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    Clinical Trial Results:
    A Multicentre, Randomized, Double-blind, Parallel Group, Placebo Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Tralokinumab in Reducing Oral Corticosteroid Use in Adults and Adolescents with Oral Corticosteroid dependent Asthma (TROPOS)

    Summary
    EudraCT number
    2014-001391-54
    Trial protocol
    DE   NL   BE   FR   PL  
    Global end of trial date
    07 Sep 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    15 Mar 2018
    First version publication date
    15 Mar 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D2210C00013
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02281357
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    200 Orchard Ridge Drive, Gaithersburg, United States, MD 20878
    Public contact
    Global Clinical Lead, AstraZeneca, 1 3013980582, ClinicalTrialTransparency@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, 1 3013980582, ClinicalTrialTransparency@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000782-PIP01-09
    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
    07 Sep 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Sep 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Sep 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effect of tralokinumab compared to placebo in reducing the prescribed oral corticosteroid (OCS) maintenance dose in adult and adolescent patients in the primary population with asthma requiring chronic treatment with maintenance OCS in addition to inhaled corticosteroid (ICS) plus long-acting β2-agonists (LABA).
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council on Harmonisation / Good Clinical Practice, applicable regulatory requirements and the AstraZeneca policy on Bioethics.
    Background therapy
    Patients were maintained on their currently prescribed ICS-LABA therapy and any additional maintenance asthma controller medications throughout the study period.
    Evidence for comparator
    -
    Actual start date of recruitment
    19 Feb 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 42
    Country: Number of subjects enrolled
    Ukraine: 24
    Country: Number of subjects enrolled
    Germany: 21
    Country: Number of subjects enrolled
    France: 21
    Country: Number of subjects enrolled
    United States: 19
    Country: Number of subjects enrolled
    Netherlands: 9
    Country: Number of subjects enrolled
    Belgium: 4
    Worldwide total number of subjects
    140
    EEA total number of subjects
    97
    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)
    1
    Adults (18-64 years)
    113
    From 65 to 84 years
    26
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    First patient enrolled: 19 February 2015; Last patient last visit: 07 September 2017. Study performed at 56 sites in 7 countries.

    Pre-assignment
    Screening details
    218 patients signed informed consent. 140 patients were randomised and all those randomised received study treatment. Prior to randomisation, patients completed a run-in period or run-in/OCS optimisation period (reached minimum effective dose of OCS and remained stable on that dose for 2 weeks). Primary population was the full analysis set (FAS).

    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, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Tralokinumab
    Arm description
    Tralokinumab 300 milligrams (mg) administered by subcutaneous (SC) injection every two weeks (Q2W) over a 40-week treatment period.
    Arm type
    Experimental

    Investigational medicinal product name
    Tralokinumab
    Investigational medicinal product code
    CAT-354
    Other name
    Tralo
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    150 milligrams/millilitre (mg/mL) solution for injection in an accessorised pre-filled syringe, 1.0 mL fill volume. Each patient received 2 SC injections of 150 mg tralokinumab at each dosing interval to receive a total dose of 300 mg.

    Arm title
    Placebo
    Arm description
    Placebo was administered by SC injection over a 40-week treatment period.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo solution for injection in an accessorised pre-filled syringe, 1.0 mL fill volume. Each patient received 2 SC injections of placebo at each dosing interval.

    Number of subjects in period 1
    Tralokinumab Placebo
    Started
    70
    70
    Completed
    63
    66
    Not completed
    7
    4
         Adverse event, non-fatal
    2
    1
         Consent withdrawn by subject
    4
    3
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tralokinumab
    Reporting group description
    Tralokinumab 300 milligrams (mg) administered by subcutaneous (SC) injection every two weeks (Q2W) over a 40-week treatment period.

    Reporting group title
    Placebo
    Reporting group description
    Placebo was administered by SC injection over a 40-week treatment period.

    Reporting group values
    Tralokinumab Placebo Total
    Number of subjects
    70 70 140
    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)
    1 0 1
        Adults (18-64 years)
    58 55 113
        From 65-84 years
    11 15 26
        85 years and over
    0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    54.0 ± 11.05 55.4 ± 10.26 -
    Sex: Female, Male
    Units: Subjects
        Female
    48 39 87
        Male
    22 31 53
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    1 0 1
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Black or African American
    2 5 7
        White
    66 63 129
        More than one race
    0 0 0
        Unknown or Not Reported
    1 2 3

    End points

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    End points reporting groups
    Reporting group title
    Tralokinumab
    Reporting group description
    Tralokinumab 300 milligrams (mg) administered by subcutaneous (SC) injection every two weeks (Q2W) over a 40-week treatment period.

