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    Clinical Trial Results:
    A randomised, double-blind, placebo-controlled, parallel group, multi-centre Phase IIa study in asthma patients comparing the efficacy and safety of once daily inhaled Interferon beta-1a to placebo, administered for 14 days after the onset of symptoms of an upper respiratory tract infection for the prevention of severe exacerbations

    Summary
    EudraCT number
    2014-005084-32
    Trial protocol
    GB   ES   FR  
    Global end of trial date
    24 Nov 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    23 Nov 2017
    First version publication date
    23 Nov 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D6230C00001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02491684
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    Gärturnavägen 1, Södertälje, Sweden, SE-151 85
    Public contact
    Medical Science Director, AstraZeneca, ClinicalTrialTransparency@astrazeneca.com
    Scientific contact
    Medical Science Director, AstraZeneca, ClinicalTrialTransparency@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
    24 Nov 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Nov 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Nov 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of inhaled interferon beta-1a compared to placebo in preventing severe exacerbations during the 14 days of treatment following onset of an upper respiratory tract infection in asthmatic patients, on top of their regular asthma maintenance treatment.
    Protection of trial subjects
    The study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Council for Harmonisation Good Clinical Practice and applicable regulatory requirements and the AstraZeneca policy on Bioethics and Human Biological Samples.
    Background therapy
    Patients continued to receive their regular asthma maintenance treatment including medium to high dose inhaled corticosteroids (> 250 micrograms fluticasone dry powder formulation equivalents total daily dose), and a second controller medication (long-acting beta2-agonists).
    Evidence for comparator
    -
    Actual start date of recruitment
    21 Jul 2015
    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
    Argentina: 48
    Country: Number of subjects enrolled
    United Kingdom: 31
    Country: Number of subjects enrolled
    Korea, Republic of: 21
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    Australia: 6
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Colombia: 3
    Worldwide total number of subjects
    121
    EEA total number of subjects
    43
    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)
    107
    From 65 to 84 years
    14
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    First patient enrolled: 21 July 2015; Last Patient Last Visit: 24 November 2016. The study was performed at 39 sites in 7 countries including Argentina, Australia, Colombia, France, South Korea, Spain and the United Kingdom.

    Pre-assignment
    Screening details
    349 patients enrolled (signed informed consent) and 228 were not randomised. 121 patients met randomisation criteria and entered the pre-treatment phase. Patients were treated after developing symptoms of an upper respiratory tract infection (URTI) if they met all the inclusion criteria and none of the exclusion criteria for the treatment phase.

    Period 1
    Period 1 title
    Pre-treatment Phase
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    AZD9412
    Arm description
    Patients were randomised to receive investigational product AZD9412 (interferon beta-1a) in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the AZD9412 group received 6 Million International Units (MIU) (24 micrograms [mcg] metered dose) inhaled AZD9412 once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an electronic Patient Reported Outcome (ePRO) device at home.
    Arm type
    Experimental

    Investigational medicinal product name
    AZD9412 nebuliser solution 48 mcg/mL
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Patients received 6 MIU (24 mcg metered dose) once daily for 14 days.

    Arm title
    Placebo
    Arm description
    Patients were randomised to receive placebo in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or the flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the placebo group received 6 MIU (24 mcg metered dose) inhaled placebo once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an ePRO device at home.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo nebuliser solution
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Patients received 6 MIU (24 mcg metered dose) once daily for 14 days.

    Number of subjects in period 1
    AZD9412 Placebo
    Started
    61
    60
    Completed
    61
    60
    Period 2
    Period 2 title
    Treatment Phase
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    AZD9412
    Arm description
    Patients were randomised to receive investigational product AZD9412 (interferon beta-1a) in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the AZD9412 group received 6 Million International Units (MIU) (24 micrograms [mcg] metered dose) inhaled AZD9412 once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an electronic Patient Reported Outcome (ePRO) device at home.
    Arm type
    Experimental

    Investigational medicinal product name
    AZD9412 nebuliser solution 48 mcg/mL
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Patients received 6 MIU (24 mcg metered dose) once daily for 14 days.

