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    Clinical Trial Results:
    A Multicenter, Randomized, Double-Dummy, Double-Blind Study Evaluating Two Doses of Adalimumab versus Methotrexate (MTX) in Pediatric Subjects with Chronic Plaque Psoriasis (Ps)

    Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
    Summary
    EudraCT number
    2009-013072-52
    Trial protocol
    DE   BE   ES   CZ   HU   IT   Outside EU/EEA   NL  
    Global end of trial date
    03 Feb 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    18 May 2016
    First version publication date
    18 May 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    M04-717
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01251614
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AbbVie
    Sponsor organisation address
    1 North Waukegan Road, North Chicago, IL, United States, 60064
    Public contact
    Global Medical Information, AbbVie, 001 800-633-9110,
    Scientific contact
    David A Williams, AbbVie, david.a.williams@abbvie.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000366-PIP01-08
    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
    03 Feb 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Feb 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objectives of this study were to determine the safety and efficacy of 2 doses of adalimumab versus MTX in pediatric subjects with severe chronic plaque psoriasis, to determine the time to loss of disease control, the ability to regain response upon re-treatment, and to examine the pharmacokinetics (PK) and immunogenicity of adalimumab following subcutaneous (SC) administration in this subject population.
    Protection of trial subjects
    The investigator or his/her representative explained the nature of the study to the subject and the subject's parent/legal guardian, and answered all questions regarding this study. Paediatric subjects were included in all discussions in order to obtain verbal or written assent. Prior to any study-related screening procedures being performed on the subject, the informed consent statement was reviewed and signed and dated by the subject's parent/legal guardian and the person who administered the informed consent, and any other signatories according to local requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    14 Dec 2010
    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
    Chile: 5
    Country: Number of subjects enrolled
    Poland: 28
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Spain: 10
    Country: Number of subjects enrolled
    Belgium: 6
    Country: Number of subjects enrolled
    Czech Republic: 4
    Country: Number of subjects enrolled
    Germany: 11
    Country: Number of subjects enrolled
    Hungary: 8
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Mexico: 5
    Country: Number of subjects enrolled
    Switzerland: 4
    Country: Number of subjects enrolled
    Turkey: 3
    Country: Number of subjects enrolled
    Canada: 28
    Worldwide total number of subjects
    114
    EEA total number of subjects
    69
    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)
    42
    Adolescents (12-17 years)
    61
    Adults (18-64 years)
    11
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Subjects were to be children (from 4 to 11 years of age) and adolescents (from 12 through 17 years of age) with a clinical diagnosis of Ps for at least 6 months. Eligible subjects must have failed topical therapy and required systemic therapy to control their disease.

    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, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Methotrexate
    Arm description
    Subjects received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Subjects also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Subjects who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.
    Arm type
    Active comparator

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Methotrexate 0.1 mg/kg at Week 0 and up to 0.4 mg/kg per week (maximum dose of 25 mg/week) orally.

    Investigational medicinal product name
    Adalimumab Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    A single SC loading dose at Week 0 followed by eow dosing beginning at Week 1.

    Arm title
    Adalimumab 0.4 mg/kg
    Arm description
    In Period A subjects received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Humira
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Adalimumab by subcutaneous injection every other week (EOW)

    Investigational medicinal product name
    Methotrexate placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Orally once a week

    Arm title
    Adalimumab 0.8 mg/kg
    Arm description
    In Period A subjects received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Humira
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Adalimumab by subcutaneous injection every other week (EOW)

    Investigational medicinal product name
    Methotrexate placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Orally once a week

    Number of subjects in period 1
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Started
    37
    39
    38
    Entered Period B
    13 [1]
    18 [2]
    23 [3]
    Entered Period C
    8 [4]
    11 [5]
    19 [6]
    Entered Period D
    36
    36
    36
    Completed
    34
    26
    30
    Not completed
    3
    13
    8
         Adverse event
             1
             -
             1
         Almost total clearing of psoriatic lesions
             1
             -
             -
         Lack of efficacy
             1
             9
             4
         Pregnancy
             -
             -
             2
         Loss of disease control
             -
             1
             -
         Consent withdrawn by subject
             -
             2
             1
         Lost to follow-up
             -
             1
             -
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only subjects who were responders at Week 16 (Period A) entered the Treatment Withdrawal Phase (Period B)
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only subjects who were responders at Week 16 (Period A) entered the Treatment Withdrawal Phase (Period B)
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only subjects who were responders at Week 16 (Period A) entered the Treatment Withdrawal Phase (Period B)
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only subjects who experienced loss of disease control in Period B entered the Re-Treatment Phase (Period C)
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only subjects who experienced loss of disease control in Period B entered the Re-Treatment Phase (Period C)
    [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only subjects who experienced loss of disease control in Period B entered the Re-Treatment Phase (Period C)

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Methotrexate
    Reporting group description
    Subjects received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Subjects also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Subjects who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

    Reporting group title
    Adalimumab 0.4 mg/kg
    Reporting group description
    In Period A subjects received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow.

    Reporting group title
    Adalimumab 0.8 mg/kg
    Reporting group description
    In Period A subjects received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

    Reporting group values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg Total
    Number of subjects
    37 39 38 114
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    13.4 ± 3.49 12.6 ± 4.43 13 ± 3.29 -
    Gender categorical
    Units: Subjects
        Female
    26 18 21 65
        Male
    11 21 17 49

    End points

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    End points reporting groups
    Reporting group title
    Methotrexate
    Reporting group description
    Subjects received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Subjects also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Subjects who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

    Reporting group title
    Adalimumab 0.4 mg/kg
    Reporting group description
    In Period A subjects received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow.