    Reporting group title
    Placebo
    Reporting group description
    Placebo was administered by SC injection over a 40-week treatment period.

    Primary: Percent change from baseline in the final daily, average, OCS dose at Week 40 while not losing asthma control.

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    End point title
    Percent change from baseline in the final daily, average, OCS dose at Week 40 while not losing asthma control.
    End point description
    The 40-week treatment period consisted of 3 phases: an induction phase (Week 0 to Week 12) where patients remained on their optimised OCS dose; an OCS reduction phase (Week 12 to Week 32) where OCS dose reduction could have started at Week 12 with the possibility of dose titration every 4 weeks to reach the lowest possible OCS dose; and a maintenance phase (Week 32 to Week 40) where patients remained on the OCS dose reached at Week 32 to demonstrate asthma control was maintained after achieving the lowest OCS dose. The least squares (LS) mean percent change from baseline in average daily OCS dose is presented for the FAS, comprising all randomised patients who received at least one dose of study treatment. The average OCS dose was defined as {(Final daily average dose - baseline daily average dose)/baseline daily average dose}*100%.
    End point type
    Primary
    End point timeframe
    Baseline (Week 0) and Week 40
    End point values
    Tralokinumab Placebo
    Number of subjects analysed
    70
    70
    Units: Percent change from baseline
        least squares mean (standard error)
    -37.62 ± 4.98
    -29.85 ± 4.98
    Statistical analysis title
    Percent change from baseline in OCS dose
    Statistical analysis description
    Tralokinumab vs placebo.
    Comparison groups
    Tralokinumab v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    [1]
    P-value
    = 0.271
    Method
    ANCOVA
    Parameter type
    LS Mean difference
    Point estimate
    -7.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -21.7
         upper limit
    6.15
    Notes
    [1] - The null hypothesis was that the average percentage change in OCS dose on tralokinumab was equal to the average percentage change in OCS dose on placebo. The analysis of covariance (ANCOVA) model utilised a sandwich estimator for the variance. The model included treatment group as a fixed effect and baseline OCS dose as a continuous covariate. No interaction terms were included in the model. All group comparisons from the ANCOVA model were based on Type III sums of squares.

    Secondary: The number of patients with final daily average OCS dose ≤5 mg at Week 40.

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    End point title
    The number of patients with final daily average OCS dose ≤5 mg at Week 40.
    End point description
    The 40-week treatment period consisted of 3 phases: an induction phase (Week 0 to Week 12) where patients remained on their optimised OCS dose; an OCS reduction phase (Week 12 to Week 32) where OCS dose reduction could have started at Week 12 with the possibility of dose titration every 4 weeks to reach the lowest possible OCS dose; and a maintenance phase (Week 32 to Week 40) where patients remained on the OCS dose reached at Week 32 to demonstrate asthma control was maintained after achieving the lowest OCS dose. The number of patients with a final daily average OCS dose ≤5.0 mg is presented for the FAS, comprising all randomised patients who received at least one dose of study treatment. The average OCS dose was defined as {(Final daily average dose - baseline daily average dose)/baseline daily average dose}*100%.
    End point type
    Secondary
    End point timeframe
    At Week 40
    End point values
    Tralokinumab Placebo
    Number of subjects analysed
    70
    70
    Units: Participants
    32
    28
    Statistical analysis title
    Number of patients with OCS dose ≤5 mg
    Statistical analysis description
    Tralokinumab vs placebo.
    Comparison groups
    Tralokinumab v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    [2]
    P-value
    = 0.442
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.65
         upper limit
    2.73
    Notes
    [2] - The model included treatment group as a fixed effect and baseline OCS dose as a continuous covariate.

    Secondary: The number of patients with ≥50% reduction in final average daily OCS dose at Week 40.

