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    Clinical Trial Results:
    A randomised, double-blind, placebo-controlled, parallel-group, multi-centre, phase 3 trial investigating the efficacy, safety, and tolerability of tralokinumab administered in combination with topical corticosteroids to adult subjects with severe atopic dermatitis who are not adequately controlled with or have contraindications to oral cyclosporine A

    Summary
    EudraCT number
    		 2018-000747-76
    Trial protocol
    		 FR   DE   BE   GB   ES   CZ  
    Global end of trial date
    28 Sep 2020

    Results information
    Results version number
    		 v2(current)
    This version publication date
    26 May 2023
    First version publication date
    13 Oct 2021
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Data added.

    Trial information

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    Trial identification
    Sponsor protocol code
    LP0162-1346
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03761537
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Leo Pharma A/S
    Sponsor organisation address
    Industriparken 55, Ballerup, Denmark, 2750
    Public contact
    Clinical Disclosure Specialist, Leo Pharma A/S, 0045 44945888, disclosure@leo-pharma.com
    Scientific contact
    Clinical Disclosure Specialist, Leo Pharma A/S, 0045 44945888, disclosure@leo-pharma.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
    04 Mar 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Apr 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Sep 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that tralokinumab in combination with topical corticosteroids (TCS) is superior to placebo in combination with TCS in treating severe Atopic Dermatitis (AD) in subjects who are not adequately controlled with or have contraindications to oral cyclosporine A (CSA).
    Protection of trial subjects
    Subjects were asked to consent that their personal data were recorded, collected, processed and could be transferred to EU and non-EU countries in accordance with any national legislation regulating privacy and data protection
    Background therapy
    		 All subjects were required to use an emollient twice daily (or more as needed) for at least 14 days before randomisation and to continue this treatment throughout the trial until the end of the safety follow-up period.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Dec 2018
    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
    Belgium: 52
    Country: Number of subjects enrolled
    France: 19
    Country: Number of subjects enrolled
    Germany: 40
    Country: Number of subjects enrolled
    Poland: 77
    Country: Number of subjects enrolled
    Spain: 49
    Country: Number of subjects enrolled
    Czechia: 26
    Country: Number of subjects enrolled
    United Kingdom: 14
    Worldwide total number of subjects
    277
    EEA total number of subjects
    263
    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)
    265
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 After the participant gave informed consent, they went through a 2- to 6-week screening period. Eligibility was assessed at the (first) screening visit and on Day 0 (hereinafter “baseline”) prior to randomisation.

    Period 1
    Period 1 title
    Treatment period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Subjects were randomised to treatment at Day 0 (Visit 3, baseline). This was a double-blinded trial where tralokinumab and placebo were visually distinct from each other and not matched for viscosity. They were therefore handled and administered by a qualified unblinded health care professional (trained site staff) at the site who was not involved in the management of trial subjects and who did not perform any of the assessments.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tralokinumab + TCS
    Arm description
    		 Subjects in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tralokinumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received a loading dose of 600 mg tralokinumab at Day 0 (Visit 3, baseline) followed by a dose of 300 mg tralokinumab every second week (Q2W) from Week 2. The last administration of IMP occurred at Week 24. The injections were administered in the subcutaneous tissue of the upper arm, anterior thigh, or abdomen.

    Arm title
    		 Placebo + TCS
    Arm description
    		 Subjects in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received a loading dose of placebo at Day 0 (Visit 3, baseline) followed by a dose of placebo every second week (Q2W) from Week 2. The last administration of IMP occurred at Week 24. The injections were administered in the subcutaneous tissue of the upper arm, anterior thigh, or abdomen.