    Reporting group title
    Adalimumab 0.8 mg/kg
    Reporting group description
    In Period A subjects received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets. Subjects who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Subjects who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Subjects who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Subjects who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Subjects who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

    Primary: Percentage of Subjects Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16

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    End point title
    Percentage of Subjects Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16
    End point description
    PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from Baseline in PASI score at Week 16. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Primary
    End point timeframe
    Baseline and Week 16
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
        number (not applicable)
    32.4
    43.6
    57.9
    Statistical analysis title
    Adalimumab 0.8 mg/kg versus MTX
    Comparison groups
    Methotrexate v Adalimumab 0.8 mg/kg
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    = 0.027
    Method
    Chi-squared
    Parameter type
    Difference
    Point estimate
    -25.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -47.2
         upper limit
    -3.7
    Notes
    [1] - The a priori defined order of the statistical hypotheses was as follows: 1. Superiority of adalimumab 0.8 mg/kg versus MTX, for the proportion of subjects achieving a ≥ PASI 75 response at Week 16. 2. Superiority of adalimumab 0.8 mg/kg versus MTX, for the proportion of subjects achieving a PGA cleared or minimal at Week 16. This order was adhered to for confirmatory testing, all statistical tests were to be done at a level of significance of 5% and the overall type I error was preserved.

    Primary: Percentage of Subjects Achieving a Physician’s Global Assessment of Disease Activity (PGA) of "Cleared" or "Minimal" (0 or 1) at Week 16

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    End point title
    Percentage of Subjects Achieving a Physician’s Global Assessment of Disease Activity (PGA) of "Cleared" or "Minimal" (0 or 1) at Week 16
    End point description
    The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared; 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal; 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild; 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate; 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked; 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe. The percentage of participants achieving a score of clear (0) or minimal (1) is reported. Non-responder imputation was used, the analysis was conducted in the ITT population.
    End point type
    Primary
    End point timeframe
    Week 16
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
        number (not applicable)
    40.5
    41
    60.5
    Statistical analysis title
    Adalimumab 0.8 mg/kg versus MTX
    Comparison groups
    Methotrexate v Adalimumab 0.8 mg/kg
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    = 0.083
    Method
    Chi-squared
    Parameter type
    Difference
    Point estimate
    -20
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -42.2
         upper limit
    2.2
    Notes
    [2] - The a priori defined order of the statistical hypotheses was as follows: 1. Superiority of adalimumab 0.8 mg/kg versus MTX, for the proportion of subjects achieving a ≥ PASI 75 response at Week 16. 2. Superiority of adalimumab 0.8 mg/kg versus MTX, for the proportion of subjects achieving a PGA cleared or minimal at Week 16. This order was adhered to for confirmatory testing, all statistical tests were to be done at a level of significance of 5% and the overall type I error was preserved.

    Secondary: Percentage of Subjects Who Achieved a PASI 90 Response at Week 16

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    End point title
    Percentage of Subjects Who Achieved a PASI 90 Response at Week 16
    End point description
    PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from Baseline in PASI score at Week 16. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
        number (not applicable)
    21.6
    30.8
    28.9
    Statistical analysis title
    Adalimumab 0.8 mg/kg versus MTX
    Comparison groups
    Adalimumab 0.8 mg/kg v Methotrexate
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    = 0.466
    Method
    Chi-squared
    Parameter type
    Difference
    Point estimate
    -7.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -26.9
         upper limit
    12.3
    Notes
    [3] - Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

    Secondary: Percentage of Subjects Who Achieved a PASI 100 Response at Week 16

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    End point title
    Percentage of Subjects Who Achieved a PASI 100 Response at Week 16
    End point description
    PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-100 response is the percentage of participants who achieved a 100% reduction (improvement) from Baseline in PASI score at Week 16. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
        number (not applicable)
    2.7
    10.3
    18.4
    Statistical analysis title
    Adalimumab 0.8 mg/kg versus MTX
    Comparison groups
    Adalimumab 0.8 mg/kg v Methotrexate
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    superiority [4]
    P-value
    = 0.056
    Method
    Fisher exact
    Parameter type
    Difference
    Point estimate
    -15.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -29.1
         upper limit
    -2.3
    Notes
    [4] - Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

    Secondary: Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Scores at Week 16

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    End point title
    Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Scores at Week 16
    End point description
    The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. Last observation carried forward (LOCF) imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    36
    38
    38
    Units: units on a scale
        arithmetic mean (standard deviation)
    -5 ± 7.11
    -4.9 ± 6.16
    -6.6 ± 6.22
    Statistical analysis title
    Adalimumab 0.8 mg/kg versus MTX
    Comparison groups
    Methotrexate v Adalimumab 0.8 mg/kg
    Number of subjects included in analysis
    74
    Analysis specification
    Pre-specified
    Analysis type
    superiority [5]
    P-value
    = 0.304
    Method
    ANOVA
    Parameter type
    Difference
    Point estimate
    1.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.48
         upper limit
    4.7
    Notes
    [5] - Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

    Secondary: Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16

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    End point title
    Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16
    End point description
    The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best). LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    38
    38
    Units: units on a scale
        arithmetic mean (standard deviation)
    1.9 ± 10.41
    9.5 ± 12.25
    10.8 ± 15.38
    Statistical analysis title
    Adalimumab 0.8 mg/kg versus MTX
    Comparison groups
    Adalimumab 0.8 mg/kg v Methotrexate
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    superiority [6]
    P-value
    = 0.005
    Method
    ANOVA
    Parameter type
    Difference
    Point estimate
    -8.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.94
         upper limit
    -2.82
    Notes
    [6] - Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

    Secondary: Percentage of Subjects Achieving a PGA of "Cleared" or "Minimal" (0 or 1) Upon Re-Treatment in Period C

