4 weeks for the first 3 doses and then Q8W

    Reporting group values
    		 Benralizumab 100 mg Placebo Total
    Number of subjects
    		 331 345 676
    Age Categorical
    Units: Participants
        Between 18 and 65 years
    		 122 136 258
        >=65 years
    		 209 209 418
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 67.0 ( 7.72 ) 66.8 ( 7.28 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 101 111 212
        Male
    		 230 234 464
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 61 62 123
        Not Hispanic or Latino
    		 270 283 553
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 244 250 494
        Black or African American
    		 1 4 5
        Asian
    		 66 72 138
        Other
    		 20 19 39

    End points

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    End points reporting groups
    Reporting group title
    Benralizumab 100 mg
    Reporting group description
    		 Administered by subcutaneous (SC) injection every 4 weeks for the first 3 doses and then every 8 weeks thereafter (Q8W)

    Reporting group title
    Placebo
    Reporting group description
    		 Administered by SC injection every 4 weeks for the first 3 doses and then Q8W

    Primary: Annualized rate of moderate or severe COPD exacerbations of participants with >=3 exacerbations in the previous year.

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    End point title
    		 Annualized rate of moderate or severe COPD exacerbations of participants with >=3 exacerbations in the previous year.
    End point description
    Moderate or severe COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; and/or Use of antibiotics; and/or An inpatient hospitalization or death due to COPD. Annualized Exacerbation Rate = 365.25*Total Number of Exacerbations / Total time at risk within the treatment group (days)
    End point type
    Primary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    241
    249
    Units: Annualized exacerbation rate
        least squares mean (confidence interval 95%)
    2.04 (1.69 to 2.46)
    2.46 (2.05 to 2.95)
    Statistical analysis title
    		 Negative binomial model
    Statistical analysis description
    Null hypothesis: Rate ratio (benralizumab vs Placebo) = 1
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1172
    Method
    		 Negative binomial model
    Parameter type
    		 Rate ratio
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 1.05

    Primary: Annualized rate of moderate or severe COPD exacerbations of participants with >=2 exacerbations in the previous year

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    End point title
    		 Annualized rate of moderate or severe COPD exacerbations of participants with >=2 exacerbations in the previous year
    End point description
    Moderate or severe COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; and/or Use of antibiotics; and/or An inpatient hospitalization or death due to COPD. Annualized Exacerbation Rate = 365.25*Total Number of Exacerbations / Total time at risk within the treatment group (days)
    End point type
    Primary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    331
    345
    Units: Annualized exacerbation rate
        least squares mean (confidence interval 95%)
    1.86 (1.58 to 2.20)
    2.05 (1.75 to 2.41)
    Statistical analysis title
    		 Negative binomial model
    Statistical analysis description
    Null hypothesis: Rate ratio (benralizumab vs Placebo) = 1
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3367
    Method
    		 Negative binomial model
    Parameter type
    		 Rate ratio
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.11

    Secondary: Key secondary endpoint: Annualized rate of severe COPD exacerbations of participants with >=3 exacerbations in the previous year

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    End point title
    		 Key secondary endpoint: Annualized rate of severe COPD exacerbations of participants with >=3 exacerbations in the previous year
    End point description
    Severe COPD exacerbation is defined by symptomatic worsening of COPD requiring an inpatient hospitalization or results in death due to COPD. Annualized Exacerbation Rate = 365.25*Total Number of Exacerbations / Total time at risk within the treatment group (days)
    End point type
    Secondary
    End point timeframe
    Through end of treatment
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    241
    249
    Units: Annualized exacerbation rate
        least squares mean (confidence interval 95%)
    0.37 (0.28 to 0.49)
    0.39 (0.30 to 0.52)
    Statistical analysis title
    		 Negative binomial model
    Statistical analysis description
    Null hypothesis: Rate ratio (benralizumab vs Placebo) = 1
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7644
    Method
    		 Negative binomial model
    Parameter type
    		 Rate ratio
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 1.35