    Number of subjects in period 1
    		Tralokinumab + TCS Placebo + TCS
    Started
    140
    137
    Completed
    125
    120
    Not completed
    15
    17
         Permanently discontinued IMP
    13
    17
         Subject not dosed
    2
    -
    Period 2
    Period 2 title
    Safety follow-up period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    No treatment was administered to the subjects during the safety follow-up period and therefore no randomisation took place. However, double blinding was maintained throughout the period.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Safety follow-up, tralokinumab
    Arm description
    		 Subjects who spent any amount of time in the safety follow-up period, independently of the treatment(s) received before. No treatment was administered to the subjects during this period. Eligible subjects who completed treatment could transfer to a long-term extension trial (conducted under a separate protocol) at any time during the safety follow-up period.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Safety follow-up, placebo
    Arm description
    		 Subjects who spent any amount of time in the safety follow-up period, independently of the treatment(s) received before. No treatment was administered to the subjects during this period. Eligible subjects who completed treatment could transfer to a long-term extension trial (conducted under a separate protocol) at any time during the safety follow-up period
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2 [1]
    		Safety follow-up, tralokinumab Safety follow-up, placebo
    Started
    75
    83
    Completed
    9
    17
    Not completed
    66
    66
         Withdrew from trial
    1
    6
         COVID-19
    1
    3
         Other
    1
    1
         Lost to follow-up
    -
    1
         Transferred to other trial
    63
    55
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: A proportion of subjects completing the treatment period were immediately transferred to an extension trial (ECZTEND trial) and thus, did not attend the safety follow-up period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tralokinumab + TCS
    Reporting group description
    		 Subjects in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed.

    Reporting group title
    Placebo + TCS
    Reporting group description
    		 Subjects in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed.

    Reporting group values
    		 Tralokinumab + TCS Placebo + TCS Total
    Number of subjects
    		 140 137 277
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 134 131 265
        From 65-84 years
    		 6 6 12
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 33.08 (25.5 to 47.0) 34.0 (26.0 to 45.0) -
    Gender categorical
    Units: Subjects
        Female
    		 58 54 112
        Male
    		 82 83 165
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 6 4 10
        Not hispanic or latino
    		 134 133 267
        Unknown or not reported
    		 0 0 0
    Race
    Units: Subjects
        Asian
    		 0 1 1
        Native Hawaiian or other pacific islander
    		 1 0 1
        Black or african american
    		 0 1 1
        White
    		 137 135 272
        Unknown or not reported
    		 2 0 2
    Age at onset of atopic dermatitis
    Units: Years
        median (inter-quartile range (Q1-Q3))
    		 2.5 (1.0 to 12.5) 3.0 (1.0 to 17.0) -
    Body surface area with atopic dermatitis
    Units: Percentage affected
        median (inter-quartile range (Q1-Q3))
    		 52.0 (36.5 to 70.0) 52.0 (35.0 to 70.0) -
    Eczema area and severity index (EASI)
    Measure Description: EASI is used to evaluate the extent and severity of atopic dermatitis. It is a composite score ranging from 0 to 72 with a higher score indicating a more extensive and/or severe condition. Measure Analysis Population Description: The number of participants analysed is different from the number of participants randomised due to missing data. Tralokinumab + TCS = 138 participants; Placebo + TCS = 137 participants.
    Units: Units on a scale
        median (inter-quartile range (Q1-Q3))
    		 28.6 (22.4 to 38.0) 29.1 (22.8 to 40.15) -
    Duration of atopic dermatitis
    Units: Years
        median (inter-quartile range (Q1-Q3))
    		 26.0 (18.0 to 35.0) 25.0 (17.0 to 34.0) -
    Scoring of Atopic Dermatitis
    Measure Description: SCORAD is used to evaluate the extent and severity of atopic dermatitis as well as subjective symptoms. The score ranges from 0 to 103 with a higher score indicating a more extensive and/or severe condition. Measure Analysis Population Description: The number of participants analysed is different from the number of participants randomised due to missing data. Tralokinumab + TCS = 138 participants; Placebo + TCS = 137 participants.
    Units: Units on a scale
        median (inter-quartile range (Q1-Q3))
    		 69.2 (61.5 to 76.5) 68.9 (61.2 to 81.0) -
    Dermatology Life Quality Index (DLQI)
    Measure Description: DLQI is used by the participant to evaluate the impact of their condition on 10 different aspects of health-related quality of life (HRQoL) over the last week. Each item is scored on a 4-point Likert scale ranging from 0 (not at all/not relevant) to 3 (very much). The total score which is the sum of the 10 items ranges from 0 to 30, with a higher score indicating a poorer HRQoL. The number of participants analysed is different from the number of participants randomised due to missing data. Tralokinumab + TCS = 137 subjects; Placebo + TCS = 134 subjects
    Units: Units on a scale
        median (inter-quartile range (Q1-Q3))
    		 16 (11 to 21) 16 (11 to 21) -
    Worst Daily Pruritis numeric rating scale (NRS), weekly average
    Measure Description: Worst Daily Pruritus NRS is used by the participant to evaluate their worst itch severity over the past 24 hours. The score ranges from 0 ('no itch') to 10 ('worst itch imaginable'). Measure Analysis Population Description: The number of participants analysed is different from the number of participants randomised due to missing data. Tralokinumab + TCS = 137 subjects; Placebo + TCS = 136 subjects
    Units: Units on a scale
        median (inter-quartile range (Q1-Q3))
    		 7.43 (6.43 to 8.29) 7.50 (6.59 to 8.37) -