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    End point title
    Percentage of Subjects Achieving a PGA of "Cleared" or "Minimal" (0 or 1) Upon Re-Treatment in Period C
    End point description
    The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared; 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal; 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild; 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate; 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked; 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe. The percentage of participants achieving a score of clear (0) or minimal (1) is reported. Non-responder imputation was used, the analysis was conducted in the ITT population.
    End point type
    Secondary
    End point timeframe
    Period C, Week 16
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    8 [7]
    11 [8]
    19 [9]
    Units: percentage of subjects
        number (not applicable)
    62.5
    27.3
    52.6
    Notes
    [7] - Subjects in Period C
    [8] - Subjects in Period C
    [9] - Subjects in Period C
    Statistical analysis title
    Adalimumab 0.8mg/kg + MTX vs Adalimuimab 0.4 mg/kg
    Statistical analysis description
    The difference between the combined adalimumab 0.8 mg/kg + MTX groups and the adalimumab 0.4 mg/kg group.
    Comparison groups
    Adalimumab 0.8 mg/kg v Adalimumab 0.4 mg/kg v Methotrexate
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    superiority [10]
    P-value
    = 0.113
    Method
    Chi-squared
    Parameter type
    Difference
    Point estimate
    -28.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -60.6
         upper limit
    4
    Notes
    [10] - Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.

    Secondary: Time to Loss of Disease Control in Period B

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    End point title
    Time to Loss of Disease Control in Period B
    End point description
    Loss of disease control was defined as a worsening of PGA scores in comparison to Week 16 of Period A by at least 2 grades after treatment withdrawal. The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. Scores range from 0 (no evidence of scaling, erythema, or plaque elevation) to 5 (very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation). This analysis was conducted in the ITT population, no imputation was used.
    End point type
    Secondary
    End point timeframe
    Period B - 36 weeks
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    13 [11]
    18 [12]
    23 [13]
    Units: days
        median (inter-quartile range (Q1-Q3))
    184 (84 to 335)
    217 (56 to 551)
    118 (79 to 194)
    Notes
    [11] - Subjects in Period B
    [12] - Subjects in Period B
    [13] - Subjects in Period B
    Statistical analysis title
    Adalimumab 0.8 mg/kg versus MTX
    Statistical analysis description
    Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.
    Comparison groups
    Adalimumab 0.8 mg/kg v Methotrexate
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.343
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.66
         upper limit
    3.17
    Statistical analysis title
    Adalimumab 0.8 mg/kg versus Adalimumab 0.4 mg/kg
    Statistical analysis description
    Statistical comparisons for the ranked secondary endpoints were carried out in hierarchical order. All statistical tests were to be 2-sided with the significance level of 5%. Statistically significant results (P value ≤ 0.05) must have been achieved for a comparison in the higher rank in order to initiate the next comparison in the lower rank.
    Comparison groups
    Adalimumab 0.8 mg/kg v Adalimumab 0.4 mg/kg
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.276
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.71
         upper limit
    3.21

    Secondary: Percentage of Subjects Achieving a PGA of "Cleared" or "Minimal" (0 or 1) Over Time

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    End point title
    Percentage of Subjects Achieving a PGA of "Cleared" or "Minimal" (0 or 1) Over Time
    End point description
    The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared; 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal; 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild; 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate; 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked; 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe. The percentage of participants achieving a score of clear (0) or minimal (1) is reported. Non-responder imputation was used, the analysis was conducted in the ITT population.
    End point type
    Secondary
    End point timeframe
    Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
    number (not applicable)
        Period A, Week 4
    8.1
    20.5
    28.9
        Period A, Week 8
    8.1
    35.9
    44.7
        Period A, Week 11
    18.9
    30.8
    47.4
        Period C, Week 0 (n=8, 11, 19)
    0
    0
    0
        Period C, Week 16 (n=8, 11, 19)
    62.5
    27.3
    52.6
        Period D, Week 0 (n=36, 36, 36)
    30.6
    19.4
    38.9
        Period D, Week 16 (n=36, 36, 36)
    77.8
    38.9
    50
        Period D, Week 28 (n=36, 36, 36)
    69.4
    50
    63.9
        Period D, Week 40 (n=36, 36, 36)
    69.4
    50
    61.1
        Period D, Week 52 (n=36, 36, 36)
    75
    50
    55.6
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving a PGA of "Cleared" (0) Over Time

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    End point title
    Percentage of Subjects Achieving a PGA of "Cleared" (0) Over Time
    End point description
    The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared; 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal; 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild; 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate; 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked; 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe. The percentage of participants achieving a score of clear (0) is reported. Non-responder imputation was used, the analysis was conducted in the ITT population.
    End point type
    Secondary
    End point timeframe
    Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
    number (not applicable)
        Period A, Week 4
    0
    2.6
    2.6
        Period A, Week 8
    0
    12.8
    5.3
        Period A, Week 11
    0
    10.3
    10.5
        Period C, Week 0 (n=8, 11, 19)
    0
    0
    0
        Period C, Week 16 (n=8, 11, 19)
    25
    9.1
    15.8
        Period D, Week 0 (n=36, 36, 36)
    8.3
    5.6
    11.1
        Period D, Week 16 (n=36, 36, 36)
    25
    11.1
    25
        Period D, Week 28 (n=36, 36, 36)
    33.3
    16.7
    22.2
        Period D, Week 40 (n=36, 36, 36)
    33.3
    16.7
    27.8
        Period D, Week 52 (n=36, 36, 36)
    41.7
    25
    25
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved a PASI 50 Response Over Time