    Secondary: Key secondary endpoint: Annualized rate of severe COPD exacerbations of participants with >=2 exacerbations in the previous year

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    End point title
    		 Key secondary endpoint: Annualized rate of severe COPD exacerbations of participants with >=2 exacerbations in the previous year
    End point description
    Severe COPD exacerbation is defined by symptomatic worsening of COPD requiring an inpatient hospitalization or results in death due to COPD. Annualized Exacerbation Rate = 365.25*Total Number of Exacerbations / Total time at risk within the treatment group (days)
    End point type
    Secondary
    End point timeframe
    Through end of treatment
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    331
    345
    Units: Annualized exacerbation rate
        least squares mean (confidence interval 95%)
    0.37 (0.30 to 0.47)
    0.33 (0.26 to 0.42)
    Statistical analysis title
    		 Negative binomial model
    Statistical analysis description
    Null hypothesis: Rate ratio (benralizumab vs Placebo) = 1
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.4328
    Method
    		 Negative binomial model
    Parameter type
    		 Rate ratio
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.53

    Secondary: Key secondary endpoint: Change from baseline in SGRQ total and domain scores at Week 56 of participants with >=3 exacerbations in the previous year

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    End point title
    		 Key secondary endpoint: Change from baseline in SGRQ total and domain scores at Week 56 of participants with >=3 exacerbations in the previous year
    End point description
    The St. George’s Respiratory Questionnaire (SGRQ) is a 50-item PRO instrument developed to measure the health status of patients with airway obstruction diseases. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; and part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual’s respiratory condition. The SGRQ yields a total score and 3 domain scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. Likewise, the domain scores range from 0 to 100, with higher scores indicative of greater impairment.
    End point type
    Secondary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    241
    249
    Units: Score
    arithmetic mean (standard deviation)
        Total Score
    -7.06 ( 16.804 )
    -4.95 ( 16.915 )
        Symptoms
    -7.16 ( 18.495 )
    -5.46 ( 16.822 )
        Activity
    -8.34 ( 19.958 )
    -6.81 ( 18.663 )
        Impacts
    -6.37 ( 20.335 )
    -3.75 ( 21.387 )
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in SGRQ total score at Week 56 (tezepelumab minus placebo) = 0
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1686
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -2.092
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.072
         upper limit
    		 0.889

    Secondary: Key secondary endpoint: Change from baseline in SGRQ total and domain scores at Week 56 of participants with >=2 exacerbations in the previous year

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    End point title
    		 Key secondary endpoint: Change from baseline in SGRQ total and domain scores at Week 56 of participants with >=2 exacerbations in the previous year
    End point description
    The St. George’s Respiratory Questionnaire (SGRQ) is a 50-item PRO instrument developed to measure the health status of patients with airway obstruction diseases. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; and part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual’s respiratory condition. The SGRQ yields a total score and 3 domain scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. Likewise, the domain scores range from 0 to 100, with higher scores indicative of greater impairment.
    End point type
    Secondary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    331
    345
    Units: Score
    arithmetic mean (standard deviation)
        Total Score
    -5.80 ( 16.185 )
    -3.89 ( 16.141 )
        Symptoms
    -6.10 ( 18.104 )
    -4.97 ( 16.768 )
        Activity
    -6.81 ( 19.381 )
    -4.96 ( 17.618 )
        Impacts
    -5.20 ( 19.685 )
    -2.95 ( 20.592 )
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in SGRQ total score at Week 56 (tezepelumab minus placebo) = 0
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1013
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -2.014
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.424
         upper limit
    		 0.396

    Secondary: Key secondary endpoint: Change from baseline in pre-bronchodilator FEV1 (mL) at Week 56 of participants with >=3 exacerbations in the previous year

