Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   36059   clinical trials with a EudraCT protocol, of which   5925   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A 12-week randomized, double-blind, placebo-controlled, parallel-group, 2-arm study to evaluate the efficacy and safety of tocilizumab in patients with active systemic juvenile idiopathic arthritis (sJIA); with a 92-week single arm open-label extension to examine the long term use of tocilizumab, followed by a 3 year open-label continuation of the study to examine the long term use of tocilizumab

    Summary
    EudraCT number
    2007-000872-18
    Trial protocol
    BE   SE   DE   NO   CZ   ES   DK   NL   GR   SK   IT   GB  
    Global end of trial date
    05 Aug 2014

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

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    WA18221
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00642460
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, CH-4070, Basel, Switzerland,
    Public contact
    F. Hoffmann-La Roche AG, Roche Trial Information Hotline, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, Roche Trial Information Hotline, +41 616878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000309-PIP02-14
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    04 Oct 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Aug 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Part I: Primary Objectives: 1. To assess the efficacy of tocilizumab versus placebo in combination with stable ongoing therapy at 12 weeks, with regard to signs and symptoms in sJIA patients with persistent activity and an inadequate response to Non-Steroid Anti-Inflammatory Drugs (NSAIDs) and systemic corticosteroids. Part II: Primary Objectives: 1. To evaluate the safety of tocilizumab in chronic administration and to assess the effect of tocilizumab to enable the reduction or elimination of corticosteroids. Part III: Primary Objective: To assess the long-term safety of 8 mg/kg tocilizumab in children greater than or equal to (≥) 30 kg and 12 mg/kg TCZ in children less than (<) 30 kg with regard to adverse events and laboratory result abnormalities.
    Protection of trial subjects
    The study was conducted in accordance with the principals or laws of the country in which the study was conducted to ensure maximum protection to the individual. The study fully adhered to the provisions in "Principles of Good Clinical Practice" in the respective countries.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    09 May 2008
    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
    Argentina: 12
    Country: Number of subjects enrolled
    Australia: 5
    Country: Number of subjects enrolled
    Brazil: 6
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    Mexico: 4
    Country: Number of subjects enrolled
    United States: 18
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Norway: 2
    Country: Number of subjects enrolled
    Poland: 3
    Country: Number of subjects enrolled
    Slovakia: 1
    Country: Number of subjects enrolled
    Spain: 10
    Country: Number of subjects enrolled
    United Kingdom: 8
    Country: Number of subjects enrolled
    Belgium: 8
    Country: Number of subjects enrolled
    Czech Republic: 3
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    Italy: 13
    Worldwide total number of subjects
    112
    EEA total number of subjects
    61
    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)
    70
    Adolescents (12-17 years)
    42
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    This study consists of 3 parts. Part I: a 12 week double-blind placebo controlled study followed by Part II: a 92 week single arm open-label extension study followed by Part III: a 3 year open label continuation study.

    Period 1
    Period 1 title
    Part I: 12 Week Double-Blind
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind [1]
    Roles blinded
    Subject, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Tocilizumab_8 mg/kg
    Arm description
    Tocilizumab 8 milligrams per kilogram (mg/kg) (for patients greater than or equal to [≥] 30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part I Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
    Arm type
    Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients weighing≥30 kg received 8 mg/kg iv every 2 weeks for 12 weeks in Part I.

    Arm title
    Tocilizumab_12 mg/kg
    Arm description
    Tocilizumab 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part I and every 2 weeks for 92 weeks in Part II. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable
    Arm type
    Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients weighing less than (<) 30 kg received 12 mg/kg iv every 2 weeks for 12 weeks in Part I.

    Arm title
    Placebo
    Arm description
    Placebo iv every 2 weeks for 12 weeks in Part 1. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients received placebo infusion iv every 2 weeks for 12 weeks.

    Notes
    [1] - The roles blinded appear to be inconsistent with a double blind trial.
    Justification: Investigator was not blinded in this study.
    Number of subjects in period 1
    Tocilizumab_8 mg/kg Tocilizumab_12 mg/kg Placebo
    Started
    37
    38
    37
    Completed
    36
    37
    36
    Not completed
    1
    1
    1
         Refused Treatment
    1
    -
    -
         Adverse event, non-fatal
    -
    1
    1
    Period 2
    Period 2 title
    Part II: Open-Label Up to Week 92
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Tocilizumab_8 mg/kg
    Arm description
    Tocilizumab 8 mg/kg (for patients ≥30 kg) iv every 2 weeks for 92 weeks. Participants remained on their prescribed standard of care treatment with (NSAIDs, methotrexate and corticosteroids if applicable.
    Arm type
    Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients weighing≥30 kg received 8 mg/kg iv every 2 weeks for 12 weeks in Part I and every 2 weeks for 92 weeks in Part II.

    Arm title
    Tocilizumab_12 mg/kg
    Arm description
    Tocilizumab 12 mg/kg (for patients <30 kg) iv every 2 weeks for 92 weeks. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
    Arm type
    Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients weighing < 30 kg received 12 mg/kg iv every 2 weeks for 12 weeks in Part I and every 2 weeks for 92 weeks in Part II.

    Arm title
    Tocilizumab Switchers
    Arm description
    Tocilizumab Switchers includes all participants who changed their dose either Tocilizumab 8 mg/kg or 12 mg/kg iv every 2 weeks in Part II. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
    Arm type
    Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients weighing ≥30 kg received 8 mg/kg and those weighing < 30 kg received 12 mg/kg iv every 2 weeks for 92 weeks.

    Number of subjects in period 2
    Tocilizumab_8 mg/kg Tocilizumab_12 mg/kg Tocilizumab Switchers
    Started
    52
    40
    20
    Completed
    43
    32
    17
    Not completed
    9
    8
    3
         Refused Treatment
    3
    1
    -
         Adverse event, serious fatal
    -
    1
    2
         Insufficient therapeutic response
    2
    3
    -
         Adverse event, non-fatal
    4
    2
    -
         Administrative reasons
    -
    -
    1
         Lost to follow-up
    -
    1
    -
    Period 3
    Period 3 title
    Part III Open Label Period
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Participants ≥30 kg
    Arm description
    Tocilizumab 8 mg/kg iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks up to 260 weeks in Part III based on the body weight (BW) recorded at Baseline. The dose of TCZ could be adjusted for non-transient changes in BW (< 30 kg to ≥ 30 kg) over a minimum of 3 consecutive visits.
    Arm type
    Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    8 mg/kg (for patients ≥30 kg) iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks up to 260 weeks in Part III.

    Arm title
    Participants <30 kg
    Arm description
    Tocilizumab 12 mg/kg iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks up to 260 weeks in Part III based on the BW recorded at Baseline. The dose of TCZ could be adjusted for non-transient changes in BW ( 30 kg to ≥ 30 kg) over a minimum of 3 consecutive visits.
    Arm type
    Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    12 mg/kg iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks up to 260 weeks in Part III.

    Arm title
    All Tocilizumab
    Arm description
    Tocilizumab either 8 mg/kg (participants ≥ 30 kg) or 12 mg/kg (participants <30 kg) iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
    Arm type
    Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    8 mg/kg (for patients ≥30 kg) or 12 mg/kg (participants <30 kg) iv every 2 weeks for 12 weeks in Part I and every 2 weeks for 92 weeks in Part II and every 2 weeks for 156 weeks in Part III.

    Number of subjects in period 3
    Participants ≥30 kg Participants <30 kg All Tocilizumab
    Started
    53
    59
    112
    Completed on Q2W
    28
    38
    66 [2]
    Went into Alternative Dosing
    23 [3]
    22 [4]
    39 [5]
    Withdrawn from Alternative Dosing
    6 [6]
    2 [7]
    7 [8]
    Withdrawn from Q2W
    19 [9]
    19 [10]
    39 [11]
    Completed Alternative Dosing
    12 [12]
    20 [13]
    32 [14]
    Completed
    28
    38
    73
    Not completed
    25
    21
    39
         Adverse event
    7
    -
    -
         Refused Treatment
    8
    3
    11
         Adverse event, serious fatal
    -
    3
    3
         Unknown reasons
    2
    2
    -
         Adverse event, non-fatal
    -
    6
    12
         Insufficient therapeutic response
    3
    4
    7
         Unspecified
    -
    -
    4
         Consent withdrawn by subject
    4
    1
    -
         Administrative reasons
    -
    1
    -
         Lost to follow-up
    1
    1
    2
    Notes
    [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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [7] - 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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [8] - 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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [9] - 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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [10] - 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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [11] - 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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [12] - 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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [13] - 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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.
    [14] - 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: Participants were allowed to participate in an alternative dosing schedule if a participant had an inactive disease status and was not receiving oral CS for the previous 12 consecutive weeks and met certain protocol-defined criteria. Not all participants entered the alternative dosing schedule.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Part I: 12 Week Double-Blind
    Reporting group description
    Patients received either Tocilizumab 8 mg/kg (for patients ≥30 kg) or 12 mg/kg (for patients <30 kg) iv every 2 weeks for 12 weeks or placebo iv every 2 weeks for 12 weeks in Part I of the study. All patients remained on their prescribed standard of care treatment with non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate and corticosteroids if applicable.

    Reporting group values
    Part I: 12 Week Double-Blind Total
    Number of subjects
    112 112
    Age categorical
    Units: Subjects
        2 to 5
    27 27
        6 to 12
    48 48
        13 to 17
    37 37
    Gender categorical
    Units: Subjects
        Female
    56 56
        Male
    56 56

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Tocilizumab_8 mg/kg
    Reporting group description
    Tocilizumab 8 milligrams per kilogram (mg/kg) (for patients greater than or equal to [≥] 30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part I Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.

    Reporting group title
    Tocilizumab_12 mg/kg
    Reporting group description
    Tocilizumab 12 mg/kg (for patients <30 kg) intravenous (iv) every 2 weeks for 12 weeks in Part I and every 2 weeks for 92 weeks in Part II. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable

    Reporting group title
    Placebo
    Reporting group description
    Placebo iv every 2 weeks for 12 weeks in Part 1. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
    Reporting group title
    Tocilizumab_8 mg/kg
    Reporting group description
    Tocilizumab 8 mg/kg (for patients ≥30 kg) iv every 2 weeks for 92 weeks. Participants remained on their prescribed standard of care treatment with (NSAIDs, methotrexate and corticosteroids if applicable.

    Reporting group title
    Tocilizumab_12 mg/kg
    Reporting group description
    Tocilizumab 12 mg/kg (for patients <30 kg) iv every 2 weeks for 92 weeks. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.

    Reporting group title
    Tocilizumab Switchers
    Reporting group description
    Tocilizumab Switchers includes all participants who changed their dose either Tocilizumab 8 mg/kg or 12 mg/kg iv every 2 weeks in Part II. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.
    Reporting group title
    Participants ≥30 kg
    Reporting group description
    Tocilizumab 8 mg/kg iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks up to 260 weeks in Part III based on the body weight (BW) recorded at Baseline. The dose of TCZ could be adjusted for non-transient changes in BW (< 30 kg to ≥ 30 kg) over a minimum of 3 consecutive visits.