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    End point title
    Percentage of Subjects Who Achieved a PASI 50 Response Over Time
    End point description
    PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from Baseline in PASI score. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
    number (not applicable)
        Period A, Week 4
    16.2
    41
    52.6
        Period A, Week 8
    40.5
    56.4
    65.8
        Period A, Week 11
    51.4
    61.5
    71.1
        Period A, Week 16
    54.1
    66.7
    78.9
        Period C, Week 0 (n=8, 11, 19)
    62.5
    90.9
    52.6
        Period C, Week 16 (n=8, 11, 19)
    87.5
    90.9
    89.5
        Period D, Week 0 (n=36, 36, 36)
    52.8
    63.9
    75
        Period D, Week 16 (n=36, 36, 36)
    91.7
    69.4
    88.9
        Period D, Week 28 (n=36, 36, 36)
    88.9
    72.2
    86.1
        Period D, Week 40 (n=36, 36, 36)
    91.7
    63.9
    83.3
        Period D, Week 52 (n=36, 36, 36)
    91.7
    66.7
    77.8
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved a PASI 75 Response Over Time

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    End point title
    Percentage of Subjects Who Achieved a PASI 75 Response Over Time
    End point description
    PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from Baseline in PASI score. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
    number (not applicable)
        Period A, Week 4
    0
    15.4
    23.7
        Period A, Week 8
    13.5
    38.5
    47.4
        Period A, Week 11
    21.6
    43.6
    60.5
        Period C, Week 0 (n=8, 11, 19)
    37.5
    18.2
    21.1
        Period C, Week 16 (n=8, 11, 19)
    75
    54.5
    78.9
        Period D, Week 0 (n=36, 36, 36)
    30.6
    27.8
    50
        Period D, Week 16 (n=36, 36, 36)
    86.1
    50
    61.1
        Period D, Week 28 (n=36, 36, 36)
    80.6
    58.3
    77.8
        Period D, Week 40 (n=36, 36, 36)
    77.8
    52.8
    75
        Period D, Week 52 (n=36, 36, 36)
    86.1
    47.2
    72.2
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved a PASI 90 Response Over Time

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    End point title
    Percentage of Subjects Who Achieved a PASI 90 Response Over Time
    End point description
    PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from Baseline in PASI score. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
    number (not applicable)
        Period A, Week 4
    0
    5.1
    5.3
        Period A, Week 8
    2.7
    20.5
    23.7
        Period A, Week 11
    2.7
    28.2
    28.9
        Period C, Week 0 (n=8, 11, 19)
    0
    0
    10.5
        Period C, Week 16 (n=8, 11, 19)
    62.5
    27.3
    57.9
        Period D, Week 0 (n=36, 36, 36)
    25
    16.7
    36.1
        Period D, Week 16 (n=36, 36, 36)
    63.9
    36.1
    38.9
        Period D, Week 28 (n=36, 36, 36)
    55.6
    33.3
    41.7
        Period D, Week 40 (n=36, 36, 36)
    55.6
    36.1
    47.2
        Period D, Week 52 (n=36, 36, 36)
    66.7
    33.3
    44.4
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved a PASI 100 Response Over Time

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    End point title
    Percentage of Subjects Who Achieved a PASI 100 Response Over Time
    End point description
    PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-100 response is the percentage of participants who achieved a 100% reduction (improvement) from Baseline in PASI score. Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
    number (not applicable)
        Period A, Week 4
    0
    0
    2.6
        Period A, Week 8
    0
    5.1
    5.3
        Period A, Week 11
    0
    5.1
    10.5
        Period C, Week 0 (n=8, 11, 19)
    0
    0
    0
        Period C, Week 16 (n=8, 11, 19)
    25
    9.1
    15.8
        Period D, Week 0 (n=36, 36, 36)
    8.3
    5.6
    11.1
        Period D, Week 16 (n=36, 36, 36)
    13.9
    11.1
    25
        Period D, Week 28 (n=36, 36, 36)
    27.8
    13.9
    19.4
        Period D, Week 40 (n=36, 36, 36)
    30.6
    13.9
    22.2
        Period D, Week 52 (n=36, 36, 36)
    41.7
    25
    22.2
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in PASI Score Over Time

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    End point title
    Percent Change From Baseline in PASI Score Over Time
    End point description
    PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percent change
    arithmetic mean (standard deviation)
        Period A, Week 4
    -14 ± 36.71
    -36.9 ± 38.62
    -48.3 ± 33.96
        Period A, Week 8
    -30.6 ± 45.89
    -48.8 ± 44.74
    -60.3 ± 35.98
        Period A, Week 11
    -36.6 ± 51.69
    -51.4 ± 50.19
    -62.8 ± 38.02
        Period A, Week 16
    -42.8 ± 54.24
    -52.4 ± 51.79
    -65.6 ± 39.44
        Period C, Week 0 (n=8, 11, 19)
    -59 ± 20.61
    -65.3 ± 12.16
    -45.8 ± 39.64
        Period C, Week 16 (n=8, 11, 19)
    -87.1 ± 16.47
    -74.5 ± 17.79
    -69.3 ± 69.79
        Period D, Week 0 (n=36, 36, 36)
    -41.8 ± 54.99
    -46.8 ± 49.27
    -61.5 ± 42.96
        Period D, Week 16 (n=36, 36, 36)
    -82.3 ± 31.38
    -66.9 ± 33.51
    -74.5 ± 37.44
        Period D, Week 28 (n=36, 36, 36)
    -81 ± 35.86
    -65.8 ± 36.99
    -81.5 ± 22.06
        Period D, Week 40 (n=36, 36, 36)
    -83 ± 31.94
    -64.6 ± 37.46
    -82.1 ± 23.99
        Period D, Week 52 (n=36, 36, 36)
    -86.3 ± 28.92
    -58.7 ± 53.21
    -80.1 ± 24.17
    No statistical analyses for this end point