    Arm title
    Placebo
    Arm description
    Patients were randomised to receive placebo in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or the flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the placebo group received 6 MIU (24 mcg metered dose) inhaled placebo once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an ePRO device at home.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo nebuliser solution
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nebuliser solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    Patients received 6 MIU (24 mcg metered dose) once daily for 14 days.

    Number of subjects in period 2
    AZD9412 Placebo
    Started
    61
    60
    Completed
    58
    57
    Not completed
    3
    3
         Investigator and Sponsor decision
    -
    1
         Incorrect randomisation
    1
    -
         Adverse event, non-fatal
    2
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    AZD9412
    Reporting group description
    Patients were randomised to receive investigational product AZD9412 (interferon beta-1a) in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the AZD9412 group received 6 Million International Units (MIU) (24 micrograms [mcg] metered dose) inhaled AZD9412 once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an electronic Patient Reported Outcome (ePRO) device at home.

    Reporting group title
    Placebo
    Reporting group description
    Patients were randomised to receive placebo in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or the flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the placebo group received 6 MIU (24 mcg metered dose) inhaled placebo once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an ePRO device at home.

    Reporting group values
    AZD9412 Placebo Total
    Number of subjects
    61 60 121
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    53 54 107
        From 65-84 years
    8 6 14
        85 years and over
    0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    47.8 ± 12.95 47.7 ± 14.10 -
    Sex: Female, Male
    Units: Subjects
        Female
    48 43 91
        Male
    13 17 30

    End points

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    End points reporting groups
    Reporting group title
    AZD9412
    Reporting group description
    Patients were randomised to receive investigational product AZD9412 (interferon beta-1a) in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the AZD9412 group received 6 Million International Units (MIU) (24 micrograms [mcg] metered dose) inhaled AZD9412 once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an electronic Patient Reported Outcome (ePRO) device at home.

    Reporting group title
    Placebo
    Reporting group description
    Patients were randomised to receive placebo in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or the flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the placebo group received 6 MIU (24 mcg metered dose) inhaled placebo once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an ePRO device at home.
    Reporting group title
    AZD9412
    Reporting group description
    Patients were randomised to receive investigational product AZD9412 (interferon beta-1a) in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the AZD9412 group received 6 Million International Units (MIU) (24 micrograms [mcg] metered dose) inhaled AZD9412 once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an electronic Patient Reported Outcome (ePRO) device at home.

    Reporting group title
    Placebo
    Reporting group description
    Patients were randomised to receive placebo in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or the flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the placebo group received 6 MIU (24 mcg metered dose) inhaled placebo once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an ePRO device at home.

    Primary: Proportion of patients with a severe asthma exacerbation during 14 days of treatment

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    End point title
    Proportion of patients with a severe asthma exacerbation during 14 days of treatment
    End point description
    Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing severe exacerbations during the 14 day treatment phase following the onset of an URTI in asthmatic patients. A severe exacerbation was defined as worsening asthma symptoms and a) use of systemic corticosteroids (or a temporary increase of at least 2-fold in a stable oral corticosteroid background dose) for at least 3 consecutive days and/or b) an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or c) an in-patient hospitalisation due to asthma requiring at least 1 dose of systemic corticosteroids. The number of patients with severe asthma exacerbations with onset during the treatment phase is presented for each treatment group. The Intention to treat (ITT) analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.
    End point type
    Primary
    End point timeframe
    Day 1 - 14 of the treatment phase.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: Number of patients
    7
    5
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.645
    Method
    log-binomial regression model
    Parameter type
    Ratio of proportions
    Point estimate
    1.29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.43
         upper limit
    3.85

    Secondary: Proportion of patients with severe asthma exacerbations within 7 and 30 days following randomisation