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    End point title
    		 Key secondary endpoint: Change from baseline in pre-bronchodilator FEV1 (mL) at Week 56 of participants with >=3 exacerbations in the previous year
    End point description
    Pre-bronchodilator forced expiratory volume in 1 second (FEV1) is defined as the volume of air exhaled from the lungs in the first second of forced expiration.
    End point type
    Secondary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    241
    249
    Units: mL
        arithmetic mean (standard error)
    10.8 ( 268.48 )
    17.3 ( 285.39 )
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in pre-bronchodilator FEV1 at 56 weeks (Benralizumab minus placebo) = 0
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9729
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.882
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -50.081
         upper limit
    		 51.844

    Secondary: Key secondary endpoint: Change from baseline in pre-bronchodilator FEV1 (mL) at Week 56 of participants with >=2 exacerbations in the previous year

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    End point title
    		 Key secondary endpoint: Change from baseline in pre-bronchodilator FEV1 (mL) at Week 56 of participants with >=2 exacerbations in the previous year
    End point description
    Pre-bronchodilator forced expiratory volume in 1 second (FEV1) is defined as the volume of air exhaled from the lungs in the first second of forced expiration.
    End point type
    Secondary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    331
    345
    Units: mL
        arithmetic mean (standard error)
    18.3 ( 252.20 )
    3.8 ( 259.60 )
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in pre-bronchodilator FEV1 at 56 weeks (Benralizumab minus placebo) = 0
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2816
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    21.965
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.062
         upper limit
    		 61.992

    Secondary: Annualized rate of COPD exacerbations that are associated with an emergency room/emergency department visit or a hospitalization due to COPD of participants with >=3 exacerbations in the previous year

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    End point title
    		 Annualized rate of COPD exacerbations that are associated with an emergency room/emergency department visit or a hospitalization due to COPD of participants with >=3 exacerbations in the previous year
    End point description
    The annualized rate of COPD exacerbations that are associated with an emergency room/emergency department (ER) or a hospitalization due to COPD through EOT are calculated similarly to the primary efficacy endpoint. The emergence room/emergence department (ER) and hospitalization due to COPD exacerbation are collected in COPDEX eCRF. Annualized Exacerbation Rate = 365.25*Total Number of Exacerbations / Total time at risk within the treatment group (days)
    End point type
    Secondary
    End point timeframe
    Through end of treatment
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    241
    249
    Units: Annualized exacerbation rate
        least squares mean (confidence interval 95%)
    0.50 (0.39 to 0.64)
    0.60 (0.47 to 0.76)
    Statistical analysis title
    		 Negative binomial model
    Statistical analysis description
    Null hypothesis: Rate ratio (benralizumab vs Placebo) = 1
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2589
    Method
    		 Negative binomial model
    Parameter type
    		 Rate ratio
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 1.14

    Secondary: Annualized rate of COPD exacerbations that are associated with an emergency room/emergency department visit or a hospitalization due to COPD of participants with >=2 exacerbations in the previous year

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    End point title
    		 Annualized rate of COPD exacerbations that are associated with an emergency room/emergency department visit or a hospitalization due to COPD of participants with >=2 exacerbations in the previous year
    End point description
    The annualized rate of COPD exacerbations that are associated with an emergency room/emergency department (ER) or a hospitalization due to COPD through EOT are calculated similarly to the primary efficacy endpoint. The emergence room/emergence department (ER) and hospitalization due to COPD exacerbation are collected in COPDEX eCRF. Annualized Exacerbation Rate = 365.25*Total Number of Exacerbations / Total time at risk within the treatment group (days)
    End point type
    Secondary
    End point timeframe
    Through end of treatment
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    331
    345
    Units: Annualized exacerbation rate
        least squares mean (confidence interval 95%)
    0.48 (0.39 to 0.59)
    0.50 (0.41 to 0.61)
    Statistical analysis title
    		 Negative binomial model
    Statistical analysis description
    Null hypothesis: Rate ratio (benralizumab vs Placebo) = 1
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7971
    Method
    		 Negative binomial model
    Parameter type
    		 Rate ratio
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.26

    Secondary: Time from randomization to the first moderate or severe COPD exacerbation up to Week 56 of participants with >=3 exacerbations in the previous year