    Secondary: Change From Baseline in CDLQI Over Time

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    End point title
    Change From Baseline in CDLQI Over Time
    End point description
    The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Baseline, Period A, Weeks 4, and 8 , Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    36
    38
    38
    Units: units on a scale
    arithmetic mean (standard deviation)
        Period A, Week 4
    -2.9 ± 5.24
    -3.9 ± 5.22
    -4.9 ± 5.8
        Period A, Week 8
    -4 ± 6.44
    -4.1 ± 6.29
    -5.5 ± 5.66
        Period C, Week 0 (n=8, 11, 19)
    -6.1 ± 4.55
    -4.7 ± 9.08
    -6.1 ± 6.92
        Period C, Week 4 (n=8, 11, 19)
    -9.8 ± 3.92
    -5.5 ± 7.24
    -7 ± 6.63
        Period D, Week 0 (n=35, 35, 36)
    -5.6 ± 7.55
    -5.5 ± 5.95
    -6.8 ± 6.7
        Period D, Week 11 (n=35, 35, 36)
    -8.5 ± 5.37
    -6.8 ± 7.07
    -7.4 ± 6.21
        Period D, Week 28 (n=35, 35, 36)
    -8.3 ± 5.93
    -6.8 ± 7.91
    -8.4 ± 6.72
        Period D, Week 52 (n=35, 35, 36)
    -8.4 ± 6.08
    -6.6 ± 8.12
    -8.2 ± 6.75
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With CDLQI = 0 Over Time

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    End point title
    Percentage of Subjects With CDLQI = 0 Over Time
    End point description
    The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired and a score of 0 indicates no impairment in quality of life. Non-responder imputation was used, the analysis was conducted in the intent to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Period A, Weeks 4, 8 and 16 , Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: percentage of subjects
    number (not applicable)
        Period A, Week 4
    5.4
    5.1
    10.5
        Period A, Week 8
    10.8
    12.8
    5.3
        Period A, Week 16
    10.8
    20.5
    23.7
        Period C, Week 0 (n=8, 11, 19)
    0
    36.4
    21.1
        Period C, Week 4 (n=8, 11, 19)
    12.5
    36.4
    31.6
        Period D, Week 0 (n=36, 36, 36)
    16.7
    22.2
    27.8
        Period D, Week 11 (n=36, 36, 36)
    25
    16.7
    33.3
        Period D, Week 28 (n=36, 36, 36)
    30.6
    22.2
    30.6
        Period D, Week 52 (n=36, 36, 36)
    41.7
    16.7
    33.3
    No statistical analyses for this end point

    Secondary: Time to PASI 50/75/90/100 Response in Period A

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    End point title
    Time to PASI 50/75/90/100 Response in Period A
    End point description
    Subjects who did not have a response during Period A were censored. "99999" indicates parameters that were not estimable.
    End point type
    Secondary
    End point timeframe
    Period A, 16 weeks
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    39
    38
    Units: days
    median (inter-quartile range (Q1-Q3))
        PASI 50
    76 (56 to 112)
    55 (28 to 115)
    30 (28 to 77)
        PASI 75
    116 (111 to 99999)
    107 (56 to 99999)
    59 (53 to 99999)
        PASI 90
    99999 (112 to 99999)
    99999 (78 to 99999)
    99999 (76 to 99999)
        PASI 100
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Change From Baseline in PedsQL Over Time

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    End point title
    Change From Baseline in PedsQL Over Time
    End point description
    The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best). LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Baseline, Period A, Weeks 4 and 8 , Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    37
    38
    38
    Units: units on a scale
    arithmetic mean (standard deviation)
        Period A, Week 4 (n=37, 38, 36)
    -0.8 ± 11.75
    4.9 ± 13.8
    8.1 ± 11.95
        Period A, Week 8 (n=37, 38, 38)
    0.5 ± 10.18
    7 ± 13.16
    8.8 ± 15.45
        Period C, Week 0 (n=8, 11, 19)
    3 ± 10.45
    8.9 ± 25.35
    14.2 ± 20.25
        Period C, Week 4 (n=8, 11, 19)
    5.2 ± 11.08
    11.6 ± 25.19
    16.3 ± 17.35
        Period D, Week 0 (n=36, 36, 36)
    2.3 ± 10.93
    9.4 ± 16.9
    10.5 ± 15.86
        Period D, Week 11 (n=36, 36, 36)
    5.4 ± 10.36
    12.8 ± 19.03
    12 ± 16.13
        Period D, Week 28 (n=36, 36, 36)
    8 ± 13.4
    14.5 ± 20.19
    13.1 ± 16.23
        Period D, Week 52 (n=36, 36, 36)
    8.6 ± 13.93
    14 ± 20.4
    13.8 ± 15.36
    No statistical analyses for this end point

    Secondary: Change From Baseline in the Children's Depression Inventory: Short (CDI:S)

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    End point title
    Change From Baseline in the Children's Depression Inventory: Short (CDI:S)
    End point description
    The CDI:S is a short 10-item self-rated symptom-oriented scale used to screen for depressive symptoms. CDI:S scores range from 0 to 100, with a lower score indicating fewer depressive symptoms. LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.
    End point type
    Secondary
    End point timeframe
    Period A, Weeks 4, 8, and 16
    End point values
    Methotrexate Adalimumab 0.4 mg/kg Adalimumab 0.8 mg/kg
    Number of subjects analysed
    35
    35
    35
    Units: units on a scale
    arithmetic mean (standard deviation)
        Period A, Week 4 (n=35, 35, 34)
    0.6 ± 8.85
    -1 ± 6.64
    -3.6 ± 5.86
        Period A, Week 8 (n=35, 35, 34)
    0.2 ± 5.26
    -1.5 ± 7.52
    -1.6 ± 5.52
        Period A, Week 16 (n=35, 35, 35)
    -2 ± 5.88
    -3.3 ± 8.12
    -2.3 ± 6.29
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Period A - up to 16 weeks Period B - up to 36 weeks Period C - up to 16 weeks Period D - up to 52 weeks
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Period A: Methotrexate
    Reporting group description
    Subjects received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Subjects also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week dosing from Week 1.