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    End point title
    Proportion of patients with severe asthma exacerbations within 7 and 30 days following randomisation
    End point description
    Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing severe exacerbations within 7 and 30 days after the start of treatment (Day 1). A severe exacerbation was defined as worsening asthma symptoms and a) use of systemic corticosteroids (or a temporary increase of at least 2-fold in a stable oral corticosteroid background dose) for at least 3 consecutive days and/or b) an unscheduled visit or emergency room visit due to asthma symptoms that required at least 1 dose of systemic corticosteroids and/or c) an in-patient hospitalisation due to asthma requiring at least 1 dose of systemic corticosteroids. The numbers of patients with severe asthma exacerbations with onset during Days 1 - 7 and Days 1 - 30 are presented for each treatment group. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.
    End point type
    Secondary
    End point timeframe
    Day 1 of treatment phase up to 30 days post-randomisation.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: Number of patients
        Days 1 - 7|
    4
    2
        Days 1 - 30|
    8
    6
    Statistical analysis title
    AZD9412 versus Placebo for Days 1 - 7
    Statistical analysis description
    Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.411
    Method
    log-binomial regression model
    Parameter type
    Ratio of proportions
    Point estimate
    1.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.39
         upper limit
    9.89
    Statistical analysis title
    AZD9412 versus Placebo for Days 1 - 30
    Statistical analysis description
    Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.659
    Method
    log-binomial regression model
    Parameter type
    Ratio of proportions
    Point estimate
    1.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.46
         upper limit
    3.41

    Secondary: Proportion of patients with moderate asthma exacerbation within 7, 14 and 30 days following randomisation

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    End point title
    Proportion of patients with moderate asthma exacerbation within 7, 14 and 30 days following randomisation
    End point description
    Evaluation of the efficacy of inhaled AZD9412 compared to placebo in preventing moderate exacerbations within 7, 14 and 30 days after the start of treatment (Day 1). A moderate exacerbation was defined as a temporary increase in maintenance therapy in order to prevent a severe event supported by a sustained (2 or more days) worsening in at least one key control metric, including asthma score, rescue use, night time awakening or morning peak expiratory flow. The numbers of patients with moderate exacerbations with onset during Days 1 - 7, Days 1 - 14 and Days 1 - 30 are presented for each treatment group. With respect to the Day 1-7 analysis, the model did not converge so the analysis could not be performed. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.
    End point type
    Secondary
    End point timeframe
    Day 1 of treatment phase up to 30 days post-randomisation.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: Number of patients
        Days 1 - 7|
    0
    1
        Days 1 - 14|
    1
    1
        Days 1 - 30|
    1
    1
    Statistical analysis title
    AZD9412 versus Placebo for Days 1 - 14
    Statistical analysis description
    Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.944
    Method
    log-binomial regression model
    Parameter type
    Ratio of proportions
    Point estimate
    1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.08
         upper limit
    15.79
    Statistical analysis title
    AZD9412 versus Placebo for Days 1 - 30
    Statistical analysis description
    Proportions of patients with exacerbations are compared using a log-binomial regression model with treatment group and region as factors.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.944
    Method
    log-binomial regression model
    Parameter type
    Ratio of proportions
    Point estimate
    1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.08
         upper limit
    15.79

    Secondary: Time to first severe asthma exacerbation during 30 days following randomisation

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    End point title
    Time to first severe asthma exacerbation during 30 days following randomisation
    End point description
    The time to first event was calculated as start date of events - date of randomisation + 1. Patients with no observed event were censored at the date of their last visit, or for lost-to-follow-up patients, at the last time point after which an event could not be assessed. The median time to first exacerbation was not calculated in either treatment group due to low numbers of events. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.
    End point type
    Secondary
    End point timeframe
    From Day 1 of treatment phase up to 30 days post-randomisation.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: Days
        median (full range (min-max))
    99999999 (99999999 to 99999999)
    99999999 (99999999 to 99999999)
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of time to first severe exacerbation within 30 days of treatment start.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.634
    Method
    Regression, Cox
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.45
         upper limit
    3.77