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    End point title
    		 Time from randomization to the first moderate or severe COPD exacerbation up to Week 56 of participants with >=3 exacerbations in the previous year
    End point description
    Time from randomization to the first moderate or severe COPD exacerbation = Start Date of first COPD exacerbation − Date of Randomization + 1. The time to first moderate or severe COPD exacerbation for patients who did experience a moderate or severe COPD exacerbation up to Week 56 were censored at Week 56, and for patients who discontinue or are lost-to-follow-up prior to Week 56, at the last time point after which an exacerbation could not be assessed.
    End point type
    Secondary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    241
    249
    Units: Weeks
        median (confidence interval 95%)
    31.7 (24.1 to 40.4)
    26.1 (21.1 to 31.1)
    Statistical analysis title
    		 Proportional hazards regression model
    Statistical analysis description
    Null hypothesis: Hazard ratio (benralizumab vs Placebo) = 1
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1331
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 1.03

    Secondary: Time from randomization to the first moderate or severe COPD exacerbation up to Week 56 of participants with >=2 exacerbations in the previous year

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    End point title
    		 Time from randomization to the first moderate or severe COPD exacerbation up to Week 56 of participants with >=2 exacerbations in the previous year
    End point description
    Time from randomization to the first moderate or severe COPD exacerbation = Start Date of first COPD exacerbation − Date of Randomization + 1. The time to first moderate or severe COPD exacerbation for patients who did experience a moderate or severe COPD exacerbation up to Week 56 were censored at Week 56, and for patients who discontinue or are lost-to-follow-up prior to Week 56, at the last time point after which an exacerbation could not be assessed.
    End point type
    Secondary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    331
    345
    Units: Weeks
        median (confidence interval 95%)
    33.0 (26.6 to 44.1)
    29.1 (25.6 to 33.0)
    Statistical analysis title
    		 Proportional hazards regression model
    Statistical analysis description
    Null hypothesis: Hazard ratio (benralizumab vs Placebo) = 1
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2465
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 1.06

    Secondary: Time from randomization to the first severe COPD exacerbation of participants with >=3 exacerbations in the previous year

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    End point title
    		 Time from randomization to the first severe COPD exacerbation of participants with >=3 exacerbations in the previous year
    End point description
    Time from randomization to the first severe COPD exacerbation = Start Date of first COPD exacerbation − Date of Randomization + 1. The time to first severe COPD exacerbation for patients who did experience a severe COPD exacerbation through EOT were censored at EOT, and for patients who discontinue or are lost-to-follow-up prior to EOT, at the last time point after which an exacerbation could not be assessed.
    End point type
    Secondary
    End point timeframe
    through end of treatment
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    241
    249
    Units: Weeks
        median (confidence interval 95%)
    255.0 (157.1 to 9999)
    194.6 (124.1 to 9999)
    Statistical analysis title
    		 Proportional hazards regression model
    Statistical analysis description
    Null hypothesis: Hazard ratio (benralizumab vs Placebo) = 1
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3566
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.19

    Secondary: Time from randomization to the first severe COPD exacerbation of participants with >=2 exacerbations in the previous year

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    End point title
    		 Time from randomization to the first severe COPD exacerbation of participants with >=2 exacerbations in the previous year
    End point description
    Time from randomization to the first severe COPD exacerbation = Start Date of first COPD exacerbation − Date of Randomization + 1. The time to first severe COPD exacerbation for patients who did experience a severe COPD exacerbation through EOT were censored at EOT, and for patients who discontinue or are lost-to-follow-up prior to EOT, at the last time point after which an exacerbation could not be assessed.
    End point type
    Secondary
    End point timeframe
    through end of treatment
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    331
    345
    Units: Weeks
        median (confidence interval 95%)
    255.0 (190.0 to 9999)
    0 (0 to 9999)
    Statistical analysis title
    		 Proportional hazards regression model
    Statistical analysis description
    Null hypothesis: Hazard ratio (benralizumab vs Placebo) = 1
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8201
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.32

    Secondary: Change from baseline in COPD assessment tool (CAT) total score up to Week 56 of participants with >=3 exacerbations in the previous year.