    End points

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    End points reporting groups
    Reporting group title
    Tralokinumab + TCS
    Reporting group description
    		 Subjects in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed.

    Reporting group title
    Placebo + TCS
    Reporting group description
    		 Subjects in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed.
    Reporting group title
    Safety follow-up, tralokinumab
    Reporting group description
    		 Subjects who spent any amount of time in the safety follow-up period, independently of the treatment(s) received before. No treatment was administered to the subjects during this period. Eligible subjects who completed treatment could transfer to a long-term extension trial (conducted under a separate protocol) at any time during the safety follow-up period.

    Reporting group title
    Safety follow-up, placebo
    Reporting group description
    		 Subjects who spent any amount of time in the safety follow-up period, independently of the treatment(s) received before. No treatment was administered to the subjects during this period. Eligible subjects who completed treatment could transfer to a long-term extension trial (conducted under a separate protocol) at any time during the safety follow-up period

    Primary: Subjects achieving at least 75% reduction in Eczema Area and Severity Index (EASI75) from Week 0 to Week 16

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    End point title
    		 Subjects achieving at least 75% reduction in Eczema Area and Severity Index (EASI75) from Week 0 to Week 16
    End point description
    Subjects who achieved at least 75% reduction in EASI at Week 16 were defined as responders. EASI is used to evaluate the extent and severity of atopic dermatitis. It is a composite score ranging from 0 to 72 with a higher score indicating a more extensive and/or severe condition. Results of the primary analysis of the primary estimand are reported below. The other analyses supported these results. The analysis was based on the full analysis set (FAS). Of the 277 subjects randomised to treatment, 275 were treated. Therefore, the FAS consisted of 275 subjects.
    End point type
    Primary
    End point timeframe
    Week 0 to Week 16
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    138
    137
    Units: Percentage of responders
        number (not applicable)
    64.2
    50.5
    Statistical analysis title
    		 Tralokinumab+TCS vs placebo+TCS
    Statistical analysis description
    Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
    Comparison groups
    Tralokinumab + TCS v Placebo + TCS
    Number of subjects included in analysis
    275
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.018 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    14.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.5
         upper limit
    		 25.7
    Notes
    [1] - The null hypothesis of no difference in response rates between tralokinumab +TCS and placebo+TCS was tested against the 2-sided alternative that there was a difference.
    [2] - The significance level is set to 0.05 (5%). The analysis was conducted using Cochran-Mantel-Haenszel test stratified by prior CSA use and baseline disease severity.