    Secondary: Time to first moderate asthma exacerbation during 30 days following randomisation

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    End point title
    Time to first moderate asthma exacerbation during 30 days following randomisation
    End point description
    The time to first event was calculated as start date of events - date of randomisation + 1. Patients with no observed event were censored at the date of their last visit, or for lost-to-follow-up patients, at the last time point after which an event could not be assessed. The median time to first exacerbation was not calculated in either treatment group due to low numbers of events. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available.
    End point type
    Secondary
    End point timeframe
    From Day 1 of treatment phase up to 30 days post-randomisation.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: Days
        median (full range (min-max))
    99999999 (99999999 to 99999999)
    99999999 (99999999 to 99999999)
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of time to first moderate exacerbation within 30 days of treatment start.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.973
    Method
    Regression, Cox
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.07
         upper limit
    16.78

    Secondary: Duration of moderate or severe exacerbations

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    End point title
    Duration of moderate or severe exacerbations
    End point description
    The duration of each individual moderate or severe exacerbation was calculated as: Cessation date of exacerbation - Start date of exacerbation + 1. The start date of a severe exacerbation was defined as the start date of systemic corticosteroids or increase of systemic corticosteroids or emergency room visit or hospital admission, whichever occurred first. The stop date was defined as the last day of systemic corticosteroids/increase of systemic corticosteroids or hospital discharge, whichever occurred last. The start date of a moderate exacerbation was defined as the first day of increase in temporary maintenance therapy. The stop date was defined as the last day of this treatment. The mean duration of moderate or severe exacerbations is presented. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available. The number of patients in the analysis are those with at least 1 exacerbation.
    End point type
    Secondary
    End point timeframe
    Day 1 of treatment phase up to 30 days post-randomisation.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    8
    6
    Units: Days
        arithmetic mean (standard deviation)
    10 ± 7.7
    8 ± 4.5
    No statistical analyses for this end point

    Secondary: Change in asthma control from baseline up to 30 days as measured by the Asthma Control Questionnaire (ACQ-6)

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    End point title
    Change in asthma control from baseline up to 30 days as measured by the Asthma Control Questionnaire (ACQ-6)
    End point description
    The ACQ-6 consists of 6 questions to assess asthma control, each question measured on a 7-point scale scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 total score is computed as the un-weighted mean of the responses to the 6 questions. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The change from baseline at Visit 4 (Day 7 +/- 1), at Visit 6 (Day 14 +/- 1) and at Visit 8 (Day 30) is presented for the total score and for each of the 6 questions. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available. Patients with non-missing values were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after start of treatment phase.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: Units on a Scale
    least squares mean (standard error)
        ACQ-6 Total Score, Visit 4|
    0.02 ± 0.11
    -0.07 ± 0.12
        ACQ-6 Total Score, Visit 6|
    -0.15 ± 0.14
    -0.21 ± 0.14
        ACQ-6 Total Score, Visit 8|
    -0.42 ± 0.15
    -0.35 ± 0.15
        Q1: Woken by Asthma, Visit 4|
    0.09 ± 0.18
    -0.09 ± 0.18
        Q1: Woken by Asthma, Visit 6|
    0.15 ± 0.20
    -0.28 ± 0.21
        Q1: Woken by Asthma, Visit 8|
    -0.50 ± 0.18
    -0.32 ± 0.18
        Q2: Symptoms at Awakening, Visit 4|
    0.06 ± 0.18
    -0.17 ± 0.18
        Q2: Symptoms at Awakening, Visit 6|
    -0.40 ± 0.16
    -0.33 ± 0.17
        Q2: Symptoms at Awakening, Visit 8|
    -0.76 ± 0.19
    -0.47 ± 0.19
        Q3: Limited in Activities, Visit 4|
    0.04 ± 0.15
    0.06 ± 0.15
        Q3: Limited in Activities, Visit 6|
    -0.12 ± 0.17
    0.16 ± 0.18
        Q3: Limited in Activities, Visit 8|
    -0.43 ± 0.18
    -0.33 ± 0.18
        Q4: Shortness of Breath, Visit 4|
    -0.13 ± 0.15
    -0.11 ± 0.16
        Q4: Shortness of Breath, Visit 6|
    -0.34 ± 0.19
    -0.38 ± 0.21
        Q4: Shortness of Breath, Visit 8|
    -0.46 ± 0.18
    -0.37 ± 0.19
        Q5: Wheeze, Visit 4|
    0.13 ± 0.17
    0.08 ± 0.17
        Q5: Wheeze, Visit 6|
    -0.17 ± 0.17
    -0.17 ± 0.18
        Q5: Wheeze, Visit 8|
    -0.33 ± 0.21
    -0.42 ± 0.21
        Q6: Puffs of Short-Acting Bronchodilator; Visit 4|
    0.06 ± 0.13
    0.00 ± 0.14
        Q6: Puffs of Short-Acting Bronchodilator; Visit 6|
    0.07 ± 0.14
    -0.11 ± 0.15
        Q6: Puffs of Short-Acting Bronchodilator; Visit 8|
    0.04 ± 0.14
    -0.03 ± 0.14
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of change from baseline in total score at Visit 4.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.495
    Method
    ANCOVA
    Parameter type
    Least Squares (LS) Mean difference
    Point estimate
    0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.17
         upper limit
    0.35
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of change from baseline in total score at Visit 6.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.715
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    0.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.26
         upper limit
    0.38
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of change from baseline in total score at Visit 8.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.687
    Method
    ANCOVA
    Parameter type
    LS Mean Difference
    Point estimate
    -0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.42
         upper limit
    0.28