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    End point title
    The number of patients with ≥50% reduction in final average daily OCS dose at Week 40.
    End point description
    The 40-week treatment period consisted of 3 phases: an induction phase (Week 0 to Week 12) where patients remained on their optimised OCS dose; an OCS reduction phase (Week 12 to Week 32) where OCS dose reduction could have started at Week 12 with the possibility of dose titration every 4 weeks to reach the lowest possible OCS dose; and a maintenance phase (Week 32 to Week 40) where patients remained on the OCS dose reached at Week 32 to demonstrate asthma control was maintained after achieving the lowest OCS dose. The number of patients with ≥50% reduction in average daily OCS dose is presented for the FAS, comprising all randomised patients who received at least one dose of study treatment. The average OCS dose was defined as {(Final daily average dose - baseline daily average dose)/baseline daily average dose}*100%. If this resulted in a value of -50% or less (more negative), that patient was classified as having at least a 50% reduction in final daily average OCS dose.
    End point type
    Secondary
    End point timeframe
    At Week 40
    End point values
    Tralokinumab Placebo
    Number of subjects analysed
    70
    70
    Units: Participants
    31
    26
    Statistical analysis title
    Number of patients with ≥50% reduction in OCS dose
    Statistical analysis description
    Tralokinumab vs placebo.
    Comparison groups
    Tralokinumab v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    [3]
    P-value
    = 0.356
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.38
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.7
         upper limit
    2.74
    Notes
    [3] - The model included treatment group as a fixed effect and baseline OCS dose as a continuous covariate.

    Secondary: Annual asthma exacerbation rate (AAER) up to Week 40.

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    End point title
    Annual asthma exacerbation rate (AAER) up to Week 40.
    End point description
    Asthma exacerbation was defined as a worsening of asthma that led to any of the following: • Use of systemic corticosteroids for at least 3 days; a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids. • An emergency room (ER) or urgent care (UC) visit (defined as evaluation and treatment for <24 hours in an ER or UC centre) due to asthma that required systemic corticosteroids (see above). • An inpatient hospitalisation (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours) due to asthma. AAER = number of exacerbations*365.25 / (follow-up date - date of randomisation + 1) (where maximum follow-up for a patient was 40 weeks). AAER in tralokinumab group was compared with AAER in placebo group up to Week 40 using a negative binomial model. AAER is presented for the FAS, comprising all randomised patients who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0) up to Week 40
    End point values
    Tralokinumab Placebo
    Number of subjects analysed
    70
    70
    Units: Events/year
        number (confidence interval 95%)
    1.84 (1.43 to 2.36)
    2.31 (1.83 to 2.92)
    Statistical analysis title
    AAER
    Statistical analysis description
    Tralokinumab vs placebo.
    Comparison groups
    Tralokinumab v Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    [4]
    P-value
    = 0.186
    Method
    Negative binomial
    Parameter type
    Rate Ratio
    Point estimate
    0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.57
         upper limit
    1.12
    Notes
    [4] - Treatment group, OCS dose at baseline, and number of exacerbations in the previous year are included in the model as covariates.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    40 weeks.
    Adverse event reporting additional description
    Data is reported for adverse events with an onset date ≥ the first day of study treatment and ≤ (the last day of study treatment + 2 weeks). Patient population was the safety analysis set which included all patients who received at least one dose of study treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo was administered by SC injection over a 40-week treatment period.

    Reporting group title
    Tralo 300 mg Q2W
    Reporting group description
    Tralokinumab 300 mg administered by SC injection Q2W over a 40-week treatment period.