    Secondary: Reduction of Worst Daily Pruritus (NRS) (Weekly Average) of at least 4 from Week 0 to Week 16

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    End point title
    		 Reduction of Worst Daily Pruritus (NRS) (Weekly Average) of at least 4 from Week 0 to Week 16
    End point description
    Subjects will assess their worst itch severity over the past 24 hours using an 11-point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. Results of the primary analysis of the primary estimand are reported below. The other analyses supported these results. The analysis was based on subjects in the full analysis set with a Worst Daily Pruritus NRS (weekly average) of at least 4 at baseline (Week 0). Subjects meeting the endpoint were defined as responders.
    End point type
    Secondary
    End point timeframe
    Week 0 to Week 16
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    134
    135
    Units: Percentage of responders
        number (not applicable)
    45.5
    35.6
    Statistical analysis title
    		 Tralokinumab+TCS vs placebo+TCS
    Statistical analysis description
    Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
    Comparison groups
    Tralokinumab + TCS v Placebo + TCS
    Number of subjects included in analysis
    269
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.106 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    9.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2
         upper limit
    		 21.4
    Notes
    [3] - The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
    [4] - The significance level is set to 0.05 (5%). The analysis was conducted using Cochran-Mantel-Haenszel test stratified by prior CSA use and baseline disease severity.

    Secondary: Change in Scoring Atopic Dermatitis (SCORAD) from Week 0 to Week 16

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    End point title
    		 Change in Scoring Atopic Dermatitis (SCORAD) from Week 0 to Week 16
    End point description
    SCORAD is used to evaluate the extent and severity of atopic dermatitis as well as subjective symptoms. The score ranges from 0 to 103 with a higher score indicating a more extensive and/or severe condition. Results of the primary analysis of the primary estimand are reported below. The other analyses supported these results. The analysis was based on the full analysis set.
    End point type
    Secondary
    End point timeframe
    Week 0 to Week 16
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    138
    137
    Units: Units on a scale
        arithmetic mean (standard error)
    -42.7 ± 1.6
    -34.1 ± 1.6
    Statistical analysis title
    		 Tralokinumab+TCS vs placebo+TCS
    Statistical analysis description
    Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic, were not included in the analysis.
    Comparison groups
    Tralokinumab + TCS v Placebo + TCS
    Number of subjects included in analysis
    275
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 < 0.001 [6]
    Method
    		 Repeated measurements model
    Parameter type
    		 Difference
    Point estimate
    -8.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13
         upper limit
    		 -4.2
    Notes
    [5] - The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
    [6] - The significance level is set to 0.05 (5%).

    Secondary: Change in Dermatology Life Quality Index (DLQI) score from Week 0 to Week 16

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    End point title
    		 Change in Dermatology Life Quality Index (DLQI) score from Week 0 to Week 16
    End point description
    DLQI is used by the subject to evaluate the impact of their condition on 10 different aspects of health-related quality of life (HRQoL) over the last week. Each item is scored on a 4-point Likert scale ranging from 0 (not at all/not relevant) to 3 (very much). The total score which is the sum of the 10 items ranges from 0 to 30, with a higher score indicating a poorer HRQoL. Results of the primary analysis of the primary estimand are reported below. The other analyses supported these results. The analysis was based on the full analysis set.
    End point type
    Secondary
    End point timeframe
    Week 0 to Week 16
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    137
    134
    Units: Units on a scale
        arithmetic mean (standard error)
    -11.2 ± 0.4
    -9.6 ± 0.4
    Statistical analysis title
    		 Tralokinumab+TCS vs placebo+TCS
    Statistical analysis description
    Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic were not included in the analysis.
    Comparison groups
    Tralokinumab + TCS v Placebo + TCS
    Number of subjects included in analysis
    271
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 = 0.009 [8]
    Method
    		 Repeated measurements model
    Parameter type
    		 Difference
    Point estimate
    -1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.6
         upper limit
    		 -0.4
    Notes
    [7] - The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
    [8] - The significance level is set to 0.05 (5%).