    Secondary: AUC for change in daytime and night-time asthma symptom score from baseline up to 30 days

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    End point title
    AUC for change in daytime and night-time asthma symptom score from baseline up to 30 days
    End point description
    Asthma symptoms during night-time and daytime were recorded by the patient each morning and evening in the Asthma Daily Diary on a daily basis. Symptoms were recorded using a scale of 0 to 3 where 0 indicates no asthma symptoms up to an absolute score of 3. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The total daily asthma symptom score was calculated by taking the sum of the night-time and daytime asthma scores recorded each day. The outcome variable is the area under the curve (AUC) for change from baseline in day-time, night-time and total daily asthma symptom scores over Days 1-14, Days 1-7, Days 8-14 and Days 15-30. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available. Patients with non-missing values were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after start of treatment phase.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: Units on Scale
    least squares mean (standard error)
        Total asthma score, Days 1-14|
    -0.20 ± 0.16
    -0.31 ± 0.16
        Total asthma score, Days 1-7|
    -0.11 ± 0.13
    -0.22 ± 0.13
        Total asthma score, Days 8-14|
    -0.40 ± 0.15
    -0.41 ± 0.16
        Total asthma score, Days 15-30|
    -0.77 ± 0.16
    -0.77 ± 0.16
        Daytime asthma score, Days 1-14|
    -0.22 ± 0.07
    -0.26 ± 0.07
        Daytime asthma score, Days 1-7|
    -0.17 ± 0.06
    -0.17 ± 0.06
        Daytime asthma score, Days 8-14|
    -0.23 ± 0.07
    -0.27 ± 0.07
        Daytime asthma score, Days 15-30|
    -0.44 ± 0.07
    -0.41 ± 0.07
        Night-time asthma score, Days 1-14|
    -0.17 ± 0.07
    -0.16 ± 0.08
        Night-time asthma score, Days 1-7|
    -0.10 ± 0.06
    -0.09 ± 0.07
        Night-time asthma score, Days 8-14|
    -0.20 ± 0.07
    -0.17 ± 0.08
        Night-time asthma score, Days 15-30|
    -0.44 ± 0.09
    -0.39 ± 0.09
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline in total score over Days 1-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.516
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.23
         upper limit
    0.45
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline in total score over Days 1-7.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.417
    Method
    ANCOVA
    Parameter type
    LS mean difference
    Point estimate
    0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.16
         upper limit
    0.37
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline in total score over Days 8-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.954
    Method
    ANCOVA
    Parameter type
    LS mean difference
    Point estimate
    0.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.34
         upper limit
    0.36
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline in total score over Days 15-30.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.985
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.35
         upper limit
    0.35