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    End point title
    		 Change from baseline in COPD assessment tool (CAT) total score up to Week 56 of participants with >=3 exacerbations in the previous year.
    End point description
    The CAT is an 8-item PRO developed to measure the impact of COPD on health status. The instrument uses semantic differential 6-point response scales, which are defined by contrasting objectives to capture the impact of COPD. Content includes items related to cough, phlegm, chest tightness, breathlessness going up hills/stairs, activity limitation at home, confidence leaving home, sleep, and energy. The CAT total score is the sum of all item responses. Scores range from 0 to 40 with higher scores indicative of greater COPD impact on health status. A score cannot be calculated if >2 responses are missing; when one or two items are missing, their scores can be set to the average of the non-missing item scores.
    End point type
    Secondary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    241
    249
    Units: Score
        least squares mean (confidence interval 95%)
    -4.264 (-5.136 to -3.391)
    -2.391 (-3.260 to -1.523)
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in CAT total score change from baseline at 56 weeks (Benralizumab minus placebo) = 0
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.003
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.872
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.104
         upper limit
    		 -0.641

    Secondary: Change from baseline in COPD assessment tool (CAT) total score up to Week 56 of participants with >=2 exacerbations in the previous year.

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    End point title
    		 Change from baseline in COPD assessment tool (CAT) total score up to Week 56 of participants with >=2 exacerbations in the previous year.
    End point description
    The CAT is an 8-item PRO developed to measure the impact of COPD on health status. The instrument uses semantic differential 6-point response scales, which are defined by contrasting objectives to capture the impact of COPD. Content includes items related to cough, phlegm, chest tightness, breathlessness going up hills/stairs, activity limitation at home, confidence leaving home, sleep, and energy. The CAT total score is the sum of all item responses. Scores range from 0 to 40 with higher scores indicative of greater COPD impact on health status. A score cannot be calculated if >2 responses are missing; when one or two items are missing, their scores can be set to the average of the non-missing item scores.
    End point type
    Secondary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    331
    345
    Units: Score
        least squares mean (confidence interval 95%)
    -4.021 (-4.761 to -3.281)
    -2.178 (-2.909 to -1.447)
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in CAT total score change from baseline at 56 weeks (Benralizumab minus placebo) = 0
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0005
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.843
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.883
         upper limit
    		 -0.802

    Secondary: Change from baseline in Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS: COPD) total and domain scores at week 56 of participants with >=3 exacerbations in the previous year.

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    End point title
    		 Change from baseline in Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS: COPD) total and domain scores at week 56 of participants with >=3 exacerbations in the previous year.
    End point description
    The E-RS: COPD is an 11-item PRO developed to evaluate the severity of respiratory symptoms of COPD. The E-RS: COPD is a subset of items from the EXACT-PRO. The E-RS: COPD was designed to be captured as part of the daily EXACT-PRO assessment. Summation of E-RS: COPD item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity. In addition to the total score, symptom domain scores can be calculated for breathlessness (5 items; score range: 0–17), cough and sputum (3 items; score range: 0–11) and chest symptoms (3 items; score range: 0–12) by summing the responses of items within a respective domain. As with the total score, higher domain scores indicate greater severity.
    End point type
    Secondary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    241
    249
    Units: Score
    arithmetic mean (standard deviation)
        Total Score
    -2.32 ( 6.602 )
    -1.49 ( 5.343 )
        Breathlessness
    -0.76 ( 3.409 )
    -0.41 ( 2.839 )
        Cough and Sputum
    -0.77 ( 1.836 )
    -0.60 ( 1.593 )
        Chest Symptoms
    -0.78 ( 2.224 )
    -0.48 ( 1.850 )
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in E-RS: COPD total score at Week 56 (tezepelumab minus placebo) = 0
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    490
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1285
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -0.795
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.822
         upper limit
    		 0.231

    Secondary: Change from baseline in Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS: COPD) total and domain scores at week 56 of participants with >=2 exacerbations in the previous year.