    Secondary: Subjects with Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) at Week 16

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    End point title
    		 Subjects with Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) at Week 16
    End point description
    IGA is used to evaluate the severity of atopic dermatitis. It is a 5-point score ranging from 0 (clear) to 4 (severe). Subjects who achieved IGA 0 or 1 at Week 16 were defined as responders. Results of the primary analysis of the primary estimand are reported below. The other analyses supported these results. The analysis was based on the full analysis set.
    End point type
    Secondary
    End point timeframe
    At Week 16
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    138
    137
    Units: Percentage of responders
        number (not applicable)
    40.9
    26.0
    Statistical analysis title
    		 Tralokinumab+TCS vs placebo+TCS
    Statistical analysis description
    Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
    Comparison groups
    Tralokinumab + TCS v Placebo + TCS
    Number of subjects included in analysis
    275
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.005 [10]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    15.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.8
         upper limit
    		 26.3
    Notes
    [9] - The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
    [10] - The significance level is set to 0.05 (5%). The analysis was conducted using Cochran-Mantel-Haenszel test stratified by prior CSA use and baseline disease severity.

    Secondary: Subjects achieving at least 75% reduction in Eczema Area and Severity Index (EASI75) from Week 0 to Week 26

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    End point title
    		 Subjects achieving at least 75% reduction in Eczema Area and Severity Index (EASI75) from Week 0 to Week 26
    End point description
    EASI (Eczema Area and Severity Index) is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition. Subjects who achieved at least 75% reduction in EASI at Week 26 were defined as responders. Results of the primary analysis of the primary estimand are reported below. The other analyses supported these results. The analysis was based on the full analysis set.
    End point type
    Secondary
    End point timeframe
    Week 0 to Week 26
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    138
    137
    Units: Percentage of responders
        number (not applicable)
    68.8
    55.3
    Statistical analysis title
    		 Tralokinumab+TCS vs placebo+TCS
    Statistical analysis description
    Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
    Comparison groups
    Tralokinumab + TCS v Placebo + TCS
    Number of subjects included in analysis
    275
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 = 0.014 [12]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    14.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.9
         upper limit
    		 25.3
    Notes
    [11] - The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
    [12] - The significance level is set to 0.05 (5%). The analysis was conducted using Cochran-Mantel-Haenszel test stratified by prior CSA use and baseline disease severity.

    Secondary: Reduction of Worst Daily Pruritus NRS (Weekly Average) of at least 4 from Week 0 to Week 26

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    End point title
    		 Reduction of Worst Daily Pruritus NRS (Weekly Average) of at least 4 from Week 0 to Week 26
    End point description
    Subjects will assess their worst itch severity over the past 24 hours using an 11-point numeric rating scale ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. Subjects meeting the endpoint were defined as responders. Results of the primary analysis of the primary estimand are reported below. The other analyses supported these results. The analysis was based on subjects in the full analysis set with a Worst Daily Pruritus NRS (weekly average) of at least 4 at baseline (Week 0).
    End point type
    Secondary
    End point timeframe
    Week 0 to Week 26
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    134
    135
    Units: Percentage of responders
        number (not applicable)
    47.2
    39.7
    Statistical analysis title
    		 Tralokinumab+TCS vs placebo+TCS
    Statistical analysis description
    Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
    Comparison groups
    Tralokinumab + TCS v Placebo + TCS
    Number of subjects included in analysis
    269
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.228 [14]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    7.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 19.2
    Notes
    [13] - The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
    [14] - The significance level is set to 0.05 (5%). The analysis was conducted using Cochran-Mantel-Haenszel test stratified by prior CSA use and baseline disease severity.