    Secondary: Change in the proportion of night-time awakening using the ePRO questionnaire from baseline up to 30 days

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    End point title
    Change in the proportion of night-time awakening using the ePRO questionnaire from baseline up to 30 days
    End point description
    Night-time awakenings due to asthma symptoms were recorded by the patient in the Asthma Daily Diary each morning by answering the question whether he/she woke up during the night due to asthma symptoms with a 'yes' or 'no' response. Biweekly means were calculated as the percentages of times the subject answered 'yes' over a period of 14 sequential days. Biweekly means are presented for the periods over Days 2-15 and Days 16-30. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available. Patients with non-missing values were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after start of treatment phase.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: Percentage of 'yes' responses
    arithmetic mean (standard deviation)
        Days 2-15|
    22.3 ± 30.42
    24.8 ± 29.77
        Days 16-30|
    15.2 ± 26.79
    15.9 ± 26.34
    No statistical analyses for this end point

    Secondary: Change in health-related quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) from baseline up to 30 days

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    End point title
    Change in health-related quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ[S]) from baseline up to 30 days
    End point description
    The AQLQ(S) was used to assess health-related quality of life and consisted of 32 questions. Patients were asked to score each of the questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The questions were allocated to 4 domains assessing: 1) activity limitation, 2) symptoms, 3) emotional function, and 4) environmental stimuli The overall score was calculated as the mean of the responses to all questions. The mean change in overall score from baseline at Visit 6 (Day 14+/-1) and Visit 8 (Day 30) are presented. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available. Patients with non-missing values were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after start of treatment phase.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: Units on Scale
    least squares mean (standard error)
        Overall Score Visit 6|
    0.28 ± 0.13
    0.35 ± 0.14
        Overall Score Visit 8|
    0.43 ± 0.16
    0.53 ± 0.16
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of change from baseline in overall score at Visit 6.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.66
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    -0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.38
         upper limit
    0.24
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of change from baseline in overall score at Visit 8.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.624
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    -0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.48
         upper limit
    0.29

    Secondary: AUC for change in daytime and night-time reliever medication use from baseline up to 14 days

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    End point title
    AUC for change in daytime and night-time reliever medication use from baseline up to 14 days
    End point description
    Patients recorded the number of reliever medication inhalations taken twice daily in the Asthma Daily Diary. The number of inhalations taken between the morning and evening lung function assessments were recorded in the evening. The number of inhalations taken between the evening and morning lung function assessments were recorded in the morning. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The AUC for change from baseline over Days 1-14 (inclusive of Days 1 and 14) is presented. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available. Patients with non-missing values were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From baseline up to Day 14 of treatment phase.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    52
    48
    Units: Inhalations
        least squares mean (standard error)
    -0.12 ± 0.46
    -0.67 ± 0.48
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 1-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.309
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.51
         upper limit
    1.59

    Secondary: AUC for change in the morning Peak Expiratory Flow (PEF) from baseline to up to 30 days

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    End point title
    AUC for change in the morning Peak Expiratory Flow (PEF) from baseline to up to 30 days
    End point description
    Patients measured morning PEF at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available. Patients with non-missing values were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after start of treatment phase.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: litres/minute (l/min)
    least squares mean (standard error)
        Days 1-14|
    9.56 ± 14.02
    -7.42 ± 13.91
        Days 1-7|
    19.66 ± 9.66
    0.31 ± 9.11
        Days 8-14|
    7.03 ± 15.90
    -7.35 ± 15.80
        Days 15-30|
    32.75 ± 15.35
    13.49 ± 14.82
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 1-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.059
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    16.98
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.63
         upper limit
    34.6
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 1-7.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.01
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    19.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.66
         upper limit
    34.05
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 8-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.153
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    14.38
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.44
         upper limit
    34.2
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 15-30.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.096
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    19.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.44
         upper limit
    41.97