    Reporting group title
    Participants <30 kg
    Reporting group description
    Tocilizumab 12 mg/kg iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks up to 260 weeks in Part III based on the BW recorded at Baseline. The dose of TCZ could be adjusted for non-transient changes in BW ( 30 kg to ≥ 30 kg) over a minimum of 3 consecutive visits.

    Reporting group title
    All Tocilizumab
    Reporting group description
    Tocilizumab either 8 mg/kg (participants ≥ 30 kg) or 12 mg/kg (participants <30 kg) iv every 2 weeks for 12 weeks in Part I, every 2 weeks for 92 weeks in Part II and every 2 weeks for 156 weeks in Part III. Participants remained on their prescribed standard of care treatment with NSAIDs, methotrexate and corticosteroids if applicable.

    Primary: Part I: Percentage of Participants With ≥30 percent (%) Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever

    Close Top of page
    End point title
    Part I: Percentage of Participants With ≥30 percent (%) Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever [1] [2]
    End point description
    Percentage of participants with ≥30% improvement in ACR core set consisting of 6 components: 1) Physician's global assessment of disease activity Visual Analog Scale (VAS), 2) Parent/Patient global assessment of overall well-being VAS, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) consisting of 30 questions in 8 domains. Absence of fever was defined as no diary temperature recording ≥37.5 degrees Celsius in the preceding seven days. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    Baseline, Week 12
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    37
    75
    Units: percentage of participants
        number (not applicable)
    24.3
    85.3
    No statistical analyses for this end point

    Primary: Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104

    Close Top of page
    End point title
    Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104 [3]
    End point description
    Percentage of participants with ≥20 percent, ≥50 percent, ≥75 percent and ≥90 percent decreases in oral corticosteroid dose (mg/kg/day) from baseline. Analysis included only participants on oral corticosteroids at baseline.
    End point type
    Primary
    End point timeframe
    Baseline, Week 104
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    All Tocilizumab
    Number of subjects analysed
    55
    Units: percentage of participants
    number (not applicable)
        ≥20 percent decrease
    76
        ≥50 percent decrease
    73
        ≥75 percent decrease
    62
        ≥90 percent decrease
    47
    No statistical analyses for this end point

    Secondary: Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12

    Close Top of page
    End point title
    Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12 [4]
    End point description
    The six JIA ACR components consist of: 1)Physician's global assessment of disease activity, 2)Parent/Patient global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) CHAQ-DI. At an assessment visit a JIA ACR30/50/70/90 response in comparison to Baseline is defined as: At least three of the six JIA ACR core components improving by at least 30%/50%/70%/90% and no more than one of the remaining JIA ACR core components worsening by more than 30%. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    37
    75
    Units: percentage of participants
    number (not applicable)
        JIA ACR30 response
    24.3
    90.7
        JIA ACR50 response
    10.8
    85.3
        JIA ACR70 response
    8.1
    70.7
        JIA ACR90 response
    5.4
    37.3
    No statistical analyses for this end point

    Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity

    Close Top of page
    End point title
    Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity [5]
    End point description
    Physician's Global Assessment of disease activity is a Visual Analog Scale. The scale is 0 to 100 mm horizontal scale, the extreme left end of the line represents ‘arthritis inactive’ (i.e. symptom-free and no arthritis symptoms) and the extreme right end represents ‘arthritis very active’. This item is completed by the treating physician. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined were excluded. LOCF rule applied to missing JIA ACR core set components at Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    17
    73
    Units: percentage change
        number (not applicable)
    -41.1
    -69.6
    No statistical analyses for this end point

    Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being

    Close Top of page
    End point title
    Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being [6]
    End point description
    The Parent/Patient global assessment of overall well-being is a VAS. The scale is a 0 to 100 mm horizontal scale, the extreme left end of the line represents ‘very well’ (i.e. symptom-free and no arthritis disease activity) and the extreme right end represents ‘very poor’ (i.e. maximum arthritis disease activity). This item is completed by the patient or parent/guardian as appropriate.Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are excluded. LOCF rule applied to missing JIA ACR core set components at Week 12. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    17
    73
    Units: percentage change
        number (not applicable)
    -1.4
    -65.8
    No statistical analyses for this end point

    Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis

    Close Top of page
    End point title
    Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis [7]
    End point description
    The maximum number of joints with active arthritis is 71 and these are defined as those in the joint assessment with: swelling present or pain present and limitation of motion. The joint assessment is performed by an independent assessor, who is not the treating physician, blinded to all other aspects of the patient’s efficacy and safety data.Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are excluded. LOCF rule applied to missing JIA ACR core set components at Week 12. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    17
    73
    Units: percentage change
        number (not applicable)
    -37.2
    -70.6
    No statistical analyses for this end point

    Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement

    Close Top of page
    End point title
    Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement [8]
    End point description
    The maximum number of joints with limitation of movement is 67 and these are defined as those in the joint assessment with ‘limitation of motion’. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug. Patients who withdrew, received escape medication, or for whom the endpoint could not be determined were excluded. LOCF rule applied to missing JIA ACR core set components at Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    17
    72
    Units: percentage change
        number (not applicable)
    -22.5
    -51.6
    No statistical analyses for this end point

    Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate

    Close Top of page
    End point title
    Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Erythrocyte Sedimentation Rate [9]
    End point description
    Erythrocyte Sedimentation Rate (ESR) is an acute phase reactant measured in mm/hour. Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug. Patients who withdrew, received escape medication, or for whom the endpoint could not be determined were excluded. LOCF rule applied to missing JIA ACR core set components at Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    17
    73
    Units: percentage change
        number (not applicable)
    33.6
    -88.2
    No statistical analyses for this end point

    Secondary: Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI)

    Close Top of page
    End point title
    Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI) [10]
    End point description
    Functional ability is assessed using the CHAQ-DI. The questionnaire consists of 30 questions referring to eight domains; dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain has at least two component questions and if applicable to the patient there are four possible responses (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do). The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug. Patients who withdrew, received escape medication, or for whom the endpoint could not be determined were excluded. LOCF rule applied to missing JIA ACR core set components at Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    17
    72
    Units: percentage change
        number (not applicable)
    -10.3
    -45.6
    No statistical analyses for this end point

    Secondary: Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12

    Close Top of page
    End point title
    Part I: Percentage of Participants With Fever Due to Systemic Juvenile Idiopathic Arthritis (sJIA) at Baseline Who Are Free of Fever at Week 12 [11]
    End point description
    Fever free was defined as no diary temperature recording ≥37.5° Celsius in the preceding fourteen days. Participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) who had a fever due to Systemic Juvenile Idiopathic Arthritis at baseline were included in analysis.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    24
    41
    Units: percentage of participants
        number (not applicable)
    20.8
    85.4
    No statistical analyses for this end point

    Secondary: Part I: Percentage of Participants With Changes in Laboratory Indicators: High-sensitivity C-Reactive Protein (hsCRP), Hemoglobin (Hb), Platelets and Leukocytes From Abnormal at Baseline to Normal at Week 12

    Close Top of page
    End point title
    Part I: Percentage of Participants With Changes in Laboratory Indicators: High-sensitivity C-Reactive Protein (hsCRP), Hemoglobin (Hb), Platelets and Leukocytes From Abnormal at Baseline to Normal at Week 12 [12]
    End point description
    Percentage of participants with a change from an elevated hsCRP value at baseline to a normal hsCRP value at week 12; a change from anemia (low Hemoglobin) at baseline to a normal hemoglobin value at week 12; a change from thrombocytosis (elevated platelets) at baseline to a normal platelet value at week 12; a change from leukocytosis (elevated white blood cell count) at baseline to a normal white blood cell count at week 12.Analysis was performed on Intent-to-treat population which included all participants who had at least one dose of study drug. 'n' in each of the categories is the number of participants with data available at baseline and week 12 for analyses.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    37
    75
    Units: percentage of participants
    number (not applicable)
        hsC-Reactive Protein (n=34,72)
    5.9
    98.6
        Hemoglobin (n=29,50)
    6.9
    80
        Platelets (n=26,52)
    3.8
    90.4
        Leukocytes (n=21,28)
    9.5
    75
    No statistical analyses for this end point

    Secondary: Part I: Percentage of Participants With Concomitant Corticosteroid Reduction

    Close Top of page
    End point title
    Part I: Percentage of Participants With Concomitant Corticosteroid Reduction [13]
    End point description
    The percentage of participants receiving oral corticosteroids(CS) with a JIA ACR70 response at week 6 or Week 8 who reduced their oral CS dose by at least 20% without subsequent JIA ACR30 flare or occurrence of systemic symptoms at week 12. At an assessment visit a JIA ACR70 response is defined as: At least three of the six JIA ACR core components improving by at least 70% and no more than one of the remaining JIA ACR core components worsening by more than 30%. Analysis was performed on participants from the Intent-to-treat population (all randomized participants who received at least one dose of study drug) who were taking oral corticosteroids.
    End point type
    Secondary
    End point timeframe
    Week 6 or Week 8, Week 12
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    31
    70
    Units: percentage of participants
        number (not applicable)
    3.2
    24.3
    No statistical analyses for this end point

    Secondary: Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12

    Close Top of page
    End point title
    Part I: Change From Baseline in the Pain Visual Analog Scale (VAS) at Week 12 [14]
    End point description
    Participants rated their pain by placing a horizontal line on a Visual Analog Scale on a scale of 0 (no pain)- 100 mm (severe pain). The score at 12 weeks minus the score at baseline. A negative number indicates improvement. Participants from the Intent-to-treat population who had Pain VAS data available at baseline and week 12. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are excluded. LOCF rule applied to missing pain VAS at Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    17
    73
    Units: mm
        number (not applicable)
    -1.1
    -41
    No statistical analyses for this end point

    Secondary: Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12

    Close Top of page
    End point title
    Part I: Percentage of Patients With Minimally Important Improvement in CHAQ-DI Score at Week 12 [15]
    End point description
    Percentage of patients who had at least a 0.13 improvement in CHAQ-DI score from Baseline to Week 12. The CHAQ-DI questionnaire consists of 30 questions referring to eight domains; dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain has at least two component questions and if applicable to the patient there are four possible responses (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do).ntent-to-treat Population. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are classified as non-responders. LOCF rule applied to missing CHAQ-DI Scores at Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    37
    75
    Units: percentage of participants
        number (not applicable)
    18.9
    77.3
    No statistical analyses for this end point

    Secondary: Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12

    Close Top of page
    End point title
    Part I: Percentage of Patients With Rash at Baseline Who Are Free From Rash at Week 12 [16]
    End point description
    Percentage of participants who had a rash characteristic of sJIA in the 14 days prior to the baseline visit but no rash characteristic of sJIA in the 14 days preceding the Week 12 visit day. Analysis was performed on participants from the Intent-to-treat population for whom data was available. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are classified as non-responders.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    18
    22
    Units: percentage of participants
        number (not applicable)
    11.1
    63.6
    No statistical analyses for this end point