    Serious adverse events
    Placebo Tralo 300 mg Q2W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 70 (22.86%)
    9 / 70 (12.86%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Hand fracture
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Pulmonary function test abnormal
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer female
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         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
    Asthma
         subjects affected / exposed
    8 / 70 (11.43%)
    5 / 70 (7.14%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal prolapse
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 70 (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
    1 / 70 (1.43%)
    0 / 70 (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
    Tendonitis
         subjects affected / exposed
    0 / 70 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 70 (1.43%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 70 (1.43%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo Tralo 300 mg Q2W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    44 / 70 (62.86%)
    55 / 70 (78.57%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 70 (2.86%)
    4 / 70 (5.71%)
         occurrences all number
    2
    4
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    9 / 70 (12.86%)
    3 / 70 (4.29%)
         occurrences all number
    10
    4
    Cough
         subjects affected / exposed
    1 / 70 (1.43%)
    4 / 70 (5.71%)
         occurrences all number
    1
    4
    Dyspnoea
         subjects affected / exposed
    2 / 70 (2.86%)
    4 / 70 (5.71%)
         occurrences all number
    2
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 70 (15.71%)
    14 / 70 (20.00%)
         occurrences all number
    15
    33
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    5 / 70 (7.14%)
    3 / 70 (4.29%)
         occurrences all number
    6
    3
    Injection site pruritus
         subjects affected / exposed
    0 / 70 (0.00%)
    5 / 70 (7.14%)
         occurrences all number
    0
    6
    Injection site pain
         subjects affected / exposed
    2 / 70 (2.86%)
    6 / 70 (8.57%)
         occurrences all number
    2
    12
    Injection site erythema
         subjects affected / exposed
    0 / 70 (0.00%)
    6 / 70 (8.57%)
         occurrences all number
    0
    13
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 70 (2.86%)
    7 / 70 (10.00%)
         occurrences all number
    2
    7
    Arthralgia
         subjects affected / exposed
    6 / 70 (8.57%)
    2 / 70 (2.86%)
         occurrences all number
    7
    3
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    16 / 70 (22.86%)
    11 / 70 (15.71%)
         occurrences all number
    20
    12
    Sinusitis
         subjects affected / exposed
    4 / 70 (5.71%)
    5 / 70 (7.14%)
         occurrences all number
    4
    7
    Oral candidiasis
         subjects affected / exposed
    4 / 70 (5.71%)
    2 / 70 (2.86%)
         occurrences all number
    4
    2
    Urinary tract infection
         subjects affected / exposed
    4 / 70 (5.71%)
    2 / 70 (2.86%)
         occurrences all number
    4
    2
    Viral upper respiratory tract infection
         subjects affected / exposed
    10 / 70 (14.29%)
    25 / 70 (35.71%)
         occurrences all number
    12
    33

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 May 2015
    - Text clarified to state that only adult patients (and not adolescent) were to be stratified by the baseline OCS dose. - The OCS dose reduction categories were revised to increase the granularity of the categories. The timing of the OCS dose reduction was also clarified. - The adjudication committee responsibilities were updated to include review of cardiovascular, cerebrovascular and malignancy adverse events occurring after randomisation since patients with severe asthma have been described to suffer from an increased risk of co- morbid illnesses. - Inclusion criteria were revised to clarify that every other day dosing of OCS was allowed and to provide clarification on the administration of theophylline relative to lung function measurements. - Procedures for discontinuation of a patient from study treatment were clarified to allow a patient with an asthma-related event requiring non-invasive ventilation to continue receiving treatment. - The run-in reversibility procedure was clarified.
    07 Aug 2015
    - The OCS dose titration details were revised to clarify that for patients entering the OCS dose optimisation period, dose titration had to begin at Visit 2, and to clarify that the minimum maintenance OCS dose required applied to patients on a dose between 15 to 30 mg/day.
    22 Feb 2016
    - Inclusion criteria were revised to allow patients with a pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) <80% (<90% for patients 12 to 17 years of age) of their predicted normal value to be included into the study, and to remove the requirement of a post-BD reversibility in FEV1 being ≥200 mL. - Exclusion criteria were revised to clarify the time restrictions for receipt of any marketed or investigational biologic agents by study patients, and to clarify the time restrictions for receipt of live attenuated vaccines by study patients.
    02 Aug 2017
    - The possible primary populations for this study were clarified, based on the biomarker fractional exhaled nitric oxide concentrations, in light of the results from the pivotal study D2210C00007. - The primary objective was modified to clarify that this objective applies to the primary population. - The secondary objectives regarding the proportion of patients with prescribed OCS maintenance dose ≤5 mg at Week 40 and reduction of at least 50% of prescribed OCS dose at Week 40 were modified to clarify that each objective applies to the primary population. - The reduction of exacerbation rate was elevated from an exploratory objective to a secondary objective. - Removal of the term “at steady-state” regarding the serum trough concentration exploratory outcome variable for clarification purposes. - The Biomarker objective was modified to allow the implementation of the biomarker strategy that is being decided from the pivotal study D2210C00007. Consequently, the sample size rationale was also modified. - The PK analysis set description was updated. - Testing strategy for primary and key secondary variables was revised.

    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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