    Secondary: AUC for change in the morning Forced Expiratory Volume in 1 second (FEV1) from baseline up to 30 days

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    End point title
    AUC for change in the morning Forced Expiratory Volume in 1 second (FEV1) from baseline up to 30 days
    End point description
    Patients measured morning FEV1 at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available. Patients with non-missing values were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after start of treatment phase.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: litres
    least squares mean (standard error)
        Days 1-14|
    -0.00 ± 0.08
    -0.08 ± 0.08
        Days 1-7|
    0.10 ± 0.06
    0.02 ± 0.06
        Days 8-14|
    -0.03 ± 0.08
    -0.09 ± 0.08
        Days 15-30|
    0.15 ± 0.09
    0.04 ± 0.08
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 1-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.161
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.03
         upper limit
    0.17
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 1-7.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.087
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.01
         upper limit
    0.17
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 8-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.28
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.05
         upper limit
    0.16
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 15-30.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.086
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.02
         upper limit
    0.24

    Secondary: AUC for change in the evening PEF from baseline to up to 30 days

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    End point title
    AUC for change in the evening PEF from baseline to up to 30 days
    End point description
    Patients measured evening PEF at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available. Patients with non-missing values were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after start of treatment phase.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: l/min
    least squares mean (standard error)
        Days 1-14|
    10.96 ± 12.58
    -0.73 ± 11.88
        Days 1-7|
    8.78 ± 9.87
    -2.41 ± 9.30
        Days 8-14|
    8.49 ± 13.09
    -2.66 ± 12.55
        Days 15-30|
    11.88 ± 15.70
    -5.25 ± 15.13
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 1-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.211
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    11.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.76
         upper limit
    30.14
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 1-7.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.125
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    11.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.18
         upper limit
    25.56
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 8-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.277
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    11.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.08
         upper limit
    31.36
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 15-30.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.161
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    17.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.92
         upper limit
    41.18

    Secondary: AUC for change in the evening FEV1 from baseline up to 30 days

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    End point title
    AUC for change in the evening FEV1 from baseline up to 30 days
    End point description
    Patients measured evening FEV1 at home and recorded the results using the ePRO device. Baseline assessments were taken as the last non-missing assessment prior to randomisation. The mean AUC for change from baseline is presented for the periods Days 1-14, 1-7, 8-14 and 15-30. The ITT analysis set consisted of all randomised patients who received at least 1 dose of investigational product and had some post-dose data available. Patients with non-missing values were included in the analysis.
    End point type
    Secondary
    End point timeframe
    From baseline up to 30 days after start of treatment phase.
    End point values
    AZD9412 Placebo
    Number of subjects analysed
    61
    60
    Units: litres
    least squares mean (standard error)
        Days 1-14|
    -0.01 ± 0.07
    -0.07 ± 0.07
        Days 1-7|
    0.01 ± 0.07
    -0.03 ± 0.07
        Days 8-14|
    -0.02 ± 0.07
    -0.08 ± 0.07
        Days 15-30|
    0.02 ± 0.08
    -0.08 ± 0.08
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 1-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.287
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.05
         upper limit
    0.16
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 1-7.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.457
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.06
         upper limit
    0.14
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 8-14.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.315
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.05
         upper limit
    0.16
    Statistical analysis title
    AZD9412 versus Placebo
    Statistical analysis description
    Analysis of AUC for change from baseline over Days 15-30.
    Comparison groups
    AZD9412 v Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.134
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    0.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.03
         upper limit
    0.22

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment emergent adverse events were collected from the first day of study treatment up to the last date of follow-up (approximately 30 days).
    Adverse event reporting additional description
    The safety analysis set consisted of all randomised patients who received at least 1 dose of investigational product and with post-dose data available.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Patients were randomised to receive placebo in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or the flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the placebo group received 6 MIU (24 mcg metered dose) inhaled placebo once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an ePRO device at home.