    Secondary: Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12

    Close Top of page
    End point title
    Part I: Percentage of Patients With Anemia at Baseline With a ≥10 g/L Increase in Hemoglobin at Week 6 and Week 12 [17]
    End point description
    Part I: Percentage of patients who had anemia (hemoglobin <lower level normal based on sex and age) at Baseline and a ≥10 g/L increase in hemoglobin at Week 6 and at Week 12. Analysis was performed on participants from the Intent-to-treat population for whom hemoglobin data available. Patients who withdrew, received escape medication, or for whom the endpoint cannot be determined are classified as non-responders. LOCF rule applied to missing hemoglobin values at Week 6 and Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 6 and Week 12
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per protocol the statistical comparison was made between placebo and all participants who received tocilizumab treatment irrespective of the dosage.
    End point values
    Placebo All Tocilizumab
    Number of subjects analysed
    29
    50
    Units: percentage of participants
    number (not applicable)
        Week 6
    3.4
    88
        Week 12
    3.4
    88
    No statistical analyses for this end point

    Secondary: Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104

    Close Top of page
    End point title
    Part II: Percentage of Participants With JIA ACR70 and JIA ACR90 Responses Week 104
    End point description
    The six JIA ACR components consist of: 1)Physician's global assessment of disease activity, 2)Parent/Patient global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) CHAQ-DI. At an assessment visit a JIA ACR70/90 response in comparison to Baseline is defined as: At least three of the six JIA ACR core components improving by at least 70%/90% and no more than one of the remaining JIA ACR core components worsening by more than 30%. Analysis was performed on participants from the Intent to Treat population who reached the time point plus patients who withdrew because of insufficient therapeutic response and are assumed to have been non-responders.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    All Tocilizumab
    Number of subjects analysed
    75
    Units: percentage of participants
    number (not applicable)
        JIA ACR70 response
    76
        JIA ACR90 response
    61.3
    No statistical analyses for this end point

    Secondary: Part II: Number of Active Joints at Week 104

    Close Top of page
    End point title
    Part II: Number of Active Joints at Week 104
    End point description
    Seventy-one joints were assessed for signs of active arthritis. The mean number of joints with signs of active arthritis is reported. Analysis was performed on participants from the Intent to Treat population who reached this time point. No data imputation is applied and patients with missing data are excluded.
    End point type
    Secondary
    End point timeframe
    Week 104
    End point values
    All Tocilizumab
    Number of subjects analysed
    59
    Units: active joints
        arithmetic mean (standard deviation)
    1.9 ± 3.6
    No statistical analyses for this end point

    Secondary: Part II: Percentage of Participants With no Active Joints at Week 104

    Close Top of page
    End point title
    Part II: Percentage of Participants With no Active Joints at Week 104
    End point description
    Seventy-one joints were assessed for signs of active arthritis. The percentage of participants with no signs of active arthritis is reported. The Intent to Treat population in Part II includes 112 participants who received at least one dose of study drug. Only those participants who reached this time point are included in the analyses.
    End point type
    Secondary
    End point timeframe
    Week 104
    End point values
    All Tocilizumab
    Number of subjects analysed
    76
    Units: percentage of participants
        number (not applicable)
    47.4
    No statistical analyses for this end point

    Secondary: Part II: Percentage of Participants With Inactive Disease at Week 104

    Close Top of page
    End point title
    Part II: Percentage of Participants With Inactive Disease at Week 104
    End point description
    Criteria for Inactive Disease: 1) No joints with active arthritis, 2) No fever, rash, serositis, splenomegaly, hepatomegaly (by physical exam) or generalized lymphadenopathy attributable to systemic juvenile idiopathic arthritis (sJIA), 3) Normal Erythrocyte Sedimentation Rate (<20 mm/hour), 4) Physician’s global assessment of disease activity Visual Analog Scale (VAS) indicates no disease activity (where no disease activity is considered to be a score ≤10 mm on a 100 mm VAS). Participants from the Intent to Treat population who reached time point plus patients who withdrew because of insufficient therapeutic response and are assumed to have been nonresponders.
    End point type
    Secondary
    End point timeframe
    Week 104
    End point values
    All Tocilizumab
    Number of subjects analysed
    75
    Units: percentage of participants
        number (not applicable)
    26.7
    No statistical analyses for this end point

    Secondary: Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104

    Close Top of page
    End point title
    Part II: Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) Score at Week 104
    End point description
    Functional ability is assessed using the CHAQ-DI. The questionnaire consists of 30 questions referring to eight domains; dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain has at least two component questions and if applicable to the patient there are four possible responses (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, 3 = unable to do). The CHAQ-DI score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). Participants from the Intent to Treat population who withdrew have been excluded at post withdrawal visits. n = number of participants analyzed at the specified visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    All Tocilizumab
    Number of subjects analysed
    112
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline (n=112)
    1.68 ± 0.86
        Week 104 (n=57)
    0.55 ± 0.71
    No statistical analyses for this end point

    Secondary: Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104

    Close Top of page
    End point title
    Part II: Percentage of Participants With Oral Corticosteroid Cessation at Week 104
    End point description
    Percentage is based on only those participants who were on oral corticosteroid at baseline and reached a nominal visit day on which dose was calculated. Participants from the Intent to Treat population who withdrew have been excluded at post withdrawal visits.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    All Tocilizumab
    Number of subjects analysed
    42
    Units: percentage of participants
        number (not applicable)
    60
    No statistical analyses for this end point

    Secondary: Part II: Rate of Serious Adverse Events (SAEs), Serious Infection Adverse Events (AEs), Related SAEs, Macrophage Activation Syndrome, AEs Leading to Withdrawal and Deaths Per 100 Patient Years to Week 104

    Close Top of page
    End point title
    Part II: Rate of Serious Adverse Events (SAEs), Serious Infection Adverse Events (AEs), Related SAEs, Macrophage Activation Syndrome, AEs Leading to Withdrawal and Deaths Per 100 Patient Years to Week 104
    End point description
    Rate of SAEs, Rate of Serious Infection AEs, Rate of Related SAEs (remotely, possibly, probably) to Tocilizumab (TCZ), Rate of Macrophage Activation Syndrome, Rate of AEs leading to withdrawal and Rate of deaths per 100 patient years (PY) were calculated using the formula: Number of Patient Events / Duration in study (years) * 100. Multiple occurrences of the same AE in one individual are counted. Safety Population- all participants who received at least one dose of study drug and had 1 post-baseline safety assessment. Includes all safety data in the database up to the week 104 infusion based on the date of randomization for each patient. (Last date was 31 May 2011)
    End point type
    Secondary
    End point timeframe
    104 Weeks
    End point values
    All Tocilizumab
    Number of subjects analysed
    112
    Units: events per 100 patient years
    number (not applicable)
        SAEs
    23.3
        Serious infection AEs
    10.9
        SAEs related to TCZ
    7.4
        Macrophage activation syndrome
    1.5
        AEs leading to withdrawal
    3
        Deaths
    1.5
    No statistical analyses for this end point

    Secondary: Part III: Percentage of Participants with at least 30%, 50%, 70%, and 90% improvement in JIA core set according to ACR

    Close Top of page
    End point title
    Part III: Percentage of Participants with at least 30%, 50%, 70%, and 90% improvement in JIA core set according to ACR
    End point description
    The six JIA ACR components consist of: 1)Physician's global assessment of disease activity, 2)Parent/Patient global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) CHAQ-DI. At an assessment visit a JIA ACR30/50/70/90 response in comparison to Baseline is defined as: At least three of the six JIA ACR core components improving by at least 30%/50%/70%/90% and no more than one of the remaining JIA ACR core components worsening by more than 30%. n = number of participants analyzed for the given parameter at the specified visit. The Part III intent-to-treat (ITT3) population consists of all participants who entered into Part III of the study and received at least one administration of tocilizumab during Part III.
    End point type
    Secondary
    End point timeframe
    Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    42
    47
    Units: percentage of participants
    number (not applicable)
        Week 104 JIA ACR30 (n=42,47)
    100
    100
        Week 104 JIA ACR50 (n=42,47)
    100
    100
        Week 104 JIA ACR70 (n=42,47)
    92.9
    95.7
        Week 104 JIA ACR90 (n=42,47)
    81
    72.3
        Week 116 JIA ACR30 (n=41,45)
    100
    100
        Week 116 JIA ACR50 (n=41,45)
    100
    97.8
        Week 116 JIA ACR70 (n=41,45)
    95.1
    97.8
        Week 116 JIA ACR90 (n=41,45)
    82.9
    80
        Week 128 JIA ACR30 (n=39,41)
    100
    100
        Week 128 JIA ACR50 (n=39,41)
    100
    100
        Week 128 JIA ACR70 (n=39,41)
    97.4
    97.6
        Week 128 JIA ACR90 (n=39,41)
    79.5
    82.9
        Week 140 JIA ACR30 (n=34,37)
    100
    100
        Week 140 JIA ACR50 (n=34,37)
    100
    100
        Week 140 JIA ACR70 (n=34,37)
    100
    94.6
        Week 140 JIA ACR90 (n=34,37)
    73.5
    75.7
        Week 152 JIA ACR30 (n=27,28)
    100
    100
        Week 152 JIA ACR50 (n=27,28)
    100
    100
        Week 152 JIA ACR70 (n=27,28)
    100
    96.4
        Week 152 JIA ACR90 (n=27,28)
    66.7
    78.6
        Week 164 JIA ACR30 (n=27,24)
    100
    100
        Week 164 JIA ACR50 (n=27,24)
    100
    100
        Week 164 JIA ACR70 (n=27,24)
    92.6
    95.8
        Week 164 JIA ACR90 (n=27,24)
    66.7
    75
        Week 176 JIA ACR30 (n=22,22)
    100
    100
        Week 176 JIA ACR50 (n=22,22)
    100
    100
        Week 176 JIA ACR70 (n=22,22)
    100
    95.5
        Week 176 JIA ACR90 (n=22,22)
    63.6
    63.6
        Week 188 JIA ACR30 (n=20,22)
    100
    100
        Week 188 JIA ACR50 (n=20,22)
    100
    100
        Week 188 JIA ACR70 (n=20,22)
    95
    95.5
        Week 188 JIA ACR90 (n=20,22)
    45
    72.7
        Week 200 JIA ACR30 (n=19,19)
    100
    100
        Week 200 JIA ACR50 (n=19,19)
    100
    94.7
        Week 200 JIA ACR70 (n=19,19)
    94.7
    89.5
        Week 200 JIA ACR90 (n=19,19)
    63.2
    78.9
        Week 212 JIA ACR30 (n=18,18)
    100
    100
        Week 212 JIA ACR50 (n=18,18)
    100
    94.4
        Week 212 JIA ACR70 (n=18,18)
    100
    94.4
        Week 212 JIA ACR90 (n=18,18)
    72.2
    77.8
        Week 224 JIA ACR30 (n=17,18)
    100
    100
        Week 224 JIA ACR50 (n=17,18)
    100
    88.9
        Week 224 JIA ACR70 (n=17,18)
    100
    88.9
        Week 224 JIA ACR90 (n=17,18)
    64.7
    83.3
        Week 236 JIA ACR30 (n=16,17)
    100
    100
        Week 236 JIA ACR50 (n=16,17)
    100
    100
        Week 236 JIA ACR70 (n=16,17)
    93.8
    100
        Week 236 JIA ACR90 (n=16,17)
    68.8
    88.2
        Week 248 JIA ACR30 (n=15,17)
    100
    100
        Week 248 JIA ACR50 (n=15,17)
    100
    100
        Week 248 JIA ACR70 (n=15,17)
    86.7
    94.1
        Week 248 JIA ACR90 (n=15,17)
    73.3
    70.6
        Week 260 JIA ACR30 (n=15,15)
    100
    93.3
        Week 260 JIA ACR50 (n=15,15)
    93.3
    93.3
        Week 260 JIA ACR70 (n=15,15)
    86.7
    93.3
        Week 260 JIA ACR90 (n=15,15)
    60
    66.7
    No statistical analyses for this end point