    Reporting group title
    Period A: Adalimumab 0.4 mg/kg
    Reporting group description
    In Period A subjects received a single subcutaneous loading dose of adalimumab (ADA) 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets.

    Reporting group title
    Period A: Adalimumab 0.8 mg/kg
    Reporting group description
    In Period A subjects received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, subjects also received weekly dosing of methotrexate placebo tablets.

    Reporting group title
    Period B: MTX/No Treatment
    Reporting group description
    Subjects initially randomized to methotrexate who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.

    Reporting group title
    Period B: ADA 0.4 mg/kg/No Treatment
    Reporting group description
    Subjects initially randomized to adalimumab (ADA) 0.4 mg/kg who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.

    Reporting group title
    Period B: ADA 0.8 mg/kg/No Treatment
    Reporting group description
    Subjects initially randomized to adalimumab (ADA) 0.8 mg/kg who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.

    Reporting group title
    Period C: Adalimumab 0.4 mg/kg
    Reporting group description
    Subjects initially randomized to adalimumab 0.4 mg/kg with loss of disease control in Period B received adalimumab 0.4 mg/kg eow for up to 16 weeks in Period C.

    Reporting group title
    Period C: Adalimumab 0.8 mg/kg
    Reporting group description
    Subjects initially randomized to either methotrexate or adalimumab 0.8 mg/kg with loss of disease control in Period B received adalimumab 0.8 mg/kg eow for up to 16 weeks in Period C.

    Reporting group title
    Period D: Adalimumab 0.4 mg/kg
    Reporting group description
    Subjects received adalimumab 0.4 mg/kg eow for up to 52 weeks in Period D.

    Reporting group title
    Period D: Adalimumab 0.8 mg/kg
    Reporting group description
    Subjects received adalimumab 0.8 mg/kg eow for up to 52 weeks in Period D.