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    End point title
    		 Change from baseline in Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS: COPD) total and domain scores at week 56 of participants with >=2 exacerbations in the previous year.
    End point description
    The E-RS: COPD is an 11-item PRO developed to evaluate the severity of respiratory symptoms of COPD. The E-RS: COPD is a subset of items from the EXACT-PRO. The E-RS: COPD was designed to be captured as part of the daily EXACT-PRO assessment. Summation of E-RS: COPD item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity. In addition to the total score, symptom domain scores can be calculated for breathlessness (5 items; score range: 0–17), cough and sputum (3 items; score range: 0–11) and chest symptoms (3 items; score range: 0–12) by summing the responses of items within a respective domain. As with the total score, higher domain scores indicate greater severity.
    End point type
    Secondary
    End point timeframe
    up to Week 56
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    331
    345
    Units: Score
    arithmetic mean (standard deviation)
        Total Score
    -1.95 ( 6.218 )
    -1.20 ( 5.245 )
        Breathlessness
    -0.57 ( 3.196 )
    -0.29 ( 2.691 )
        Cough and Sputum
    -0.67 ( 1.736 )
    -0.52 ( 1.576 )
        Chest Symptoms
    -0.70 ( 2.071 )
    -0.39 ( 1.849 )
    Statistical analysis title
    		 Repeated measures model
    Statistical analysis description
    Null Hypothesis: Difference in mean change from baseline in E-RS: COPD total score at Week 56 (tezepelumab minus placebo) = 0
    Comparison groups
    Benralizumab 100 mg v Placebo
    Number of subjects included in analysis
    676
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0931
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -0.722
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.565
         upper limit
    		 0.121

    Secondary: All-cause and respiratory-related mortality of participants with >=3 exacerbations in the previous year.

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    End point title
    		 All-cause and respiratory-related mortality of participants with >=3 exacerbations in the previous year.
    End point description
    Respiratory related causes of death are summarised based on the SOC = Respiratory, thoracic and mediastinal disorders. Exposure adjusted incidence rate (EAIR) of mortality is compared between treatment groups. EAIR per 100 patient-years is defined as number of subjects with a mortality divided by the total number of days at risk for mortality across all subjects in given treatment group, multiplied by 365.25 and then multiplied by 100. Total number of days at risk for death is defined as the duration from the first dose of IP to the date of death, or the duration from the first dose of IP to last visit for subjects without death.
    End point type
    Secondary
    End point timeframe
    Through end of treatment
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    241
    249
    Units: Exposure adjusted incidence rate
    number (not applicable)
        All causes mortality
    3.00
    5.05
        Respiratory-related mortality
    1.80
    2.32
    No statistical analyses for this end point

    Secondary: All-cause and respiratory-related mortality of participants with >=2 exacerbations in the previous year.