    Secondary: Part III: Percentage of participants who mainitain JIA ACR30, JIA ACR50, JIA ACR70, JIA ACR90 response for 6 months Previous to the specified Week

    Close Top of page
    End point title
    Part III: Percentage of participants who mainitain JIA ACR30, JIA ACR50, JIA ACR70, JIA ACR90 response for 6 months Previous to the specified Week
    End point description
    The six JIA ACR components consist of: 1)Physician's global assessment of disease activity, 2)Parent/Patient global assessment of overall well-being, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) CHAQ-DI. At an assessment visit a JIA ACR30/50/70/90 response in comparison to Baseline is defined as: At least three of the six JIA ACR core components improving by at least 30%/50%/70%/90% and no more than one of the remaining JIA ACR core components worsening by more than 30%. n = number of participants analyzed for the given parameter at the specified visit. Analysis was performed on The Part III ITT3 population. 99999 = Data not available.
    End point type
    Secondary
    End point timeframe
    Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260
    End point values
    All Tocilizumab
    Number of subjects analysed
    89
    Units: percentage of participants
    number (not applicable)
        Week 104 JIA ACR30 (n=89)
    99999
        Week 104 JIA ACR50 (n=89)
    99999
        Week 104 JIA ACR70 (n=89)
    99999
        Week 104 JIA ACR90 (n=89)
    99999
        Week 116 JIA ACR 30 (n=86)
    99999
        Week 116 JIA ACR 50 (n=86)
    99999
        Week 116 JIA ACR 70 (n=86)
    99999
        Week 116 JIA ACR 90 (n=86)
    99999
        Week 128 JIA ACR 30 (n=80)
    100
        Week 128 JIA ACR 50 (n=80)
    98.8
        Week 128 JIA ACR 70 (n=80)
    91.3
        Week 128 JIA ACR 90 (n=80)
    68.8
        Week 140 JIA ACR30 (n=71)
    100
        Week 140 JIA ACR50 (n=71)
    98.6
        Week 140 JIA ACR70 (n=71)
    93
        Week 140 JIA ACR90 (n=71)
    66.2
        Week 152 JIA ACR30 (n=55)
    100
        Week 152 JIA ACR50 (n=55)
    100
        Week 152 JIA ACR70 (n=55)
    94.5
        Week 152 JIA ACR90 (n=55)
    60
        Week 164 JIA ACR30 (n=51)
    100
        Week 164 JIA ACR50 (n=51)
    100
        Week 164 JIA ACR70 (n=51)
    92.2
        Week 164 JIA ACR90 (n=51)
    56.9
        Week 176 JIA ACR30 (n=44)
    100
        Week 176 JIA ACR50 (n=44)
    100
        Week 176 JIA ACR70 (n=44)
    88.6
        Week 176 JIA ACR90 (n=44)
    52.3
        Week 188 JIA ACR30 (n=42)
    100
        Week 188 JIA ACR50 (n=42)
    100
        Week 188 JIA ACR70 (n=42)
    88.1
        Week 188 JIA ACR90 (n=42)
    50
        Week 200 JIA ACR30 (n=38)
    100
        Week 200 JIA ACR50 (n=38)
    97.4
        Week 200 JIA ACR70 (n=38)
    86.8
        Week 200 JIA ACR90 (n=38)
    52.6
        Week 212 JIA ACR30 (n=36)
    100
        Week 212 JIA ACR50 (n=36)
    97.2
        Week 212 JIA ACR70 (n=36)
    88.9
        Week 212 JIA ACR90 (n=36)
    55.6
        Week 224 JIA ACR30 (n=35)
    100
        Week 224 JIA ACR50 (n=35)
    94.3
        Week 224 JIA ACR70 (n=35)
    91.4
        Week 224 JIA ACR90 (n=35)
    68.6
        Week 236 JIA ACR30 (n=33)
    100
        Week 236 JIA ACR50 (n=33)
    93.9
        Week 236 JIA ACR70 (n=33)
    90.9
        Week 236 JIA ACR90 (n=33)
    72.7
        Week 248 JIA ACR30 (n=32)
    100
        Week 248 JIA ACR50 (n=32)
    93.8
        Week 248 JIA ACR70 (n=32)
    87.5
        Week 248 JIA ACR90 (n=32)
    65.6
        Week 260 JIA ACR30 (n=30)
    96.7
        Week 260 JIA ACR50 (n=30)
    93.3
        Week 260 JIA ACR70 (n=30)
    80
        Week 260 JIA ACR90 (n=30)
    56.7
    No statistical analyses for this end point

    Secondary: Part III: Doses of Oral Corticosteroids (CS)

    Close Top of page
    End point title
    Part III: Doses of Oral Corticosteroids (CS)
    End point description
    Oral corticosteroid values summarized are based on average daily dose on the nominal study day. The prednisone equivalent is used in calculation of oral corticosteroid dose. Participants who withdrew are excluded at the visit of withdrawal and all subsequent visits. n=number of participants contributing to the specific statistic.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    53
    59
    Units: mg/kg/day
    arithmetic mean (standard deviation)
        Baseline (n=53,59)
    0.203 ± 0.1572
    0.356 ± 0.1397
        Week 104 (n=45,48)
    0.02 ± 0.0455
    0.047 ± 0.0869
        Week 116 (n=42,46)
    0.022 ± 0.0464
    0.046 ± 0.0831
        Week 128 (n=41,42)
    0.022 ± 0.0449
    0.058 ± 0.1635
        Week 140 (n=34,38)
    0.031 ± 0.0625
    0.051 ± 0.1112
        Week 152 (n=28,31)
    0.021 ± 0.0388
    0.06 ± 0.1125
        Week 164 (n=28,25)
    0.018 ± 0.0349
    0.068 ± 0.1179
        Week 176 (n=25,23)
    0.019 ± 0.0383
    0.073 ± 0.1327
        Week 188 (n=21,22)
    0.02 ± 0.0366
    0.075 ± 0.1275
        Week 200 (n=20,20)
    0.017 ± 0.0284
    0.083 ± 0.1397
        Week 212 (n=19,19)
    0.016 ± 0.0274
    0.077 ± 0.1449
        Week 224 (n=18,19)
    0.017 ± 0.0279
    0.075 ± 0.1399
        Week 236 (n=17,18)
    0.018 ± 0.0283
    0.077 ± 0.1436
        Week 248 (n=16,18)
    0.02 ± 0.029
    0.076 ± 0.1429
        Week 260 (n=16,18)
    0.019 ± 0.0282
    0.079 ± 0.1486
    No statistical analyses for this end point

    Secondary: Part III: Percentage of Participants on Corticosteroids at Baseline Able to Discontinue Corticosteroids by Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260

    Close Top of page
    End point title
    Part III: Percentage of Participants on Corticosteroids at Baseline Able to Discontinue Corticosteroids by Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260
    End point description
    Values summarized are based on average daily dose on the nominal study day. The prednisone equivalent is used in calculation of oral corticosteroid dose. Participants who withdrew are excluded at the timepoint of this event and at all subsequent visits. Baseline considered first dose of study treatment. Data presented up to entry into the Alternative Dosing Schedule. ITT3 population; n=number of participants contributing to the specific statistic.
    End point type
    Secondary
    End point timeframe
    Weeks 104,116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    38
    46
    Units: percentage of participants
    number (not applicable)
        Week 104 (n=38,46)
    66
    67
        Week 116 (n=36,44)
    67
    68
        Week 128 (n=35,40)
    69
    70
        Week 140 (n=31,36)
    68
    67
        Week 152 (n=25,30)
    64
    57
        Week 164 (n=25,24)
    68
    58
        Week 176 (n=22,22)
    68
    64
        Week 188 (n=18,21)
    61
    57
        Week 200 (n=17,20)
    59
    60
        Week 212 (n=16,19)
    56
    63
        Week 224 (n=15,19)
    53
    63
        Week 236 (n=14,18)
    50
    61
        Week 248 (n=13,18)
    46
    61
        Week 260 (n=13,18)
    46
    61
    No statistical analyses for this end point

    Secondary: Part III: Percentage of Participants with a ≥20/50/75/90% Decrease from Baseline in Oral Corticosteroid Dose at Visits