    Serious adverse events
    Period A: Methotrexate Period A: Adalimumab 0.4 mg/kg Period A: Adalimumab 0.8 mg/kg Period B: MTX/No Treatment Period B: ADA 0.4 mg/kg/No Treatment Period B: ADA 0.8 mg/kg/No Treatment Period C: Adalimumab 0.4 mg/kg Period C: Adalimumab 0.8 mg/kg Period D: Adalimumab 0.4 mg/kg Period D: Adalimumab 0.8 mg/kg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 37 (0.00%)
    3 / 39 (7.69%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    1 / 23 (4.35%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    5 / 87 (5.75%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Hand Fracture
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 39 (2.56%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon Injury
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Eye Naevus
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest Pain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 39 (2.56%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Haemorrhagic Ovarian Cyst
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    1 / 23 (4.35%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash Maculo-Papular
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gastrointestinal Infection
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 39 (2.56%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Period A: Methotrexate Period A: Adalimumab 0.4 mg/kg Period A: Adalimumab 0.8 mg/kg Period B: MTX/No Treatment Period B: ADA 0.4 mg/kg/No Treatment Period B: ADA 0.8 mg/kg/No Treatment Period C: Adalimumab 0.4 mg/kg Period C: Adalimumab 0.8 mg/kg Period D: Adalimumab 0.4 mg/kg Period D: Adalimumab 0.8 mg/kg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    23 / 37 (62.16%)
    27 / 39 (69.23%)
    23 / 38 (60.53%)
    6 / 13 (46.15%)
    6 / 18 (33.33%)
    6 / 23 (26.09%)
    5 / 11 (45.45%)
    16 / 27 (59.26%)
    8 / 13 (61.54%)
    64 / 87 (73.56%)
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    3 / 87 (3.45%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    3
    Joint Injury
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    1 / 13 (7.69%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Laceration
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    1 / 13 (7.69%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Thermal Burn
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    1 / 13 (7.69%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin Papilloma
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 39 (2.56%)
    0 / 38 (0.00%)
    1 / 13 (7.69%)
    0 / 18 (0.00%)
    1 / 23 (4.35%)
    0 / 11 (0.00%)
    2 / 27 (7.41%)
    0 / 13 (0.00%)
    4 / 87 (4.60%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    0
    2
    0
    7
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    1 / 13 (7.69%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Cough
         subjects affected / exposed
    1 / 37 (2.70%)
    4 / 39 (10.26%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    2 / 18 (11.11%)
    0 / 23 (0.00%)
    2 / 11 (18.18%)
    1 / 27 (3.70%)
    1 / 13 (7.69%)
    4 / 87 (4.60%)
         occurrences all number
    1
    4
    1
    0
    2
    0
    2
    1
    1
    4
    Dyspnoea
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    1 / 13 (7.69%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Epistaxis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    1 / 13 (7.69%)
    3 / 87 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    4
    Oropharyngeal Pain
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 39 (2.56%)
    2 / 38 (5.26%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    1 / 27 (3.70%)
    0 / 13 (0.00%)
    6 / 87 (6.90%)
         occurrences all number
    2
    1
    2
    0
    0
    0
    0
    1
    0
    7
    Rhinorrhoea
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 39 (2.56%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    1 / 13 (7.69%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    0
    0
    1
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    4 / 37 (10.81%)
    7 / 39 (17.95%)
    6 / 38 (15.79%)
    1 / 13 (7.69%)
    2 / 18 (11.11%)
    1 / 23 (4.35%)
    0 / 11 (0.00%)
    3 / 27 (11.11%)
    1 / 13 (7.69%)
    22 / 87 (25.29%)
         occurrences all number
    8
    11
    7
    1
    2
    3
    0
    3
    1
    30
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 37 (2.70%)
    2 / 39 (5.13%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Chest Pain
         subjects affected / exposed
    2 / 37 (5.41%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Fatigue
         subjects affected / exposed
    2 / 37 (5.41%)
    4 / 39 (10.26%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    2 / 27 (7.41%)
    0 / 13 (0.00%)
    4 / 87 (4.60%)
         occurrences all number
    2
    4
    0
    0
    0
    0
    0
    3
    0
    4
    Injection Site Pain
         subjects affected / exposed
    3 / 37 (8.11%)
    1 / 39 (2.56%)
    3 / 38 (7.89%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    1 / 27 (3.70%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    3
    1
    3
    0
    0
    0
    0
    1
    0
    1
    Injection Site Reaction
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 39 (2.56%)
    2 / 38 (5.26%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    1 / 27 (3.70%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    0
    1
    0
    3
    Pyrexia
         subjects affected / exposed
    1 / 37 (2.70%)
    3 / 39 (7.69%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    1 / 13 (7.69%)
    4 / 87 (4.60%)
         occurrences all number
    1
    3
    1
    0
    1
    0
    0
    0
    1
    5
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    1 / 13 (7.69%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    1 / 11 (9.09%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    4 / 37 (10.81%)
    1 / 39 (2.56%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    4 / 87 (4.60%)
         occurrences all number
    4
    1
    1
    0
    0
    0
    0
    0
    0
    4
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 39 (5.13%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    1 / 23 (4.35%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    6 / 87 (6.90%)
         occurrences all number
    0
    5
    1
    0
    0
    1
    0
    0
    0
    7
    Diarrhoea
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 39 (2.56%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    1 / 27 (3.70%)
    0 / 13 (0.00%)
    6 / 87 (6.90%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    6
    Dyspepsia
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 39 (5.13%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    4 / 37 (10.81%)
    3 / 39 (7.69%)
    2 / 38 (5.26%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    2 / 27 (7.41%)
    1 / 13 (7.69%)
    10 / 87 (11.49%)
         occurrences all number
    5
    3
    2
    0
    0
    0
    0
    2
    1
    11
    Vomiting
         subjects affected / exposed
    0 / 37 (0.00%)
    3 / 39 (7.69%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    2 / 27 (7.41%)
    0 / 13 (0.00%)
    3 / 87 (3.45%)
         occurrences all number
    0
    3
    1
    0
    1
    0
    0
    2
    0
    5
    Skin and subcutaneous tissue disorders
    Dry Skin
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 39 (0.00%)
    3 / 38 (7.89%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    1 / 27 (3.70%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences all number
    1
    0
    3
    0
    0
    0
    0
    1
    0
    0
    Eczema
         subjects affected / exposed
    0 / 37 (0.00%)
    2 / 39 (5.13%)
    1 / 38 (2.63%)
    1 / 13 (7.69%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    4 / 87 (4.60%)
         occurrences all number
    0
    2
    1
    1
    0
    0
    0
    0
    0
    7
    Eczema Vesicular
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    1 / 13 (7.69%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 37 (2.70%)
    3 / 39 (7.69%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    1 / 11 (9.09%)
    1 / 27 (3.70%)
    0 / 13 (0.00%)
    4 / 87 (4.60%)
         occurrences all number
    1
    3
    1
    0
    0
    0
    2
    1
    0
    4
    Pruritus Generalised
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    1 / 11 (9.09%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Psoriasis
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 39 (2.56%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    1 / 23 (4.35%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    1 / 13 (7.69%)
    6 / 87 (6.90%)
         occurrences all number
    1
    1
    1
    0
    0
    1
    0
    0
    1
    6
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 37 (5.41%)
    1 / 39 (2.56%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    1 / 23 (4.35%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    3 / 87 (3.45%)
         occurrences all number
    2
    1
    1
    0
    0
    1
    0
    0
    0
    4
    Back Pain
         subjects affected / exposed
    0 / 37 (0.00%)
    1 / 39 (2.56%)
    2 / 38 (5.26%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    3 / 27 (11.11%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    2
    2
    0
    0
    0
    0
    3
    0
    2
    Joint Effusion
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    1 / 13 (7.69%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Musculoskeletal Pain
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 39 (2.56%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    1 / 11 (9.09%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    1
    0
    0
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    1 / 23 (4.35%)
    0 / 11 (0.00%)
    1 / 27 (3.70%)
    0 / 13 (0.00%)
    5 / 87 (5.75%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    6
    Gastroenteritis
         subjects affected / exposed
    3 / 37 (8.11%)
    0 / 39 (0.00%)
    2 / 38 (5.26%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    1 / 11 (9.09%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    3
    0
    2
    0
    0
    0
    1
    0
    0
    1
    Influenza
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    9 / 87 (10.34%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    10
    Lice Infestation
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    1 / 13 (7.69%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    7 / 37 (18.92%)
    10 / 39 (25.64%)
    8 / 38 (21.05%)
    0 / 13 (0.00%)
    1 / 18 (5.56%)
    4 / 23 (17.39%)
    1 / 11 (9.09%)
    5 / 27 (18.52%)
    3 / 13 (23.08%)
    25 / 87 (28.74%)
         occurrences all number
    9
    11
    10
    0
    1
    4
    1
    5
    3
    36
    Oral Herpes
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 39 (0.00%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    2 / 27 (7.41%)
    0 / 13 (0.00%)
    2 / 87 (2.30%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    2
    0
    2
    Pharyngitis
         subjects affected / exposed
    1 / 37 (2.70%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    1 / 27 (3.70%)
    0 / 13 (0.00%)
    6 / 87 (6.90%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    8
    Pharyngitis Streptococcal
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    1 / 38 (2.63%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    1 / 13 (7.69%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Rhinitis
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 39 (2.56%)
    3 / 38 (7.89%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    0 / 13 (0.00%)
    3 / 87 (3.45%)
         occurrences all number
    1
    1
    3
    0
    0
    0
    0
    0
    0
    3
    Upper Respiratory Tract Infection
         subjects affected / exposed
    6 / 37 (16.22%)
    4 / 39 (10.26%)
    2 / 38 (5.26%)
    0 / 13 (0.00%)
    2 / 18 (11.11%)
    1 / 23 (4.35%)
    0 / 11 (0.00%)
    3 / 27 (11.11%)
    0 / 13 (0.00%)
    13 / 87 (14.94%)
         occurrences all number
    8
    4
    2
    0
    3
    1
    0
    3
    0
    17
    Urinary Tract Infection
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    1 / 13 (7.69%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    1 / 27 (3.70%)
    0 / 13 (0.00%)
    1 / 87 (1.15%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    1
    Varicella
         subjects affected / exposed
    0 / 37 (0.00%)
    0 / 39 (0.00%)
    0 / 38 (0.00%)
    0 / 13 (0.00%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    0 / 27 (0.00%)
    1 / 13 (7.69%)
    0 / 87 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Viral Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 37 (2.70%)
    1 / 39 (2.56%)
    1 / 38 (2.63%)
    1 / 13 (7.69%)
    0 / 18 (0.00%)
    0 / 23 (0.00%)
    0 / 11 (0.00%)
    2 / 27 (7.41%)
    0 / 13 (0.00%)
    2 / 87 (2.30%)
         occurrences all number
    1
    1
    1
    1
    0
    0
    0
    3
    0
    3