    Reporting group title
    AZD9412
    Reporting group description
    Patients were randomised to receive investigational product AZD9412 (interferon beta-1a) in the treatment phase. Eligible patients entered the pre-treatment phase until they developed symptoms of a common cold or flu (URTI). Patients were evaluated at a study site for eligibility to enter the treatment phase as soon as possible but no later than 48 hours after the onset of the first symptoms of an URTI. Patients randomised to the AZD9412 group received 6 Million International Units (MIU) (24 micrograms [mcg] metered dose) inhaled AZD9412 once daily for 14 days, delivered by the I-neb® device. Patients continued their regular asthma maintenance treatment, and were assessed for exacerbations, changes in respiratory symptoms and reliever medication use using an electronic Patient Reported Outcome (ePRO) device at home.

    Serious adverse events
    Placebo AZD9412
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 60 (0.00%)
    3 / 61 (4.92%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 60 (0.00%)
    3 / 61 (4.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Placebo AZD9412
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    20 / 60 (33.33%)
    27 / 61 (44.26%)
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Asthenia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Oedema peripheral
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Injury associated with device
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Influenza like illness
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Depressed mood
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Emotional distress
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Mood altered
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Panic attack
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Muscle strain
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Mouth injury
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Blood pressure decreased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Glycosylated haemoglobin increased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Pulmonary function test decreased
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    2
    Asthma
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 61 (1.64%)
         occurrences all number
    5
    1
    Dysphonia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Cough
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences all number
    1
    3
    Hiccups
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Dyspnoea
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 61 (1.64%)
         occurrences all number
    2
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 61 (3.28%)
         occurrences all number
    0
    2
    Nasal congestion
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 61 (3.28%)
         occurrences all number
    0
    2
    Sinus pain
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Upper-airway cough syndrome
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Throat irritation
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Wheezing
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences all number
    2
    1
    Blood and lymphatic system disorders
    Eosinophilia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Lymphadenopathy
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 60 (5.00%)
    2 / 61 (3.28%)
         occurrences all number
    3
    2
    Tremor
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Blepharospasm
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Periorbital oedema
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    3
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 61 (3.28%)
         occurrences all number
    0
    2
    Diarrhoea
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 61 (3.28%)
         occurrences all number
    0
    2
    Gastritis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences all number
    1
    1
    Odynophagia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences all number
    1
    1
    Pruritus generalised
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences all number
    1
    1
    Back pain
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    2
    Musculoskeletal pain
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Osteoarthritis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Pain in jaw
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Tendonitis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 60 (1.67%)
    5 / 61 (8.20%)
         occurrences all number
    1
    5
    Conjunctivitis bacterial
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Ear infection
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Laryngitis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 60 (1.67%)
    2 / 61 (3.28%)
         occurrences all number
    1
    2
    Rhinitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Sinusitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0
    Tooth infection
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 61 (1.64%)
         occurrences all number
    1
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 61 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jan 2016
    -To clarify the requirement for stable maintenance treatment during the 12 months prior to inclusion. -To include mannitol challenge as an acceptable challenge method for asthma diagnosis. -Requirement to demonstrate acceptable technique when using ePRO device, home spirometer and I-neb added. -To clarify that patients with a diagnosis of active tuberculosis must not be included and that patients with CT/chest X-ray findings indicating bronchiectasis which in the opinion of the Investigator were not clinically significant could be enrolled at the discretion of the Investigator. -addition of exclusion criterion to ensure long enough washout for drugs with a long half-life. -clarification on systolic blood pressure limits, reliever medication use and pregnancy testing.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was terminated early due to the lower than expected rate of severe exacerbations in the study as a whole, and due to the observed lack of differential effect at interim analysis.
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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