    Secondary: Change in Scoring Atopic Dermatitis (SCORAD) from Week 0 to Week 26

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    End point title
    		 Change in Scoring Atopic Dermatitis (SCORAD) from Week 0 to Week 26
    End point description
    SCORAD is used to evaluate the extent and severity of atopic dermatitis as well as subjective symptoms. The score ranges from 0 to 103 with a higher score indicating a more extensive and/or severe condition. Results of the primary analysis of the primary estimand are reported below. The other analyses supported these results. The analysis was based on the full analysis set.
    End point type
    Secondary
    End point timeframe
    Week 0 to Week 26
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    138
    137
    Units: Units on a scale
        arithmetic mean (standard error)
    -46.3 ± 1.5
    -37.3 ± 1.6
    Statistical analysis title
    		 Tralokinumab+TCS vs placebo+TCS
    Statistical analysis description
    Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic will not be included in the analysis.
    Comparison groups
    Tralokinumab + TCS v Placebo + TCS
    Number of subjects included in analysis
    275
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    P-value
    		 < 0.001 [16]
    Method
    		 Repeated measurements model
    Parameter type
    		 Difference
    Point estimate
    -8.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.2
         upper limit
    		 -4.6
    Notes
    [15] - The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
    [16] - The significance level is set to 0.05 (5%).

    Secondary: Change in Dermatology Life Quality Index (DLQI) score from Week 0 to Week 26

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    End point title
    		 Change in Dermatology Life Quality Index (DLQI) score from Week 0 to Week 26
    End point description
    DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their health-related quality of life (HRQoL) over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4-point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor HRQoL. Results of the primary analysis of the primary estimand are reported below. The other analyses supported these results. The analysis was based on the full analysis set.
    End point type
    Secondary
    End point timeframe
    Week 0 to Week 26
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    137
    134
    Units: Units on a scale
        arithmetic mean (standard error)
    -11.5 ± 0.4
    -9.9 ± 0.4
    Statistical analysis title
    		 Tralokinumab+TCS vs placebo+TCS
    Statistical analysis description
    Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic will not be included in the analysis.
    Comparison groups
    Tralokinumab + TCS v Placebo + TCS
    Number of subjects included in analysis
    271
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    P-value
    		 = 0.005 [18]
    Method
    		 Repeated measurements model
    Parameter type
    		 Difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 -0.5
    Notes
    [17] - The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
    [18] - The significance level is set to 0.05 (5%).

    Secondary: Subjects with Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) at Week 26

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    End point title
    		 Subjects with Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) at Week 26
    End point description
    IGA is used to evaluate the severity of atopic dermatitis. It is a 5-point score ranging from 0 (clear) to 4 (severe). Subjects who achieved IGA 0 or 1 at Week 26 were defined as responders. Results of the primary analysis of the primary estimand are reported below. The other analyses supported these results. The analysis was based on the full analysis set.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    138
    137
    Units: Percentage of responders
        number (not applicable)
    47.0
    33.4
    Statistical analysis title
    		 Tralokinumab+TCS vs placebo+TCS
    Statistical analysis description
    Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.
    Comparison groups
    Tralokinumab + TCS v Placebo + TCS
    Number of subjects included in analysis
    275
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    P-value
    		 = 0.014 [20]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    14.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.9
         upper limit
    		 25.6
    Notes
    [19] - The null hypothesis of no difference between Tralokinumab+TCS and placebo+TCS was tested at a 5% significance level against the 2-sided alternative that there was a difference.
    [20] - The significance level is set to 0.05 (5%). The analysis was conducted using Cochran-Mantel-Haenszel test stratified by prior CSA use and baseline disease severity.

    Secondary: Frequency of anti-drug antibodies (ADA)

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    End point title
    		 Frequency of anti-drug antibodies (ADA)
    End point description
    End point type
    Secondary
    End point timeframe
    From Week 0 to Week 40
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    138
    137
    Units: Count of Participants
        Positive
    2
    3
        Negative
    134
    133
        Perishing
    1
    1
        No post-baseline ADA assessment
    1
    0
    No statistical analyses for this end point

    Secondary: Number of adverse events from Week 0 to Week 40

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    End point title
    		 Number of adverse events from Week 0 to Week 40
    End point description
    All adverse events are presented below under Adverse Events.
    End point type
    Secondary
    End point timeframe
    Week 0 to Week 40
    End point values
    		 Tralokinumab + TCS Placebo + TCS
    Number of subjects analysed
    138
    137
    Units: Number of adverse events
    389
    435
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All adverse events were collected from the time of signed informed consent form to the end of the trial (safety follow-up visit at Week 40).
    Adverse event reporting additional description
    The analysis was conducted based on the safety analysis set which consisted of subjects exposed to at least 1 dose of investigational medicinal product.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Treatment period: Tralokinumab + TCS
    Reporting group description
    		 Subjects in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed. Subjects received a loading dose of 600 mg tralokinumab at Week 0 followed by a dose of 300 mg tralokinumab every second week (Q2W) from Week 2. The last administration of IMP occurred at Week 24.