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Oct 2008
    ● added explanation for even-week dosing for Period D. ● updated adalimumab worldwide approval status for Rheumatoid Arthritis. ● updated Overall Study Design and Plan: minimum screening period changed from 48 to 72 hours, added information for the non-investigational medicinal product folic acid, added that subjects must complete all 16 weeks of treatment in Period C in order to be eligible to enter Period D. ● Study activities updated to remove the Family Dermatology Quality of Life Index (FDLQI), added the Children's Depression Index:Short (CDI:S) at Week 4A and 8A visits and removed all patient reported outcomes (PROs) from Week 11A visit, general labs and urinalysis were added at Weeks 0D and 52D; pharmacokinetic (PK)/Anti-adalimumab antibody (AAA) sample collection was added at Week 8D. ● Study procedures updated: language added regarding tuberculosis screening, lab analyses, FDLQI removed, CDLQI cartoon version removed, PedsQL parent proxy report for children ages 5-7 removed, information added for folic acid. ● Drug Concentration Measurements: removed sample collection at Week 16C and added sample collection at Week 8D. ● Secondary Variable, Ranked – Removed FDLQI ● Treatments Administered: Information for MTX was added, adalimumab dosing schedules for Periods A, C, and D were added and Information for folic acid was added.
    15 Mar 2011
    ● Update the date related to the number of countries that adalimumab has been approved ● Add information on the maximum time subject would be participating in the study ● Added Differences Statement. ● Update inclusion criterion number 10 to include the QuantiFERON-TB Gold or equivalent test. ● Add new inclusion criterion number 16 regarding updated immunization schedule. ● Add wording on clinically significant abnormal screening laboratory results to exclusion criterion number 20. ● Provide new information on Hepatitis B testing for exclusion criterion number 14. ● Add new exclusion criterion number 23 regarding viral infections, and to incorporate adalimumab 0.8 mg/kg protocol wording. ● Add new exclusion criterion number 24 related to GFR. ● Add new exclusion criterion number 25 related to Hepatitis C. ● Add additional prohibited medications. ● Add general labs (hematology and chemistry) to the Week 8A visit Study Activities (Period A). ● Add additional time point for assessment of hs-CRP to Study Activities (Period D). ● Update chest x-ray and TB screening sections to include new information on QuantiFERON-TB Gold or equivalent test and to add content to include new adalimumab protocol standard wording. Add clarification that subjects enrolled under TB prophylaxis must continue the prophylaxis until entire course was completed. ● Add instruction for measurement of waist circumference at level of umbilicus for metabolic syndrome screening and reference to WHO Child Growth Charts. ● Add instructions on which version of PedsQL to complete as child ages during study. ● Add guidance on scheduling annual TB testing.
    18 Jul 2013
    ● Updated Adalimumab Overview to reflect current information, as provided in the updated Investigator's Brochure version 19. ● Added Safety Information: section added to include new safety monitoring information. ● Updated Prior and Concomitant Therapy: added collection requirements for events of malignancy in patients 30 years of age or younger. ● Updated Prohibited Medications with newly available biologic therapies that are prohibited while in the study. ● Updated the following sections to comply with the Humira® standard protocol language in compliance with Investigator's Brochure version 19 (dated May 2013) and AbbVie policies and procedures: - Discontinuation of Individual Subjects: added that noncompliance with TB prophylaxis was grounds for discontinuation; removed the language regarding inclusion/exclusion criteria where safety was involved, as violations of inclusion and/or exclusion criteria are not necessarily grounds for discontinuation and are handled by the study designated physician; for protocol consistency changed medical monitor to study designated physician. - Drug Accountability: differentiated between the refrigerated and nonrefrigerated study drug; clarification made to differentiated drug dispensing depot from drug destruction depot. - Protocol Deviations: statement added that AbbVie does not grant waivers or allow any known or prospective protocol deviations. ● Adverse Event Reporting: added new requirements for reporting any serious adverse event or nonserious event of malignancy in patients 30 years of age or younger.

    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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