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    End point title
    		 All-cause and respiratory-related mortality of participants with >=2 exacerbations in the previous year.
    End point description
    Respiratory related causes of death are summarised based on the SOC = Respiratory, thoracic and mediastinal disorders. Exposure adjusted incidence rate (EAIR) of mortality is compared between treatment groups. EAIR per 100 patient-years is defined as number of subjects with a mortality divided by the total number of days at risk for mortality across all subjects in given treatment group, multiplied by 365.25 and then multiplied by 100. Total number of days at risk for death is defined as the duration from the first dose of IP to the date of death, or the duration from the first dose of IP to last visit for subjects without death.
    End point type
    Secondary
    End point timeframe
    Through end of treatment
    End point values
    		 Benralizumab 100 mg Placebo
    Number of subjects analysed
    331
    345
    Units: Exposure adjusted incidence rate
    number (not applicable)
        All causes mortality
    3.72
    4.62
        Respiratory-related mortality
    2.13
    2.31
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until last study visit
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Benralizumab 100 mg
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo Benralizumab 100 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    186 / 345 (53.91%)
    155 / 331 (46.83%)
         number of deaths (all causes)
    34
    28
         number of deaths resulting from adverse events
    34
    28
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign gastrointestinal neoplasm
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic neoplasm
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangiocarcinoma
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign small intestinal neoplasm
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    2 / 345 (0.58%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Lung neoplasm
         subjects affected / exposed
    2 / 345 (0.58%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    2 / 345 (0.58%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lip squamous cell carcinoma
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive lobular breast carcinoma
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma stage 0
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal adenoma
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 345 (0.00%)
    4 / 331 (1.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 345 (0.29%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    2 / 345 (0.58%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    2 / 345 (0.58%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage I
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma stage IV
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    High-grade B-cell lymphoma
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung carcinoma cell type unspecified stage II
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung squamous cell carcinoma stage I
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    2 / 345 (0.58%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 345 (0.00%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Chest discomfort
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 345 (0.29%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scrotal oedema
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic respiratory failure
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    103 / 345 (29.86%)
    87 / 331 (26.28%)
         occurrences causally related to treatment / all
    0 / 157
    0 / 170
         deaths causally related to treatment / all
    0 / 6
    0 / 8
    Bronchospasm
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    2 / 345 (0.58%)
    7 / 331 (2.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Dyspnoea
         subjects affected / exposed
    1 / 345 (0.29%)
    3 / 331 (0.91%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 345 (0.29%)
    3 / 331 (0.91%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal polyps
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercapnia
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    2 / 345 (0.58%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    4 / 345 (1.16%)
    3 / 331 (0.91%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    8 / 345 (2.32%)
    4 / 331 (1.21%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    Pulmonary mass
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychotic disorder
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Weight decreased
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram T wave peaked
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Compression fracture
         subjects affected / exposed
    1 / 345 (0.29%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 345 (0.00%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    2 / 345 (0.58%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Rib fracture
         subjects affected / exposed
    3 / 345 (0.87%)
    3 / 331 (0.91%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound complication
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue injury
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic injury
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    4 / 345 (1.16%)
    5 / 331 (1.51%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Angina unstable
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 345 (0.58%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Cardiac failure
         subjects affected / exposed
    4 / 345 (1.16%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Angina pectoris
         subjects affected / exposed
    2 / 345 (0.58%)
    3 / 331 (0.91%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery stenosis
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 345 (0.00%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    4 / 345 (1.16%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    Right ventricular failure
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart failure with reduced ejection fraction
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    0 / 345 (0.00%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachyarrhythmia
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Acquired syringomyelia
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain hypoxia
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 345 (0.29%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thalamus haemorrhage
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Blood loss anaemia
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    2 / 345 (0.58%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypereosinophilic syndrome
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Immune thrombocytopenia
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy mediastinal
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Optic neuropathy
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular hole
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiretinal membrane
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract cortical
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastric ulcer
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral hernia incarcerated
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    3 / 345 (0.87%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal adhesions
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoperitoneum
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal angiodysplasia
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    2 / 345 (0.58%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Ischaemic hepatitis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    2 / 345 (0.58%)
    3 / 331 (0.91%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    2 / 345 (0.58%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    4 / 345 (1.16%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal injury
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Renal artery stenosis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoporotic fracture
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteitis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 345 (0.29%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess sweat gland
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis infective
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    2 / 345 (0.58%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related bacteraemia
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    6 / 345 (1.74%)
    7 / 331 (2.11%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    21 / 345 (6.09%)
    29 / 331 (8.76%)
         occurrences causally related to treatment / all
    0 / 31
    0 / 35
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Helicobacter gastritis
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Focal peritonitis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia parainfluenzae viral
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia haemophilus
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    9 / 345 (2.61%)
    3 / 331 (0.91%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pneumonia acinetobacter
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    21 / 345 (6.09%)
    23 / 331 (6.95%)
         occurrences causally related to treatment / all
    0 / 28
    0 / 29
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Osteomyelitis
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia proteus
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    0 / 345 (0.00%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural pneumonia
         subjects affected / exposed
    2 / 345 (0.58%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    2 / 345 (0.58%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    5 / 345 (1.45%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Septic shock
         subjects affected / exposed
    4 / 345 (1.16%)
    3 / 331 (0.91%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis bacterial
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 345 (0.87%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethritis
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 345 (0.29%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    6 / 345 (1.74%)
    3 / 331 (0.91%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    COVID-19
         subjects affected / exposed
    5 / 345 (1.45%)
    6 / 331 (1.81%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 345 (0.29%)
    0 / 331 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 345 (0.00%)
    1 / 331 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    2 / 345 (0.58%)
    2 / 331 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Benralizumab 100 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    193 / 345 (55.94%)
    175 / 331 (52.87%)
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    35 / 345 (10.14%)
    15 / 331 (4.53%)
         occurrences all number
    39
    17
    Vascular disorders
    Hypertension
         subjects affected / exposed
    18 / 345 (5.22%)
    22 / 331 (6.65%)
         occurrences all number
    23
    25
    Nervous system disorders
    Headache
         subjects affected / exposed
    20 / 345 (5.80%)
    20 / 331 (6.04%)
         occurrences all number
    25
    28
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    18 / 345 (5.22%)
    14 / 331 (4.23%)
         occurrences all number
    21
    18
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    16 / 345 (4.64%)
    26 / 331 (7.85%)
         occurrences all number
    17
    32
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    19 / 345 (5.51%)
    10 / 331 (3.02%)
         occurrences all number
    19
    10
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    20 / 345 (5.80%)
    26 / 331 (7.85%)
         occurrences all number
    23
    28
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    59 / 345 (17.10%)
    44 / 331 (13.29%)
         occurrences all number
    99
    82
    Pneumonia
         subjects affected / exposed
    25 / 345 (7.25%)
    22 / 331 (6.65%)
         occurrences all number
    31
    28
    Upper respiratory tract infection
         subjects affected / exposed
    43 / 345 (12.46%)
    31 / 331 (9.37%)
         occurrences all number
    56
    77
    Urinary tract infection
         subjects affected / exposed
    26 / 345 (7.54%)
    23 / 331 (6.95%)
         occurrences all number
    37
    28
    COVID-19
         subjects affected / exposed
    47 / 345 (13.62%)
    48 / 331 (14.50%)
         occurrences all number
    56
    51