    Reporting group title
    Treatment period: Placebo + TCS
    Reporting group description
    		 Subjects in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed. Subjects were administered placebo at Week 0 followed by administration of placebo Q2W from Week 2. The last administration of IMP occurred at Week 24.

    Reporting group title
    Safety follow-up period: Tralokinumab
    Reporting group description
    		 Subjects who spent any amount of time in the safety follow-up period, independently of the treatment(s) received before. No treatment was administered to the subjects during this period. Eligible subjects who completed treatment could transfer to a long-term extension trial (conducted under a separate protocol) at any any time during the safety follow-up period.

    Reporting group title
    Safety follow-up period: Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 Treatment period: Tralokinumab + TCS Treatment period: Placebo + TCS Safety follow-up period: Tralokinumab Safety follow-up period: Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 138 (0.72%)
    5 / 137 (3.65%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 138 (0.00%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Peripheral nerve injury
         subjects affected / exposed
    0 / 138 (0.00%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 138 (0.00%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 138 (0.00%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 138 (0.00%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 138 (0.00%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis atopic
         subjects affected / exposed
    0 / 138 (0.00%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depressed mood
         subjects affected / exposed
    0 / 138 (0.00%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 138 (0.00%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 138 (0.72%)
    0 / 137 (0.00%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 138 (0.00%)
    0 / 137 (0.00%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Treatment period: Tralokinumab + TCS Treatment period: Placebo + TCS Safety follow-up period: Tralokinumab Safety follow-up period: Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    107 / 138 (77.54%)
    108 / 137 (78.83%)
    4 / 75 (5.33%)
    6 / 83 (7.23%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 138 (0.00%)
    0 / 137 (0.00%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         occurrences all number
    0
    0
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 138 (2.17%)
    7 / 137 (5.11%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    3
    7
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 138 (2.90%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    4
    3
    0
    0
    Influenza like illness
         subjects affected / exposed
    3 / 138 (2.17%)
    0 / 137 (0.00%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Injection site pain
         subjects affected / exposed
    4 / 138 (2.90%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    5
    3
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    4 / 138 (2.90%)
    8 / 137 (5.84%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    5
    9
    0
    0
    Cough
         subjects affected / exposed
    4 / 138 (2.90%)
    7 / 137 (5.11%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    5
    7
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 138 (0.72%)
    8 / 137 (5.84%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    1
    8
    0
    0
    Injury, poisoning and procedural complications
    Skin abrasion
         subjects affected / exposed
    3 / 138 (2.17%)
    0 / 137 (0.00%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    21 / 138 (15.22%)
    13 / 137 (9.49%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    25
    18
    0
    0
    Eye disorders
    Conjunctivitis allergic
         subjects affected / exposed
    6 / 138 (4.35%)
    5 / 137 (3.65%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    8
    5
    0
    0
    Dry eye
         subjects affected / exposed
    3 / 138 (2.17%)
    1 / 137 (0.73%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         occurrences all number
    3
    1
    0
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 138 (0.72%)
    5 / 137 (3.65%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    1
    8
    0
    0
    Dyspepsia
         subjects affected / exposed
    1 / 138 (0.72%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 138 (0.00%)
    0 / 137 (0.00%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         occurrences all number
    0
    0
    0
    1
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 138 (0.00%)
    0 / 137 (0.00%)
    1 / 75 (1.33%)
    0 / 83 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia areata
         subjects affected / exposed
    0 / 138 (0.00%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Dermatitis atopic
         subjects affected / exposed
    7 / 138 (5.07%)
    16 / 137 (11.68%)