    Close Top of page
    End point title
    Part III: Percentage of Participants with a ≥20/50/75/90% Decrease from Baseline in Oral Corticosteroid Dose at Visits
    End point description
    Values summarized are based on average daily dose on the nominal study day. The prednisone equivalent is used in calculation of oral corticosteroid dose. Participants who withdrew are excluded at the timepoint of this event and at all subsequent visits. Baseline considered first dose of study treatment. ITT3 population; n=number of participants contributing to the specific statistic.
    End point type
    Secondary
    End point timeframe
    Every 2 weeks from Week 104 to 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    38
    46
    Units: percentage of participants
    number (not applicable)
        Week 104 ≥20% decrease (n=38,46)
    100
    97.8
        Week 104 ≥50% decrease (n=38,46)
    94.7
    91.3
        Week 104 ≥75% decrease (n=38,46)
    84.2
    82.6
        Week 104 ≥90% decrease (n=38,46)
    71.1
    71.7
        Week 106 ≥20% decrease (n=37,46)
    100
    97.8
        Week 106 ≥50% decrease (n=37,46)
    91.9
    91.3
        Week 106 ≥75% decrease (n=37,46)
    83.8
    82.6
        Week 106 ≥90% decrease (n=37,46)
    70.3
    71.7
        Week 108 ≥20% decrease (n=37,45)
    100
    100
        Week 108 ≥50% decrease (n=37,45)
    89.2
    91.1
        Week 108 ≥75% decrease (n=37,45)
    81.1
    84.4
        Week 108 ≥90% decrease (n=37,45)
    70.3
    73.3
        Week 110 ≥20% decrease (n=36,44)
    100
    100
        Week 110 ≥50% decrease (n=36,44)
    88.9
    93.2
        Week 110 ≥75% decrease (n=36,44)
    80.6
    84.1
        Week 110 ≥90% decrease (n=36,44)
    72.2
    75
        Week 112 ≥20% decrease (n=36,44)
    100
    100
        Week 112 ≥50% decrease (n=36,44)
    88.9
    95.5
        Week 112 ≥75% decrease (n=36,44)
    80.6
    81.8
        Week 112 ≥90% decrease (n=36,44)
    72.2
    75
        Week 114 ≥20% decrease (n=36,44)
    100
    100
        Week 114 ≥50% decrease (n=36,44)
    88.9
    95.5
        Week 114 ≥75% decrease (n=36,44)
    80.6
    79.5
        Week 114 ≥90% decrease (n=36,44)
    72.2
    72.7
        Week 116 ≥20% decrease (n=35,44)
    100
    100
        Week 116 ≥50% decrease (n=35,44)
    91.4
    93.2
        Week 116 ≥75% decrease (n=35,44)
    80
    79.5
        Week 116 ≥90% decrease (n=35,44)
    71.4
    72.7
        Week 118 ≥20% decrease (n=35,43)
    100
    100
        Week 118 ≥50% decrease (n=35,43)
    88.6
    93
        Week 118 ≥75% decrease (n=35,43)
    80
    81.4
        Week 118 ≥90% decrease (n=35,43)
    71.4
    74.4
        Week 120 ≥20% decrease (n=35,43)
    100
    100
        Week 120 ≥50% decrease (n=35,43)
    88.6
    93
        Week 120 ≥75% decrease (n=35,43)
    80
    83.7
        Week 120 ≥90% decrease (n=35,43)
    74.3
    76.7
        Week 122 ≥20% decrease (n=35,43)
    97.1
    100
        Week 122 ≥50% decrease (n=35,43)
    88.6
    93
        Week 122 ≥75% decrease (n=35,43)
    77.1
    81.4
        Week 122 ≥90% decrease (n=35,43)
    74.3
    74.4
        Week 124 ≥20% decrease (n=35,43)
    100
    100
        Week 124 ≥50% decrease (n=35,43)
    94.3
    93
        Week 124 ≥75% decrease (n=35,43)
    80
    83.7
        Week 124 ≥90% decrease (n=35,43)
    77.1
    74.4
        Week 126 ≥20% decrease (n=35,43)
    100
    100
        Week 126 ≥50% decrease (n=35,43)
    94.3
    90.7
        Week 126 ≥75% decrease (n=35,43)
    80
    81.4
        Week 126 ≥90% decrease (n=35,43)
    77.1
    74.4
        Week 128 ≥20% decrease (n=35,39)
    100
    97.4
        Week 128 ≥50% decrease (n=35,39)
    91.4
    89.7
        Week 128 ≥75% decrease (n=35,39)
    80
    82.1
        Week 128 ≥90% decrease (n=35,39)
    77.1
    71.8
        Week 130 ≥20% decrease (n=35,39)
    100
    97.4
        Week 130 ≥50% decrease (n=35,39)
    91.4
    89.7
        Week 130 ≥75% decrease (n=35,39)
    80
    87.2
        Week 130 ≥90% decrease (n=35,39)
    80
    74.4
        Week 132 ≥20% decrease (n=35,39)
    100
    97.4
        Week 132 ≥50% decrease (n=35,39)
    91.4
    87.2
        Week 132 ≥75% decrease (n=35,39)
    80
    84.6
        Week 132 ≥90% decrease (n=35,39)
    80
    71.8
        Week 134 ≥20% decrease (n=35,39)
    94.3
    97.4
        Week 134 ≥50% decrease (n=35,39)
    88.6
    87.2
        Week 134 ≥75% decrease (n=35,39)
    77.1
    84.6
        Week 134 ≥90% decrease (n=35,39)
    77.1
    71.8
        Week 136 ≥20% decrease (n=34,39)
    97.1
    97.4
        Week 136 ≥50% decrease (n=34,39)
    91.2
    89.7
        Week 136 ≥75% decrease (n=34,39)
    76.5
    84.6
        Week 136 ≥90% decrease (n=34,39)
    76.5
    71.8
        Week 138 ≥20% decrease (n=34,39)
    94.1
    97.4
        Week 138 ≥50% decrease (n=34,39)
    88.2
    89.7
        Week 138 ≥75% decrease (n=34,39)
    76.5
    84.6
        Week 138 ≥90% decrease (n=34,39)
    76.5
    71.8
        Week 140 ≥20% decrease (n=29,36)
    93.1
    97.2
        Week 140 ≥50% decrease (n=29,36)
    86.2
    88.9
        Week 140 ≥75% decrease (n=29,36)
    72.4
    83.3
        Week 140 ≥90% decrease (n=29,36)
    72.4
    72.2
        Week 142 ≥20% decrease (n=29,36)
    93.1
    97.2
        Week 142 ≥50% decrease (n=29,36)
    86.2
    88.9
        Week 142 ≥75% decrease (n=29,36)
    72.4
    83.3
        Week 142 ≥90% decrease (n=29,36)
    69
    72.2
        Week 144 ≥20% decrease (n=28,36)
    92.9
    97.2
        Week 144 ≥50% decrease (n=28,36)
    89.3
    88.9
        Week 144 ≥75% decrease (n=28,36)
    71.4
    83.3
        Week 144 ≥90% decrease (n=28,36)
    67.9
    72.2
        Week 146 ≥20% decrease (n=28,36)
    96.4
    97.2
        Week 146 ≥50% decrease (n=28,36)
    92.9
    86.1
        Week 146 ≥75% decrease (n=28,36)
    75
    80.6
        Week 146 ≥90% decrease (n=28,36)
    71.4
    66.7
        Week 148 ≥20% decrease (n=27,35)
    100
    97.1
        Week 148 ≥50% decrease (n=27,35)
    96.3
    85.7
        Week 148 ≥75% decrease (n=27,35)
    77.8
    80
        Week 148 ≥90% decrease (n=27,35)
    74.1
    65.7
        Week 150 ≥20% decrease (n=25,35)
    100
    97.1
        Week 150 ≥50% decrease (n=25,35)
    96
    88.6
        Week 150 ≥75% decrease (n=25,35)
    76
    80
        Week 150 ≥90% decrease (n=25,35)
    76
    68.6
        Week 152 ≥20% decrease (n=25,27)
    100
    96.3
        Week 152 ≥50% decrease (n=25,27)
    96
    85.2
        Week 152 ≥75% decrease (n=25,27)
    76
    77.8
        Week 152 ≥90% decrease (n=25,27)
    76
    63
        Week 154 ≥20% decrease (n=25,27)
    100
    96.3
        Week 154 ≥50% decrease (n=25,27)
    96
    88.9
        Week 154 ≥75% decrease (n=25,27)
    76
    77.8
        Week 154 ≥90% decrease (n=25,27)
    76
    70.4
        Week 156 ≥20% decrease (n=25,27)
    100
    96.3
        Week 156 ≥50% decrease (n=25,27)
    96
    85.2
        Week 156 ≥75% decrease (n=25,27)
    76
    77.8
        Week 156 ≥90% decrease (n=25,27)
    76
    70.4
        Week 158 ≥20% decrease (n=25,27)
    100
    96.3
        Week 158 ≥50% decrease (n=25,27)
    96
    88.9
        Week 158 ≥75% decrease (n=25,27)
    76
    77.8
        Week 158 ≥90% decrease (n=25,27)
    76
    70.4
        Week 160 ≥20% decrease (n=25,27)
    100
    96.3
        Week 160 ≥50% decrease (n=25,27)
    96
    85.2
        Week 160 ≥75% decrease (n=25,27)
    76
    77.8
        Week 160 ≥90% decrease (n=25,27)
    76
    70.4
        Week 162 ≥20% decrease (n=25,27)
    100
    96.3
        Week 162 ≥50% decrease (n=25,27)
    96
    81.5
        Week 162 ≥75% decrease (n=25,27)
    76
    77.8
        Week 162 ≥90% decrease (n=25,27)
    76
    70.4
        Week 164 ≥20% decrease (n=24,24)
    100
    95.8
        Week 164 ≥50% decrease (n=24,24)
    95.8
    83.3
        Week 164 ≥75% decrease (n=24,24)
    75
    75
        Week 164 ≥90% decrease (n=24,24)
    75
    70.8
        Week 166 ≥20% decrease (n=24,22)
    100
    95.5
        Week 166 ≥50% decrease (n=24,22)
    95.8
    81.8
        Week 166 ≥75% decrease (n=24,22)
    75
    72.7
        Week 166 ≥90% decrease (n=24,22)
    75
    68.2
        Week 168 ≥20% decrease (n=24,22)
    100
    95.5
        Week 168 ≥50% decrease (n=24,22)
    95.8
    81.8
        Week 168 ≥75% decrease (n=24,22)
    75
    72.7
        Week 168 ≥90% decrease (n=24,22)
    75
    68.2
        Week 170 ≥20% decrease (n=22,22)
    100
    90.9
        Week 170 ≥50% decrease (n=22,22)
    95.5
    81.8
        Week 170 ≥75% decrease (n=22,22)
    77.3
    72.7
        Week 170 ≥90% decrease (n=22,22)
    77.3
    68.2
        Week 172 ≥20% decrease (n=22,22)
    100
    90.9
        Week 172 ≥50% decrease (n=22,22)
    95.5
    90.9
        Week 172 ≥75% decrease (n=22,22)
    77.3
    72.7
        Week 172 ≥90% decrease (n=22,22)
    77.3
    68.2
        Week 174 ≥20% decrease (n=22,22)
    100
    90.9
        Week 174 ≥50% decrease (n=22,22)
    95.5
    90.9
        Week 174 ≥75% decrease (n=22,22)
    77.3
    72.7
        Week 174 ≥90% decrease (n=22,22)
    77.3
    68.2
        Week 176 ≥20% decrease (n=19,22)
    100
    90.9
        Week 176 ≥50% decrease (n=19,22)
    94.7
    90.9
        Week 176 ≥75% decrease (n=19,22)
    73.7
    72.7
        Week 176 ≥90% decrease (n=19,22)
    73.7
    68.2
        Week 178 ≥20% decrease (n=19,22)
    100
    90.9
        Week 178 ≥50% decrease (n=19,22)
    94.7
    90.9
        Week 178 ≥75% decrease (n=19,22)
    73.7
    72.7
        Week 178 ≥90% decrease (n=19,22)
    73.7
    68.2
        Week 180 ≥20% decrease (n=19,22)
    100
    90.9
        Week 180 ≥50% decrease (n=19,22)
    94.7
    90.9
        Week 180 ≥75% decrease (n=19,22)
    73.7
    68.2
        Week 180 ≥90% decrease (n=19,22)
    73.7
    63.6
        Week 182 ≥20% decrease (n=18,22)
    100
    90.9
        Week 182 ≥50% decrease (n=18,22)
    94.4
    90.9
        Week 182 ≥75% decrease (n=18,22)
    72.2
    68.2
        Week 182 ≥90% decrease (n=18,22)
    72.2
    63.6
        Week 184 ≥20% decrease (n=18,22)
    100
    90.9
        Week 184 ≥50% decrease (n=18,22)
    94.4
    86.4
        Week 184 ≥75% decrease (n=18,22)
    72.2
    68.2
        Week 184 ≥90% decrease (n=18,22)
    72.2
    63.6
        Week 186 ≥20% decrease (n=18,22)
    100
    90.9
        Week 186 ≥50% decrease (n=18,22)
    94.4
    90.9
        Week 186 ≥75% decrease (n=18,22)
    72.2
    68.2
        Week 186 ≥90% decrease (n=18,22)
    72.2
    63.6
        Week 188 ≥20% decrease (n=18,21)
    100
    90.5
        Week 188 ≥50% decrease (n=18,21)
    94.4
    90.5
        Week 188 ≥75% decrease (n=18,21)
    72.2
    71.4
        Week 188 ≥90% decrease (n=18,21)
    72.2
    61.9
        Week 190 ≥20% decrease (n=18,21)
    100
    95.2
        Week 190 ≥50% decrease (n=18,21)
    94.4
    85.7
        Week 190 ≥75% decrease (n=18,21)
    72.2
    66.7
        Week 190 ≥90% decrease (n=18,21)
    72.2
    61.9
        Week 192 ≥20% decrease (n=18,21)
    100
    95.2
        Week 192 ≥50% decrease (n=18,21)
    94.4
    81
        Week 192 ≥75% decrease (n=18,21)
    72.2
    66.7
        Week 192 ≥90% decrease (n=18,21)
    72.2
    61.9
        Week 194 ≥20% decrease (n=18,20)
    100
    95
        Week 194 ≥50% decrease (n=18,20)
    94.4
    80
        Week 194 ≥75% decrease (n=18,20)
    72.2
    70
        Week 194 ≥90% decrease (n=18,20)
    72.2
    65
        Week 196 ≥20% decrease (n=18,20)
    100
    90
        Week 196 ≥50% decrease (n=18,20)
    94.4
    80
        Week 196 ≥75% decrease (n=18,20)
    72.2
    70
        Week 196 ≥90% decrease (n=18,20)
    72.2
    65
        Week 198 ≥20% decrease (n=18,20)
    100
    90
        Week 198 ≥50% decrease (n=18,20)
    94.4
    80
        Week 198 >75% decrease (n=18,20)
    72.2
    75
        Week 198 ≥90% decrease (n=18,20)
    72.2
    65
        Week 200 ≥20% decrease (n=17,20)
    100
    90
        Week 200 ≥50% decrease (n=17,20)
    94.1
    85
        Week 200 ≥75% decrease (n=17,20)
    76.5
    75
        Week 200 ≥90% decrease (n=17,20)
    70.6
    65
        Week 202 ≥20% decrease (n=17,20)
    100
    90
        Week 202 ≥50% decrease (n=17,20)
    94.1
    85
        Week 202 ≥75% decrease (n=17,20)
    76.5
    75
        Week 202 ≥90% decrease (n=17,20)
    70.6
    65
        Week 204 ≥20% decrease (n=17,20)
    100
    90
        Week 204 ≥50% decrease (n=17,20)
    94.1
    85
        Week 204 ≥70% decrease (n=17,20)
    76.5
    75
        Week 204 ≥90% decrease (n=17,20)
    70.6
    65
        Week 206 ≥20% decrease (n=16,20)
    100
    85
        Week 206 ≥50% decrease (n=16,20)
    93.8
    75
        Week 206 ≥75% decrease (n=16,20)
    75
    75
        Week 206 ≥90% decrease (n=16,20)
    68.8
    70
        Week 208 ≥20% decrease (n=16,20)
    100
    90
        Week 208 ≥50% decrease (n=16,20)
    93.8
    80
        Week 208 ≥75% decrease (n=16,20
    75
    75
        Week 208 ≥90% decrease (n=16,20)
    68.8
    70
        Week 210 ≥20% decrease (n=16,19)
    100
    89.5
        Week 210 ≥50% decrease (n=16,19)
    93.8
    84.2
        Week 210 ≥75% decrease (n=16,19)
    81.3
    78.9
        Week 210 ≥90% decrease (n=16,19)
    75
    73.7
        Week 212 ≥20% decrease (n=15,19)
    100
    89.5
        Week 212 ≥50% decrease (n=15,19)
    93.3
    84.2
        Week 212 ≥75% decrease (n=15,19)
    73.3
    78.9
        Week 212 ≥90% decrease (n=15,19)
    73.3
    73.7
        Week 214 ≥20% decrease (n=15,19)
    100
    89.5
        Week 214 ≥50% decrease (n=15,19)
    93.3
    84.2
        Week 214 ≥75% decrease (n=15,19)
    73.3
    78.9
        Week 214 ≥90% decrease (n=15,19)
    73.3
    73.7
        Week 216 ≥20% decrease (n=15,19)
    100
    94.7
        Week 216 ≥50% decrease (n=15,19)
    93.3
    84.2
        Week 216 ≥75% decrease (n=15,19)
    73.3
    78.9
        Week 216 ≥90% decrease (n=15,19)
    73.3
    73.7
        Week 218 ≥20% decrease (n=15,19)
    100
    89.5
        Week 218 ≥50% decrease (n=15,19)
    93.3
    84.2
        Week 218 ≥75% decrease (n=15,19)
    80
    78.9
        Week 218 ≥90% decrease (n=15,19)
    73.3
    73.7
        Week 220 ≥20% decrease (n=15,19)
    100
    89.5
        Week 220 ≥50% decrease (n=15,19)
    93.3
    84.2
        Week 220 ≥75% decrease (n=15,19)
    80
    78.9
        Week 220 ≥90% decrease (n=15,19)
    73.3
    73.7
        Week 222 ≥20% decrease (n=15,19)
    100
    89.5
        Week 222 ≥50% decrease (n=15,19)
    93.3
    84.2
        Week 222 ≥75% decrease (n=15,19)
    80
    78.9
        Week 222 ≥90% decrease (n=15,19)
    73.3
    73.7
        Week 224 ≥20% decrease (n=15,19)
    100
    89.5
        Week 224 ≥50% decrease (n=15,19)
    93.3
    84.2
        Week 224 ≥75% decrease (n=15,19)
    80
    78.9
        Week 224 ≥90% decrease (n=15,19)
    73.3
    73.7
        Week 226 ≥20% decrease (n=14,19)
    100
    89.5
        Week 226 ≥50% decrease (n=14,19)
    92.9
    84.2
        Week 226 ≥75% decrease (n=14,19)
    78.6
    78.9
        Week 226 ≥90% decrease (n=14,19)
    71.4
    73.7
        Week 228 ≥20% decrease (n=14,19)
    100
    89.5
        Week 228 ≥50% decrease (n=14,19)
    92.9
    89.5
        Week 228 ≥75% decrease (n=14,19)
    78.6
    78.9
        Week 228 ≥90% decrease (n=14,19)
    71.4
    73.7
        Week 230 ≥20% decrease (n=14,19)
    100
    89.5
        Week 230 ≥50% decrease (n=14,19)
    92.9
    89.5
        Week 230 ≥75% decrease (n=14,19)
    78.6
    78.9
        Week 230 ≥90% decrease (n=14,19)
    71.4
    73.7
        Week 232 ≥20% decrease (n=14,18)
    100
    88.9
        Week 232 ≥50% decrease (n=14,18)
    92.9
    88.9
        Week 232 ≥75% decrease (n=14,18)
    78.6
    77.8
        Week 232 ≥90% decrease (n=14,18)
    71.4
    72.2
        Week 234 ≥20% decrease (n=14,18)
    100
    88.9
        Week 234 ≥50% decrease (n=14,18)
    92.9
    88.9
        Week 234 ≥75% decrease (n=14,18)
    78.6
    77.8
        Week 234 ≥90% decrease (n=14,18)
    71.4
    72.2
        Week 236 ≥20% decrease (n=14,18)
    100
    94.4
        Week 236 ≥50% decrease (n=14,18)
    92.9
    88.9
        Week 236 ≥75% decrease (n=14,18)
    78.6
    77.8
        Week 236 ≥90% decrease (n=14,18)
    71.4
    72.2
        Week 238 ≥20% decrease (n=14,18)
    100
    94.4
        Week 238 ≥50% decrease (n=14,18)
    92.9
    88.9
        Week 238 ≥75% decrease (n=14,18)
    78.6
    77.8
        Week 238 ≥90% decrease (n=14,18)
    71.4
    72.2
        Week 240 ≥20% decrease (n=13,18)
    100
    94.4
        Week 240 ≥50% decrease (n=13,18)
    92.3
    88.9
        Week 240 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 240 ≥90% decrease (n=13,18)
    69.2
    72.2
        Week 242 ≥20% decrease (n=13,18)
    100
    94.4
        Week 242 ≥50% decrease (n=13,18)
    92.3
    88.9
        Week 242 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 242 ≥90% decrease (n=13,18)
    69.2
    72.2
        Week 244 ≥20% decrease (n=13,18)
    100
    94.4
        Week 244 ≥50% decrease (n=13,18)
    92.3
    88.9
        Week 244 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 244 ≥90% decrease (n=13,18)
    69.2
    72.2
        Week 246 ≥20% decrease (n=13,18)
    100
    94.4
        Week 246 ≥50% decrease (n=13,18)
    92.3
    88.9
        Week 246 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 246 ≥90% decrease (n=13,18)
    69.2
    72.2
        Week 248 ≥20% decrease (n=13,18)
    100
    94.4
        Week 248 ≥50% decrease (n=13,18)
    92.3
    88.9
        Week 248 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 248 ≥90% decrease (n=13,18)
    69.2
    72.2
        Week 250 ≥20% decrease (n=13,18)
    100
    94.4
        Week 250 ≥50% decrease (n=13,18)
    92.3
    83.3
        Week 250 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 250 ≥90% decrease (n=13,18)
    69.2
    72.2
        Week 252 ≥20% decrease (n=13,18)
    100
    94.4
        Week 252 ≥50% decrease (n=13,18)
    92.3
    83.3
        Week 252 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 252 ≥90% decrease (n=13,18)
    69.2
    72.2
        Week 254 ≥20% decrease (n=13,18)
    100
    94.4
        Week 254 ≥50% decrease (n=13,18)
    92.3
    83.3
        Week 254 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 254 ≥90% decrease (n=13,18)
    69.2
    72.2
        Week 256 ≥20% decrease (n=13,18)
    100
    94.4
        Week 256 ≥50% decrease (n=13,18)
    92.3
    83.3
        Week 256 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 256 ≥90% decrease (n=13,18)
    69.2
    72.2
        Week 258 ≥20% decrease (n=13,18)
    100
    94.4
        Week 258 ≥50% decrease (n=13,18)
    92.3
    83.3
        Week 258 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 258 ≥90% decrease (n=13,18)
    69.2
    72.2
        Week 260 ≥20% decrease (n=13,18)
    100
    94.4
        Week 260 ≥50% decrease (n=13,18)
    92.3
    88.9
        Week 260 ≥75% decrease (n=13,18)
    76.9
    77.8
        Week 260 ≥90% decrease (n=13,18)
    69.2
    72.2
    No statistical analyses for this end point