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Dec 2019
    Added an optional mechanistic sub-study, including serum biomarker assessments. An exploratory objective for this study to evaluate the effect of benralizumab 100 mg on rescue medication use was added. The inclusion and exclusion criteria were updated. The duration that patients must abstain from donating blood, plasma, or platelets after last dose of IP was changed. Multiplicity testing strategy was modified to strongly control for type 1 error rate at 0.05 level.
    29 Jul 2020
    The primary rationale for this amendment is to add study mitigation language which will provide sites with measures that may be implemented if a participant is not able to visit a study site to ensure that the clinical trial can continue whilst minimizing risk to the participant, maintaining compliance with GCP, and minimizing risks to the study integrity.
    19 Jan 2021
    The primary rationale for this amendment is to introduce optional self- administration of IP after week 56 and to update the requirement on the duration of inhaled triple (ICS/LABA/LAMA) therapy prior to enrolment (inclusion criterion #7).
    21 Jun 2022
    The primary rationale for this amendment is to address various impacts on the study as a result of the ongoing effects of the global COVID-19 pandemic. In addition to making recruitment more challenging, real-world evidence databases have demonstrated that the global response to the COVID pandemic has substantially impacted the expected rate of severe exacerbations. With the lower expected severe exacerbation rate, the original sample size justification to observe a treatment effect on the secondary endpoint of severe exacerbations is no longer valid. The study’s sample size has been revised to be dependent on the primary endpoint only (moderate and severe exacerbations), and the multiplicity testing strategy has been changed as a result. In the mechanistic sub-study, the pandemic-imposed challenges to the recruitment of the sub-study with no patient randomized to date, have led to the removal of the sub-study. Additional protocol modifications were added for clarification, simplification, and to reduce the patient’s burden.

    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
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