    0 / 75 (0.00%)
    2 / 83 (2.41%)
         occurrences all number
    11
    26
    0
    2
    Diffuse alopecia
         subjects affected / exposed
    3 / 138 (2.17%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    3
    3
    0
    0
    Pruritus
         subjects affected / exposed
    6 / 138 (4.35%)
    5 / 137 (3.65%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    12
    6
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 138 (0.00%)
    0 / 137 (0.00%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         occurrences all number
    0
    0
    0
    1
    Renal and urinary disorders
    Renal cyst
         subjects affected / exposed
    0 / 138 (0.00%)
    0 / 137 (0.00%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         occurrences all number
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 138 (1.45%)
    3 / 137 (2.19%)
    1 / 75 (1.33%)
    0 / 83 (0.00%)
         occurrences all number
    2
    3
    1
    0
    Back pain
         subjects affected / exposed
    6 / 138 (4.35%)
    4 / 137 (2.92%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    6
    4
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 138 (0.00%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    0
    4
    0
    0
    Myalgia
         subjects affected / exposed
    4 / 138 (2.90%)
    2 / 137 (1.46%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    5
    2
    0
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    3 / 138 (2.17%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    4
    3
    0
    0
    Conjunctivitis
         subjects affected / exposed
    6 / 138 (4.35%)
    2 / 137 (1.46%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    6
    3
    0
    0
    Dermatitis infected
         subjects affected / exposed
    2 / 138 (1.45%)
    5 / 137 (3.65%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         occurrences all number
    2
    10
    0
    1
    Folliculitis
         subjects affected / exposed
    6 / 138 (4.35%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    6
    3
    0
    0
    Gastroenteritis
         subjects affected / exposed
    4 / 138 (2.90%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    4
    3
    0
    0
    Herpes simplex
         subjects affected / exposed
    1 / 138 (0.72%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    1
    4
    0
    0
    Influenza
         subjects affected / exposed
    3 / 138 (2.17%)
    4 / 137 (2.92%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    3
    4
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 138 (0.72%)
    6 / 137 (4.38%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    1
    6
    0
    0
    Oral herpes
         subjects affected / exposed
    5 / 138 (3.62%)
    6 / 137 (4.38%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    8
    6
    0
    0
    Pharyngitis
         subjects affected / exposed
    4 / 138 (2.90%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    4
    3
    0
    0
    Rhinitis
         subjects affected / exposed
    5 / 138 (3.62%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    6
    3
    0
    0
    Sinusitis
         subjects affected / exposed
    3 / 138 (2.17%)
    5 / 137 (3.65%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    4
    5
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 138 (0.00%)
    3 / 137 (2.19%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    10 / 138 (7.25%)
    10 / 137 (7.30%)
    0 / 75 (0.00%)
    0 / 83 (0.00%)
         occurrences all number
    12
    11
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    37 / 138 (26.81%)
    35 / 137 (25.55%)
    2 / 75 (2.67%)
    1 / 83 (1.20%)
         occurrences all number
    53
    46
    2
    1
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 138 (0.00%)
    2 / 137 (1.46%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         occurrences all number
    0
    2
    0
    1
    Pyelonephritis
         subjects affected / exposed
    0 / 138 (0.00%)
    0 / 137 (0.00%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         occurrences all number
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 138 (0.00%)
    0 / 137 (0.00%)
    0 / 75 (0.00%)
    1 / 83 (1.20%)
         occurrences all number
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Nov 2018
    The main reason for the amendment was to introduce the possibility for eligible subjects in selected countries to participate in a long-term extension trial (conducted under a separate protocol [LP0162-1337, ECZTEND]) without completing the safety follow-up period in the present trial.
    15 Jun 2020
    The main reason for the amendment was to modify the statistical analyses to account for an unusually high number of missing information due to COVID 19 pandemic in this trial. Statistical analysis was therefore revisited to ensure an unbiased evaluation of the treatment effect in the trial.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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