    Secondary: Part III: Percentage of Participants with Inactive Disease

    Close Top of page
    End point title
    Part III: Percentage of Participants with Inactive Disease
    End point description
    Participants who previously withdrew are excluded. Responders are participants who met all of the following criteria for inactive disease at the visit assessment day: i. Number of active joints = 0. ii. Absence of lymphadenopathy, hepatomegaly or splenomegaly in the nearest non-missing physical examination prior to or after the week assessment day. This could include results outside of the time window. iii. Absence of symptomatic serositis adverse event. iv. In the 14 days preceding the week assessment day no fever (temperature >=37.5 degrees C) or rash characteristic of sJIA. v. Normal ESR as defined by an ESR <20 mm/hr regardless of age and sex. vi. Physician global assessment VAS <=10. LOCF rule applied to missing number of active joints, ESR and Physician global assessment VAS. Data presented up to the point of entry into the Alternative Dosing Schedule. ITT3 population; n=number of participants contributing to the specific statistic.
    End point type
    Secondary
    End point timeframe
    Weeks 104, 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    42
    47
    Units: percentage of participants
    number (not applicable)
        Week 104 (n=42,47)
    45.2
    46.8
        Week 116 (n=41,46)
    48.8
    43.5
        Week 128 (n=40,43)
    55
    48.8
        Week 140 (n=38,40)
    55.3
    45
        Week 152 (n=27,35)
    33.3
    54.3
        Week 164 (n=27,25)
    37
    28
        Week 176 (n=24,22)
    41.7
    36.4
        Week 188 (n=21,22)
    23.8
    31.8
        Week 200 (n=19,21)
    42.1
    14.3
        Week 212 (n=18,18 )
    55.6
    44.4
        Week 224 (n=17,18)
    47.1
    44.4
        Week 236 (n=16,17)
    43.8
    29.4
        Week 248 (n=15,17)
    26.7
    41.2
        Week 260 (n=15,15)
    46.7
    6.7
    No statistical analyses for this end point

    Secondary: Part III: Percentage of Participants in Clinical Remission

    Close Top of page
    End point title
    Part III: Percentage of Participants in Clinical Remission
    End point description
    Patients who previously withdrew are excluded. Responders are patients who met all of the following criteria for inactive disease at all visits in 6 months (180 days) prior to and including the visit assessment day: i. Number of active joints = 0. ii. Absence of lymphadenopathy, hepatomegaly or splenomegaly in the nearest non-missing physical examination prior to or after the week assessment day. This could include results outside of the time window. iii. Absence of symptomatic serositis adverse event. iv. In the 14 days preceding the week assessment day no fever (temperature >=37.5 C) or rash characteristic of sJIA. v. Normal ESR as defined by an ESR <20 mm/hr regardless of age and sex. iv. Physician global assessment VAS <=10. LOCF rule applied to missing number of active joints, ESR and Physician global assessment VAS. ESR = Erythrocyte Sedimentation Rate. VAS = Visual Analogue Scale. Data presented up to the point of entry into the Alternative Dosing Schedule. ITT3 population.
    End point type
    Secondary
    End point timeframe
    Weeks 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248 and 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    41
    47
    Units: percentage of participants
    number (not applicable)
        Week 116 (n=41,46)
    14.6
    17.4
        Week 128 (n=40,43)
    32.5
    23.3
        Week 140 (n=38,40)
    34.2
    25
        Week 152 (n=27,35)
    25.9
    25.7
        Week 164 (n=27,25)
    22.2
    16
        Week 176 (n=24,22)
    16.7
    13.6
        Week 188 (n=21,22)
    14.3
    9.1
        Week 200 (n=19,21)
    15.8
    4.8
        Week 212 (n=18,18)
    16.7
    5.6
        Week 224 (n=17,18)
    29.4
    11.1
        Week 236 (n=16,17)
    25
    29.4
        Week 248 (n=15,17)
    13.3
    23.5
        Week 260 (n=15,15)
    13.3
    6.7
    No statistical analyses for this end point

    Secondary: Part III: Percentage of Participants on CSs at Baseline in Clinical Remission off all Oral CSs for 6 Months Prior to Specific Weeks

    Close Top of page
    End point title
    Part III: Percentage of Participants on CSs at Baseline in Clinical Remission off all Oral CSs for 6 Months Prior to Specific Weeks
    End point description
    There were 4 levels of clinical remission defined while the patient remained on tocilizumab as defined below.. After level 1, each successive level required that all the previous level criteria be met: Level 1: inactive disease criteria have been met at all assessments in the last 6 months (180 days) preceding the timepoint assessment day Level 2: level 1 criteria and no oral corticosteroids received in the last 6 months (180 days) preceding the timepoint assessment day. Level 3: level 2 criteria and no methotrexate received in the last 6 months (180 days) preceding the timepoint assessment day Level 4: level 3 criteria and no NSAIDs received for sJIA in the last 6 months (180 days) preceding the timepoint assessment day. ITT3 population; n=number of participants contributing to the specific statistic.
    End point type
    Secondary
    End point timeframe
    Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    41
    46
    Units: percentage of participants
    number (not applicable)
        Week 116 (n=41,46)
    12.2
    17.4
        Week 128 (n=40,43)
    32.5
    20.9
        Week 140 (n=38,40)
    28.9
    20
        Week 152 (n=27,35)
    18.5
    20
        Week 164 (n=27,25)
    18.5
    12
        Week 176 (n=24,22)
    16.7
    9.1
        Week 188 (n=21,22)
    14.3
    4.5
        Week 200 (n=19,21)
    10.5
    4.8
        Week 212 (n=18,18)
    11.1
    5.6
        Week 224 (n=17,18)
    23.5
    11.1
        Week 236 (n=16,17)
    25
    23.5
        Week 248 (n=15,17)
    6.7
    17.6
        Week 260 (n=15,15)
    6.7
    6.7
    No statistical analyses for this end point

    Secondary: Part III: Percentage of Participants on Methotrexate (MTX) at Baseline in Clinical Remission off Corticosteroids and MTX for 6 Months Prior to Specified Weeks

    Close Top of page
    End point title
    Part III: Percentage of Participants on Methotrexate (MTX) at Baseline in Clinical Remission off Corticosteroids and MTX for 6 Months Prior to Specified Weeks
    End point description
    There were 4 levels of clinical remission defined while the patient remained on tocilizumab as defined below.. After level 1, each successive level required that all the previous level criteria be met: Level 1: inactive disease criteria have been met at all assessments in the last 6 months (180 days) preceding the timepoint assessment day Level 2: level 1 criteria and no oral corticosteroids received in the last 6 months (180 days) preceding the timepoint assessment day Level 3: level 2 criteria and no methotrexate received in the last 6 months (180 days) preceding the timepoint assessment day Level 4: level 3 criteria and no NSAIDs received for sJIA in the last 6 months (180 days) preceding the timepoint assessment day. ITT3 population; n=number of participants contributing to the specific statistic
    End point type
    Secondary
    End point timeframe
    Weeks 116, 128, 140, 152, 164, 188, 200, 212, 224,236,248 and 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    41
    46
    Units: percentage of participants
    number (not applicable)
        Week 116 (n=41,46)
    7.3
    8.7
        Week 128 (n=40,43)
    20
    11.6
        Week 140 (n=38,40)
    18.4
    5
        Week 152 (n=27,35)
    3.7
    2.9
        Week 164 (n=27,25)
    3.7
    4
        Week 176 (n=24,22)
    4.2
    0
        Week 188 (n=21,22)
    4.8
    0
        Week 200 (n=19,21)
    5.3
    4.8
        Week 212 (n=18,18)
    5.6
    5.6
        Week 224 (n=17,18)
    5.9
    5.6
        Week 236 (n=16,17)
    12.5
    5.9
        Week 248 (n=15,17)
    0
    5.9
        Week 260 (n=15,15)
    0
    0
    No statistical analyses for this end point

    Secondary: Part III: Percentage of Participants in Clinical Remission off all Arthritis Medications except TCZ for 6 months Prior to Specified Weeks

    Close Top of page
    End point title
    Part III: Percentage of Participants in Clinical Remission off all Arthritis Medications except TCZ for 6 months Prior to Specified Weeks
    End point description
    There were 4 levels of clinical remission defined while the patient remained on tocilizumab as defined below.. After level 1, each successive level required that all the previous level criteria be met: Level 1: inactive disease criteria have been met at all assessments in the last 6 months (180 days) preceding the timepoint assessment day Level 2: level 1 criteria and no oral corticosteroids received in the last 6 months (180 days) preceding the timepoint assessment day Level 3: level 2 criteria and no methotrexate received in the last 6 months (180 days) preceding the timepoint assessment day Level 4: level 3 criteria and no NSAIDs received for sJIA in the last 6 months (180 days) preceding the timepoint assessment day. ITT3 population; n=number of participants contributing to the specific statistic.
    End point type
    Secondary
    End point timeframe
    Weeks 116, 128, 140, 152, 164, 176, 188, 200, 212, 224, 236, 248, and 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    41
    46
    Units: percentage of participants
    number (not applicable)
        Week 116 (n=41,46)
    4.9
    8.7
        Week 128 (n=40,43)
    15
    9.3
        Week 140 (n=38,40)
    15.8
    5
        Week 152 (n=27,35)
    0
    2.9
        Week 164 (n=27,25)
    0
    0
        Week 176 (n=24,22)
    4.2
    0
        Week 188 (n=21,22)
    4.8
    0
        Week 200 (n=19,21)
    5.3
    0
        Week 212 (n=18,18)
    5.6
    0
        Week 224 (n=17,18)
    5.9
    0
        Week 236 (n=16,17)
    12.5
    0
        Week 248 (n=15,17)
    0
    0
        Week 260 (n=15,15)
    0
    0
    No statistical analyses for this end point

    Secondary: Part III: Percentage of Participants Who Develop Anti-TCZ Antibodies

    Close Top of page
    End point title
    Part III: Percentage of Participants Who Develop Anti-TCZ Antibodies
    End point description
    Human antibodies against human antibodies (HAHA), anti-tocilizumab antibodies were assessed by immunogenicity techniques from blood samples drawn every two weeks during Part III of the study. ITT3 population; n=number of participants contributing to the specific statistic.
    End point type
    Secondary
    End point timeframe
    Every 2 weeks from Week 104 to 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    45
    47
    Units: percentage of participants
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Secondary: Part III: Percentage of Participants who Develop Anti-TCZ Antibodies Associated With Drug Hypersensitivity Reactions

    Close Top of page
    End point title
    Part III: Percentage of Participants who Develop Anti-TCZ Antibodies Associated With Drug Hypersensitivity Reactions
    End point description
    HAHA, anti-tocilizumab antibodies were assessed by immunogenicity techniques from blood samples drawn every two weeks during Part III of the study. ITT3 population; n=number of participants contributing to the specific statistic.
    End point type
    Secondary
    End point timeframe
    Every 2 weeks from Week 104 to 260
    End point values
    Participants ≥30 kg Participants <30 kg
    Number of subjects analysed
    45
    47
    Units: percentage of participants
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    AE onset between time of very first drug intake and date of last contact or 30 days after very last drug intake. 30 days after 12 weeks of treatment in Part I, 30 days after up to Week 104 in Part II and 30 days after up to Week 260 in Part III .
    Adverse event reporting additional description
    Adverse Events (AEs) reported in the All Tocilizumab (Part I, Part II and Part III) arm are cumulative to Week 260 and include AEs previously reported in the Tocilizumab_8 mg/kg (Part I) and Tocilizumab_12 mg/kg (Part I) arms that occurred in the 12 week treatment period.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    All Tocilizumab (Part I, II and III)
    Reporting group description
    -

    Serious adverse events
    All Tocilizumab (Part I, II and III)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    48 / 112 (42.86%)
         number of deaths (all causes)
    4
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Drug intolerance
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Influenza like illness
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Abnormal behaviour
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Self injurious behaviour
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Testicular torsion
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Joint dislocation
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Forearm fracture
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fracture
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Liver function test abnormal
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Histiocytosis haematophagic
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences causally related to treatment / all
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pulmonary veno-occlusive disease
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Panniculitis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Urticaria
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Arthritis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Juvenile idiopathic arthritis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Hyperkalaemia
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences causally related to treatment / all
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Varicella
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    Herpes zoster
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 112 (1.79%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    1 / 1
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 112 (1.79%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Kidney infection
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    All Tocilizumab (Part I, II and III)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    112 / 112 (100.00%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    7 / 112 (6.25%)
         occurrences all number
    11
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    11 / 112 (9.82%)
         occurrences all number
    19
    Influenza like illness
         subjects affected / exposed
    10 / 112 (8.93%)
         occurrences all number
    14
    Fatigue
         subjects affected / exposed
    6 / 112 (5.36%)
         occurrences all number
    6
    Local swelling
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    6
    Pain
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    4
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences all number
    13
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    17 / 112 (15.18%)
         occurrences all number
    24
    Ligament sprain
         subjects affected / exposed
    13 / 112 (11.61%)
         occurrences all number
    16
    Contusion
         subjects affected / exposed
    10 / 112 (8.93%)
         occurrences all number
    18
    Excoriation
         subjects affected / exposed
    8 / 112 (7.14%)
         occurrences all number
    8
    Limb injury
         subjects affected / exposed
    8 / 112 (7.14%)
         occurrences all number
    15
    Fall
         subjects affected / exposed
    7 / 112 (6.25%)
         occurrences all number
    7
    Joint injury
         subjects affected / exposed
    7 / 112 (6.25%)
         occurrences all number
    8
    Traumatic haematoma
         subjects affected / exposed
    7 / 112 (6.25%)
         occurrences all number
    10
    Wound
         subjects affected / exposed
    6 / 112 (5.36%)
         occurrences all number
    8
    Hand fracture
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    5
    Laceration
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    5
    Infusion related reaction
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    5
    Muscle strain
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    4
    Thermal burn
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    4
    Investigations
    Transaminases increased
         subjects affected / exposed
    11 / 112 (9.82%)
         occurrences all number
    12
    Neutrophil count decreased
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    13
    Platelet count decreased
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    36
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    5
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    45 / 112 (40.18%)
         occurrences all number
    70
    Oropharyngeal pain
         subjects affected / exposed
    24 / 112 (21.43%)
         occurrences all number
    40
    Nasal congestion
         subjects affected / exposed
    10 / 112 (8.93%)
         occurrences all number
    16
    Epistaxis
         subjects affected / exposed
    9 / 112 (8.04%)
         occurrences all number
    10
    Rhinorrhoea
         subjects affected / exposed
    7 / 112 (6.25%)
         occurrences all number
    8
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    25 / 112 (22.32%)
         occurrences all number
    143
    Leukopenia
         subjects affected / exposed
    11 / 112 (9.82%)
         occurrences all number
    34
    Lymphadenopathy
         subjects affected / exposed
    6 / 112 (5.36%)
         occurrences all number
    12
    Lymphadenitis
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    25 / 112 (22.32%)
         occurrences all number
    53
    Dizziness
         subjects affected / exposed
    6 / 112 (5.36%)
         occurrences all number
    11
    Migraine
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences all number
    6
    Eye disorders
    Cataract
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    4
    Chalazion
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences all number
    6
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    11 / 112 (9.82%)
         occurrences all number
    14
    Middle ear effusion
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    4
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    29 / 112 (25.89%)
         occurrences all number
    44
    Vomiting
         subjects affected / exposed
    29 / 112 (25.89%)
         occurrences all number
    34
    Nausea
         subjects affected / exposed
    26 / 112 (23.21%)
         occurrences all number
    37
    Abdominal pain
         subjects affected / exposed
    16 / 112 (14.29%)
         occurrences all number
    22
    Abdominal pain upper
         subjects affected / exposed
    15 / 112 (13.39%)
         occurrences all number
    21
    Dental caries
         subjects affected / exposed
    6 / 112 (5.36%)
         occurrences all number
    6
    Gastrointestinal disorder
         subjects affected / exposed
    6 / 112 (5.36%)
         occurrences all number
    7
    Abdominal discomfort
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences all number
    4
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    5
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    22 / 112 (19.64%)
         occurrences all number
    31
    Eczema
         subjects affected / exposed
    10 / 112 (8.93%)
         occurrences all number
    18
    Prurigo
         subjects affected / exposed
    8 / 112 (7.14%)
         occurrences all number
    10
    Urticaria
         subjects affected / exposed
    8 / 112 (7.14%)
         occurrences all number
    14
    Dry skin
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    6
    Pruritus
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    9
    Dermatitis atopic
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences all number
    3
    Dermatitis contact
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences all number
    5
    Erythema
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences all number
    4
    Musculoskeletal and connective tissue disorders
    Juvenile idiopathic arthritis
         subjects affected / exposed
    31 / 112 (27.68%)
         occurrences all number
    72
    Arthralgia
         subjects affected / exposed
    25 / 112 (22.32%)
         occurrences all number
    48
    Back pain
         subjects affected / exposed
    12 / 112 (10.71%)
         occurrences all number
    19
    Pain in extremity
         subjects affected / exposed
    12 / 112 (10.71%)
         occurrences all number
    24
    Musculoskeletal pain
         subjects affected / exposed
    11 / 112 (9.82%)
         occurrences all number
    23
    Neck pain
         subjects affected / exposed
    9 / 112 (8.04%)
         occurrences all number
    16
    Joint swelling
         subjects affected / exposed
    7 / 112 (6.25%)
         occurrences all number
    10
    Arthritis
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    9
    Musculoskeletal stiffness
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    6
    Osteoporosis
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences all number
    3
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    53 / 112 (47.32%)
         occurrences all number
    168
    Upper respiratory tract infection
         subjects affected / exposed
    49 / 112 (43.75%)
         occurrences all number
    156
    Gastroenteritis
         subjects affected / exposed
    28 / 112 (25.00%)
         occurrences all number
    43
    Pharyngitis
         subjects affected / exposed
    20 / 112 (17.86%)
         occurrences all number
    26
    Rhinitis
         subjects affected / exposed
    19 / 112 (16.96%)
         occurrences all number
    40
    Ear infection
         subjects affected / exposed
    18 / 112 (16.07%)
         occurrences all number
    34
    Viral infection
         subjects affected / exposed
    16 / 112 (14.29%)
         occurrences all number
    17
    Impetigo
         subjects affected / exposed
    14 / 112 (12.50%)
         occurrences all number
    22
    Otitis media
         subjects affected / exposed
    14 / 112 (12.50%)
         occurrences all number
    15
    Conjunctivitis
         subjects affected / exposed
    12 / 112 (10.71%)
         occurrences all number
    14
    Viral upper respiratory tract infection
         subjects affected / exposed
    12 / 112 (10.71%)
         occurrences all number
    14
    Bronchitis
         subjects affected / exposed
    11 / 112 (9.82%)
         occurrences all number
    15
    Sinusitis
         subjects affected / exposed
    10 / 112 (8.93%)
         occurrences all number
    11
    Urinary tract infection
         subjects affected / exposed
    10 / 112 (8.93%)
         occurrences all number
    30
    Gastroenteritis viral
         subjects affected / exposed
    9 / 112 (8.04%)
         occurrences all number
    9
    Influenza
         subjects affected / exposed
    9 / 112 (8.04%)
         occurrences all number
    12
    Tonsillitis
         subjects affected / exposed
    9 / 112 (8.04%)
         occurrences all number
    11
    Otitis externa
         subjects affected / exposed
    8 / 112 (7.14%)
         occurrences all number
    15
    Paronychia
         subjects affected / exposed
    7 / 112 (6.25%)
         occurrences all number
    10
    Herpes zoster
         subjects affected / exposed
    6 / 112 (5.36%)
         occurrences all number
    6
    Laryngitis
         subjects affected / exposed
    6 / 112 (5.36%)
         occurrences all number
    9
    Cellulitis
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    5
    Skin infection
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    5
    Tinea pedis
         subjects affected / exposed
    5 / 112 (4.46%)
         occurrences all number
    8
    Varicella
         subjects affected / exposed
    4 / 112 (3.57%)
         occurrences all number
    4
    Otitis media acute
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences all number
    4
    Pneumonia
         subjects affected / exposed
    3 / 112 (2.68%)
         occurrences all number
    3

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Jun 2009
    Updated disease definitions including sJIA disease and MAS; Clarified section 4.1.1.2 title to indicate that first open label treatment dose was administered at Week 12 for Part II; Clarified the inclusion and exclusion criteria; Updated treatments allowed and prohibited for sJIA; Updated the withdrawal requirements for patients and discontinuation criteria if patients did not achieve a JIA ACR30 response; Extended the length of the study design from a two-part, 3 year study to a three-part, 5 year study; Clarified the visits and weeks of Part I – the double-blind portion of the study to evaluate efficacy and safety; Changed the day of the Baseline score taken as the pre-dose assessment at Visit 1 (the day of the first infusion of study drug) to Day 1 from Day 0; Updated the timing of reporting to Roche with local serum ferritin results ≥ 3,000 nanograms/milliliter (ng/mL); Clarified the definition of improvement in JIA and Tanner Stage; If at least two consecutive TCZ infusions were missed for safety reasons, quantitative immunoglobulin (Ig) and PK/PD assessments (IL-6, TCZ, sIL-6R and anti-TCZ antibodies) were performed pre-dose at the next scheduled visit and pre-dose 2 weeks later; Clarified responsibility of collaborative groups and the guidance for steroid tapering during and after escape therapy; Added the escape option to allow children with more severe disease at Baseline an opportunity to escape and receive active open-label study drug; To allow varicella zoster immunoglobulin upon exposure to chicken pox in children who had not had chicken pox; Clarified safety parameters and thus improved safety monitoring and reporting.
    07 Jan 2011
    The primary goal of this amendment was to introduce an optional, less frequent, dosing schedule in Part III for patients who had achieved inactive disease while off oral CSs and met specific response criteria. Other changes were made to correct ambiguous or incorrect wording and to improve clarity and included the following: Updated secondary and exploratory endpoints for Part II of the study; Updated the sample size of the study; Changes to add clarity to safety parameters, address safety issues seen with TCZ, and modified risk mitigation rules, particularly related to an infusion related reaction; Protocol additions based on the information which was gathered from the current conduct of the protocol. Clarification of the timing of the interim analyses of efficacy and safety data: at study week 12, when the 50th patient completed the 1 year on TCZ in study Part II, at week 104 (end of study Part II), and at week 260 (end of study Part III).

    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA