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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:
    An open-label extension study of canakinumab (ACZ885) in patients with Systemic Juvenile Idiopathic Arthritis (SJIA) and active systemic manifestations who participated in studies ACZ885G2301 and ACZ885G2305;and response characterization study in canakinumab treatment-naïve patients with active SJIA with and without fever

    Summary
    EudraCT number
    		 2008-008008-42
    Trial protocol
    		 NO   FR   ES   HU   BE   DE   NL   SE   IT   GB   DK   GR   AT   Outside EU/EEA  
    Global end of trial date
    10 Dec 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jul 2016
    First version publication date
    28 Jul 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CACZ885G2301E1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00891046
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000060-PIP02-08
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    10 Dec 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Dec 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the study was to evaluate long-term safety, tolerability and immunogenicity of canakinumab treated subjects with inactive Systemic Juvenile Idiopathic Arthritis (SJIA), rolled over from CACZ885G2301 (EudraCT number: 2008-005479-82) and CACZ885G2305 (EudraCT number: 2008-005476-27) and canakinumab naive subjects with active SJIA.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Sep 2009
    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
    Canada: 14
    Country: Number of subjects enrolled
    Israel: 25
    Country: Number of subjects enrolled
    Netherlands: 11
    Country: Number of subjects enrolled
    Poland: 6
    Country: Number of subjects enrolled
    Spain: 16
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    United Kingdom: 13
    Country: Number of subjects enrolled
    Austria: 3
    Country: Number of subjects enrolled
    Belgium: 16
    Country: Number of subjects enrolled
    France: 41
    Country: Number of subjects enrolled
    Germany: 32
    Country: Number of subjects enrolled
    Greece: 8
    Country: Number of subjects enrolled
    Hungary: 16
    Country: Number of subjects enrolled
    Italy: 9
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    Turkey: 8
    Country: Number of subjects enrolled
    Peru: 3
    Country: Number of subjects enrolled
    Brazil: 9
    Country: Number of subjects enrolled
    United States: 15
    Country: Number of subjects enrolled
    Switzerland: 3
    Country: Number of subjects enrolled
    Russian Federation: 16
    Worldwide total number of subjects
    270
    EEA total number of subjects
    174
    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)
    188
    Adolescents (12-17 years)
    70
    Adults (18-64 years)
    12
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 71 centres in 20 countries.

    Pre-assignment
    Screening details
    		 A total of 147 subjects from studies CACZ885G2301 (EudraCT number: 2008-005479-82) and CACZ885G2305 (EudraCT number: 2008-005476-27) and 123 canakinumab treatment-naive subjects were enrolled into this extension study.

    Period 1
    Period 1 title
    Overall (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    The study was open-label, and hence blinding was not applicable.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ACZ885 treated: Group 1 (Discontinued from core study)
    Arm description
    		 Subjects who discontinued from CACZ885G2301 study due to flares, non response or any other reason - Part II (EudraCT number: 2008-005479-82), received a subcutaneous (s.c.) injection of canakinumab 4 mg/kg every 4 weeks unless discontinuation occurs.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Canakinumab
    Investigational medicinal product code
    ACZ885
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Canakinumab (2 mg/kg or 4 mg/kg) s.c. injection was administered every 4 weeks.

    Arm title
    		 ACZ885 treated: Group 2 (Completed core study)
    Arm description
    		 Subjects who completed study CACZ885G2301 - Part II (EudraCT number: 2008-005479-82), received an s.c. injection of canakinumab 4 mg/kg every 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Canakinumab
    Investigational medicinal product code
    ACZ885
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Canakinumab (2 mg/kg or 4 mg/kg) s.c. injection was administered every 4 weeks.

    Arm title
    		 ACZ885 treated: Group 3 (Steroid taper failures in core study)
    Arm description
    		 Subjects who failed to taper their steroid dose in CACZ885G2301 Study - Part I (EudraCT number: 2008-005479-82); received an s.c. injection of canakinumab 4 mg/kg every 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Canakinumab
    Investigational medicinal product code
    ACZ885
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Canakinumab (2 mg/kg or 4 mg/kg) s.c. injection was administered every 4 weeks.

    Arm title
    		 ACZ885 treated: Group 4 (Other criteria)
    Arm description
    		 Subjects who previously received canakinumab treatment in Studies CACZ885G2301 (EudraCT number: 2008-005479-82) and CACZ885G2305 (EudraCT number: 2008-005476-27), but did not fulfill the criteria for Group 1, 2 or 3, received a s.c. injection of canakinumab 4 mg/kg every 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Canakinumab
    Investigational medicinal product code
    ACZ885
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Canakinumab (2 mg/kg or 4 mg/kg) s.c. injection was administered every 4 weeks.

    Arm title
    		 ACZ885 treatment naive
    Arm description
    		 Subjects who were canakinumab treatment-naïve and did not participate in previous canakinumab studies, received a s.c. injection of canakinumab 4 mg/kg every 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Canakinumab
    Investigational medicinal product code
    ACZ885
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Canakinumab (2 mg/kg or 4 mg/kg) s.c. injection was administered every 4 weeks.

    Number of subjects in period 1
    		ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria) ACZ885 treatment naive
    Started
    33
    63
    40
    11
    123
    Completed
    21
    54
    17
    8
    84
    Not completed
    12
    9
    23
    3
    39
         Consent withdrawn by subject
    2
    1
    2
    1
    1
         Adverse event, non-fatal
    4
    3
    2
    -
    14
         Unsatisfactory therapeutic effect
    5
    -
    19
    2
    20
         Subject's condition no longer required study drug
    -
    2
    -
    -
    1
         Administrative problems
    -
    -
    -
    -
    1
         Unsatisfatory therapeutic effect
    -
    2
    -
    -
    -
         Lost to follow-up
    -
    -
    -
    -
    1
         Protocol deviation
    1
    1
    -
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    ACZ885 treated: Group 1 (Discontinued from core study)
    Reporting group description
    		 Subjects who discontinued from CACZ885G2301 study due to flares, non response or any other reason - Part II (EudraCT number: 2008-005479-82), received a subcutaneous (s.c.) injection of canakinumab 4 mg/kg every 4 weeks unless discontinuation occurs.

    Reporting group title
    ACZ885 treated: Group 2 (Completed core study)
    Reporting group description
    		 Subjects who completed study CACZ885G2301 - Part II (EudraCT number: 2008-005479-82), received an s.c. injection of canakinumab 4 mg/kg every 4 weeks.

    Reporting group title
    ACZ885 treated: Group 3 (Steroid taper failures in core study)
    Reporting group description
    		 Subjects who failed to taper their steroid dose in CACZ885G2301 Study - Part I (EudraCT number: 2008-005479-82); received an s.c. injection of canakinumab 4 mg/kg every 4 weeks.

    Reporting group title
    ACZ885 treated: Group 4 (Other criteria)
    Reporting group description
    		 Subjects who previously received canakinumab treatment in Studies CACZ885G2301 (EudraCT number: 2008-005479-82) and CACZ885G2305 (EudraCT number: 2008-005476-27), but did not fulfill the criteria for Group 1, 2 or 3, received a s.c. injection of canakinumab 4 mg/kg every 4 weeks.

    Reporting group title
    ACZ885 treatment naive
    Reporting group description
    		 Subjects who were canakinumab treatment-naïve and did not participate in previous canakinumab studies, received a s.c. injection of canakinumab 4 mg/kg every 4 weeks.

    Reporting group values
    		 ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria) ACZ885 treatment naive Total
    Number of subjects
    		 33 63 40 11 123 270
    Age categorical
    Units: Subjects
        2 - <4 years
    		 0 2 3 1 18 24
        4 - <6 years
    		 6 10 6 5 15 42
        6 - <12 years
    		 16 32 21 3 50 122
        12 - <20 years
    		 11 17 10 2 40 80
        ≥ 20 years
    		 0 2 0 0 0 2
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 9.8 ± 4.25 9.9 ± 4.66 9.1 ± 4.35 7.8 ± 4.77 9 ± 4.52 -
    Gender categorical
    Units: Subjects
        Female
    		 19 34 23 5 75 156
        Male
    		 14 29 17 6 48 114

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    ACZ885 treated: Group 1 (Discontinued from core study)
    Reporting group description
    		 Subjects who discontinued from CACZ885G2301 study due to flares, non response or any other reason - Part II (EudraCT number: 2008-005479-82), received a subcutaneous (s.c.) injection of canakinumab 4 mg/kg every 4 weeks unless discontinuation occurs.

    Reporting group title
    ACZ885 treated: Group 2 (Completed core study)
    Reporting group description
    		 Subjects who completed study CACZ885G2301 - Part II (EudraCT number: 2008-005479-82), received an s.c. injection of canakinumab 4 mg/kg every 4 weeks.

    Reporting group title
    ACZ885 treated: Group 3 (Steroid taper failures in core study)
    Reporting group description
    		 Subjects who failed to taper their steroid dose in CACZ885G2301 Study - Part I (EudraCT number: 2008-005479-82); received an s.c. injection of canakinumab 4 mg/kg every 4 weeks.

    Reporting group title
    ACZ885 treated: Group 4 (Other criteria)
    Reporting group description
    		 Subjects who previously received canakinumab treatment in Studies CACZ885G2301 (EudraCT number: 2008-005479-82) and CACZ885G2305 (EudraCT number: 2008-005476-27), but did not fulfill the criteria for Group 1, 2 or 3, received a s.c. injection of canakinumab 4 mg/kg every 4 weeks.

    Reporting group title
    ACZ885 treatment naive
    Reporting group description
    		 Subjects who were canakinumab treatment-naïve and did not participate in previous canakinumab studies, received a s.c. injection of canakinumab 4 mg/kg every 4 weeks.

    Subject analysis set title
    ACZ885 treated
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects who were responsive to canakinumab in previous studies: CACZ885G2301 (EudraCT number: 2008-005479-82) and CACZ885G2305 (EudraCT number: 2008-005476-27) and entered into this extension study in Group 1, 2, 3 and 4.

    Subject analysis set title
    Male subjects aged 6-20 years
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Male subjects (age lying in following categories: 6-9 years, 9-11 years and 11-20 years) who received a s.c. injection of canakinumab 4 mg/kg every 4 weeks during the study.

    Subject analysis set title
    Female subjects aged 6-20 years
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Female subjects (age lying in following categories: 6-9 years, 9-11 years and 11-20 years) who received a s.c. injection of canakinumab 4 mg/kg every 4 weeks during the study.

    Primary: Number of subjects with adverse events (AEs), treatment related AEs, AEs leading to discontinuation, AEs by severity, serious adverse events (SAEs), SAEs leading to discontinuation

    		 Close Top of page
    End point title
    		 Number of subjects with adverse events (AEs), treatment related AEs, AEs leading to discontinuation, AEs by severity, serious adverse events (SAEs), SAEs leading to discontinuation [1] [2]
    End point description
    An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. Treatment related AEs or SAEs were defined as AEs or SAEs that were suspected to be related to study treatment as per investigator. The analysis was performed in safety set, defined as all subjects who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    From start of study treatment (Day 1) to end of follow-up period (Week 271)
    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: Only descriptive summary statistics was planned for this primary outcome measure.
    [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: The end point is reporting pooled data for Group 1, 2, 3 and 4 in 'ACZ treated' arm.
    End point values
    		 ACZ885 treatment naive ACZ885 treated
    Number of subjects analysed
    123
    147
    Units: Subjects
    number (not applicable)
        AEs
    108
    137
        SAEs
    40
    47
        Discontinuation due to any AE
    14
    18
        Discontinuation due to any SAE
    13
    14
        Treatment Related AEs
    44
    57
        Treatment related SAEs
    1
    4
    No statistical analyses for this end point

    Primary: Number of subjects with anti­ACZ885 antibodies at any visit during the study

    		 Close Top of page
    End point title
    		 Number of subjects with anti­ACZ885 antibodies at any visit during the study [3] [4]
    End point description
    Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system. The analysis was performed on the FAS population.
    End point type
    Primary
    End point timeframe
    From start of study treatment (Day 1) to end of follow­-up period (Week 271)
    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: Only descriptive summary statistics was planned for this primary outcome measure.
    [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: The end point is reporting pooled data for Group 1, 2, 3 and 4 in 'ACZ treated' arm.
    End point values
    		 ACZ885 treatment naive ACZ885 treated
    Number of subjects analysed
    123
    147
    Units: subjects
    0
    0
    No statistical analyses for this end point

    Primary: Number of subjects with clinically significant local injection site reactions during the study

    		 Close Top of page
    End point title
    		 Number of subjects with clinically significant local injection site reactions during the study [5] [6]
    End point description
    Local injection site tolerability was assessed on the injection site. Each subject was classified into one of the following four categories: 1. no tolerability reactions at any time during the study, 2. mild reaction observed on at least one occasion but no moderate or severe reactions. 3. moderate reaction observed on at least one occasion but no severe reaction. 4. severe reaction observed on at least one occasion. The analysis was performed in SS population.
    End point type
    Primary
    End point timeframe
    From start of study treatment (Day 1) to end of follow-­up period (Week 271)
    Notes
    [5] - 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: The end point is reporting pooled data for Group 1, 2, 3 and 4 in 'ACZ treated' arm.
    [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: Only descriptive summary statistics was planned for this primary outcome measure.
    End point values
    		 ACZ885 treatment naive ACZ885 treated
    Number of subjects analysed
    123
    147
    Units: subjects
        No tolerability reaction
    115
    129
        Mild tolerability reaction
    6
    15
        Moderate tolerability reaction
    2
    3
        Severe tolerability reaction
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of non-responders at end of prior study who achieved minimum response of American College of Rheumatology (ACR) pediatric 30/50/70/90/100 criteria at end of the present study

    		 Close Top of page
    End point title
    		 Percentage of non-responders at end of prior study who achieved minimum response of American College of Rheumatology (ACR) pediatric 30/50/70/90/100 criteria at end of the present study [7]
    End point description
    Adapted ACR Paediatric 30/50/70/90 or 100 criteria was assessed based on following 7 variables: 1.Physician’s Global Assessment on a 0-100 millimetres (mm) visual analog scale (VAS); 2. Patient Global Assessment on a 0­-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of C-reactive protein (CRP) and 7.Absence of intermittent fever due to severe juvenile idiopathic arthritis (SJIA) during the preceding week. Response was defined as more than or equal to (≥) 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperatureless than or equal to (≤) 38 degree celsius [°C]) in the preceding week (variable 7) and with no more than one variable 1 to ­6, worsening by more than 30%. The analysis was done in FAS population. Here 'Number of subjects analysed' signifies number of subjects with an ACR assessment at the given visit.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment (LSLV) or date of discontinuation, which ever occurred earlier
    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: The ACR pediatric scores was collected for subjects who met the minimum of ACR criteria at baseline in 'ACZ treated' cohort i.e. Group 1, 2, 3 and 4.
    End point values
    		 ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria)
    Number of subjects analysed
    17
    0 [8]
    17
    6
    Units: percentage of subjects
    number (not applicable)
        ACR ≥30 criteria
    82.4
    76.5
    83.3
        ACR ≥ 50 criteria
    82.4
    70.6
    83.3
        ACR ≥ 70 criteria
    82.4
    52.9
    83.3
        ACR ≥ 90 criteria
    76.5
    23.5
    50
        ACR 100 criteria
    58.8
    17.6
    50
    Notes
    [8] - No subject was analyzed in this group.
    No statistical analyses for this end point

    Secondary: Percentage of subjects with minimum adapted ACR pediatric ≥ 30 at baseline who achieved minimum response of ACR pediatric 30/50/70/90/100 criteria at last assessment of study

    		 Close Top of page
    End point title
    		 Percentage of subjects with minimum adapted ACR pediatric ≥ 30 at baseline who achieved minimum response of ACR pediatric 30/50/70/90/100 criteria at last assessment of study [9]
    End point description
    Adapted ACR Paediatric 30/50/70/90 or 100 criteria was assessed based on following 7 variables: 1.Physician’s Global Assessment on a 0-100 mm VAS; 2. Patient Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of CRP and 7.Absence of intermittent fever due to sJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever in the preceding week (variable 7) and with no more than one variable 1 to 6 worsening by more than 30%. For minimum adapted ACR paediatric scores, the last measurement recorded from the subject’s previous study was considered baseline for the current study. The analysis was done in FAS population. Here 'Number of subjects analysed' signifies number of subjects with an ACR assessment at the given visit.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment or date of discontinuation, which ever occurred earlier
    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: The ACR pediatric scores was collected for subjects who met the minimum of ACR 30 criteria at baseline in 'ACZ treated' cohort i.e. Group 1, 2, 3 and 4.
    End point values
    		 ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria)
    Number of subjects analysed
    16
    63
    23
    5
    Units: percentage of subjects
    number (not applicable)
        ACR ≥ 30
    100
    100
    91.3
    100
        ACR ≥ 50
    100
    100
    87
    100
        ACR ≥ 70
    100
    100
    78.3
    100
        ACR ≥ 90
    100
    100
    69.6
    100
        ACR 100
    87.5
    93.7
    39.1
    80
    No statistical analyses for this end point

    Secondary: Percentage of subjects able to taper oral steroid use or reached steroid free regimen

    		 Close Top of page
    End point title
    		 Percentage of subjects able to taper oral steroid use or reached steroid free regimen
    End point description
    Steroid tapering with oral steroids was allowed if the subject achieved an adapted ACR Paediatric 50 response and had no fever. A subject was considered to have tapered steroids successfully, if the steroid dose was reduced from baseline and the subject did not flare and maintained a minimum adapted ACR Paediatric 30 at the last measurement. A subject was considered to have unsuccessfully tapered steroids if the steroid dose was reduced during the study but dose at last assessment was equal to or greater than dose at baseline or; if steroid dose was reduced but the subject did not maintain a minimum adapted ACR Paediatric 30 at the last measurement. The analysis was done in FAS population. Here 'Number of subjects analysed' signifies number of subjects who were steroid users at baseline.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment or date of discontinuation, which ever occurred earlier
    End point values
    		 ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria) ACZ885 treatment naive
    Number of subjects analysed
    33
    63
    40
    11
    123
    Units: percentage of subjects
    number (not applicable)
        Steroid free (n = 11,9,38,8,71)
    36.4
    55.6
    23.7
    25
    33.8
        Successfully tapered (n = 11,9,38,8,71)
    27.3
    0
    21.1
    25
    23.9
        Unsuccessfully tapered (n = 11,9,38,8,71)
    18.2
    22.2
    18.4
    25
    11.3
        Not tapered (n = 11,9,38,8,71)
    18.2
    22.2
    36.8
    25
    31
    No statistical analyses for this end point

    Secondary: Number of subjects who reduced their canakinumab dose to 2 mg/kg

    		 Close Top of page
    End point title
    		 Number of subjects who reduced their canakinumab dose to 2 mg/kg
    End point description
    The canakinumab dose could be reduced from 4 mg/kg to 2 mg/kg in subjects who were steroid-free, if requested by the treating physician and agreed by the sponsor. For treatment naive subjects, dose reduction was allowed after the subject had received 6 months treatment with canakinumab. The analysis was done in FAS population.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment or date of discontinuation, which ever occurred earlier
    End point values
    		 ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria) ACZ885 treatment naive
    Number of subjects analysed
    33
    63
    40
    11
    123
    Units: number of subjects
    9
    29
    4
    2
    18
    No statistical analyses for this end point

    Secondary: Percentage of subjects with inactive disease

    		 Close Top of page
    End point title
    		 Percentage of subjects with inactive disease
    End point description
    Inactive disease was defined as no joints with active arthritis; no fever (body temperature ≤ 38 degree Celsius); no rheumatoid rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to SJIA; normal CRP, and a rating of no disease activity on the Physician’s Global Assessment of disease activity (with a best possible score ≤10 mm on the VAS). The analysis was performed in FAS population. Here 'Number of subjects analysed' signifies number of subjects with an assessment in the given visit.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment (LSLV: 10-Dec-2014) or date of discontinuation, which ever occurred earlier
    End point values
    		 ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria) ACZ885 treatment naive
    Number of subjects analysed
    33
    63
    40
    11
    122
    Units: Percentage of subjects
        number (not applicable)
    39.4
    79.4
    12.5
    36.4
    50.8
    No statistical analyses for this end point

    Secondary: Percentage of subjects with clinical remission

    		 Close Top of page
    End point title
    		 Percentage of subjects with clinical remission [10]
    End point description
    Clinical remission was defined as at least 6 months of inactive disease or at least 12 months of inactive disease on medication during the extension period. Subjects with inactive disease for at least 6 months, but had loss of inactive disease before 12 months were also determined. The analysis was done in FAS population. Here 'Number of subjects analysed' signifies number of subjects with an assessment in the given visit.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment (LSLV: 10-Dec-2014) or date of discontinuation, which ever occurred earlier
    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: The end point is reporting pooled data for Group 1, 2, 3 and 4 in 'ACZ treated' arm.
    End point values
    		 ACZ885 treatment naive ACZ885 treated
    Number of subjects analysed
    123
    147
    Units: percentage of subjects
    number (not applicable)
        At least 6 consecutive months of inactive disease
    42.3
    52.4
        At least 12 consecutive months of inactive disease
    26.8
    42.9
        Loss of inactive disease after 6 months
    8.9
    6.8
    No statistical analyses for this end point

    Secondary: Change from baseline in disability, overall well-being and pain intensity scores based on Child Health Assessment Questionnaire (CHAQ) to last assessment of study

    		 Close Top of page
    End point title
    		 Change from baseline in disability, overall well-being and pain intensity scores based on Child Health Assessment Questionnaire (CHAQ) to last assessment of study
    End point description
    The CHAQ was used to assess physical ability, overall well-being and pain intensity experienced by subjects. The CHAQ disability dimension consisted of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and other “activities”. Parents graded the response in four categories, ranging from 0 (without any difficulty) to 3 (unable to do). Subject's pain intensity was assessed by parents and adult subjects (18-20 years old) on a VAS scale of 0-100 mm (0 mm: no pain to 100: very severe pain). Change from baseline was calculated by using the formula = (post baseline value – baseline value). A negative change from baseline indicates improvement. The analysis was performed in FAS population.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment (LSLV: 10-Dec-2014) or date of discontinuation, which ever occurred earlier
    End point values
    		 ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria) ACZ885 treatment naive
    Number of subjects analysed
    33
    63
    40
    11
    121
    Units: Units on a scale
    median (full range (min-max))
        Disability score
    -0.375 (-2 to 0.625)
    0 (-1.5 to 2.125)
    -0.125 (-1.25 to 2.25)
    0 (-2.125 to 1.375)
    -0.7143 (-3 to 2.5)
        Overall well-being score
    -18 (-64 to 54)
    0 (-36 to 81)
    0 (-36 to 1)
    -10 (-69 to 20)
    -28 (-100 to 83)
        Pain Intensity score
    -13 (-69 to 39)
    0 (-39 to 80)
    0 (-58 to 93)
    0 (-57 to 53)
    -39 (-100 to 89)
    No statistical analyses for this end point

    Secondary: Change from baseline in Health-Related Quality of Life (HRQoL) over time based on Child Health Questionnaire - Parent Form (CHQ-PF50) to last assessment of study

    		 Close Top of page
    End point title
    		 Change from baseline in Health-Related Quality of Life (HRQoL) over time based on Child Health Questionnaire - Parent Form (CHQ-PF50) to last assessment of study
    End point description
    The Child Health Questionnaire – Parent Form (CHQ-PF50) instrument was used to measure HRQoL aged 5 to 18 years from a parent’s perspective. This 14­concept questionnaire measured physical and psychosocial health of the subjects on following points: physical functioning, role/social emotional, role/social behavior, role/social physical, bodily pain, general behavior, mental health, self esteem, general health perception, change in health, parental impact - emotional, parental impact – time, family activities, and family cohesion. Total score ranged from 0-100. Increase in score represented improvement in overall well­being of subjects. Change from baseline was calculated by using the formula = (post­baseline value – baseline value). The analysis was performed in FAS population.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment (LSLV: 10-Dec-2014) or date of discontinuation, which ever occurred earlier
    End point values
    		 ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria) ACZ885 treatment naive
    Number of subjects analysed
    26
    44
    29
    8
    90
    Units: Units on a scale
    median (full range (min-max))
        CHQ-PF50 physical score
    14.0407 (-18.289 to 38.33)
    0.6959 (-14.663 to 23.833)
    1.3716 (-42.009 to 41.275)
    13.9255 (-3.074 to 37.083)
    18.8758 (-38.587 to 60.661)
        CHQ-PF50 psychosocial score
    3.8815 (-22.516 to 22.471)
    1.4004 (-14.99 to 30.982)
    0.7582 (-21.674 to 22.907)
    11.9798 (-5.931 to 33.497)
    9.3209 (-23.862 to 48.657)
    No statistical analyses for this end point

    Secondary: Change from baseline in EuroQual 5-Dimension health status questionnaire (EQ-5D) utility index and health state assessment scores to last assessment of study

    		 Close Top of page
    End point title
    		 Change from baseline in EuroQual 5-Dimension health status questionnaire (EQ-5D) utility index and health state assessment scores to last assessment of study
    End point description
    EQ-5D HRQoL tool was employed for subjects above 12 years of age and EQ-5D proxy was employed for subjects 8 – 11 years of age). EQ-5D was not completed for subjects aged 7 years and younger. The utility based EQ-5D questionnaire was in two parts and provides a generic measure of health for clinical and economic appraisal. The health state classification part contains 5 questions each with 3 categories (no problem, moderate problem, severe problems). The visual analogue scale was measured from 0 (worst imaginable health state) to 100 (best imaginable health state). A positive change from baseline score indicated improvement. The analysis was performed in FAS population.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment (LSLV: 10-Dec-2014) or date of discontinuation, which ever occurred earlier
    End point values
    		 ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria) ACZ885 treatment naive
    Number of subjects analysed
    17
    35
    22
    4
    65
    Units: Units on a scale
    median (full range (min-max))
        Health State Assessment
    21 (-45 to 63)
    0 (-17 to 49)
    5 (-86 to 50)
    28 (0 to 65)
    30 (-24 to 95)
         EQ-­5D Utility Index Score
    0.204 (-0.636 to 0.945)
    0 (-0.434 to 0.377)
    0.069 (-1.181 to 0.508)
    0.2385 (0 to 0.741)
    0.228 (-0.434 to 1.291)
    No statistical analyses for this end point

    Secondary: Change from baseline in Pediatric Daytime Sleepiness Scale (PDSS) score to last assessment of study

    		 Close Top of page
    End point title
    		 Change from baseline in Pediatric Daytime Sleepiness Scale (PDSS) score to last assessment of study [11]
    End point description
    Sleep patterns in children and adolescents aged between 11 and 15 years were determined using PDSS instrument. Subjects were assessed for 8 items of PDSS on a scale of 0 to 4 (0 – never, 1 – seldom, 2- sometimes, 3 – frequently and 4 – always). Change from baseline was calculated by using the formula = (post­baseline value – baseline value). A positive change from baseline score indicated improvement in sleep patterns. The analysis was performed in FAS population. Here, ‘Number of subjects analysed’ signifies those subjects with a value at both baseline and the respective post-baseline time point.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment (LSLV: 10-Dec-2014) or date of discontinuation, which ever occurred earlier
    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: The PDSS score was collected for subjects in 'ACZ treated' cohort i.e. Group 1, 2, 3 and 4.
    End point values
    		 ACZ885 treated: Group 1 (Discontinued from core study) ACZ885 treated: Group 2 (Completed core study) ACZ885 treated: Group 3 (Steroid taper failures in core study) ACZ885 treated: Group 4 (Other criteria)
    Number of subjects analysed
    9
    12
    5
    2
    Units: Units on a scale
        median (full range (min-max))
    1 (-9 to 4)
    0.5 (-6 to 9)
    0 (-4 to 6)
    -4.5 (-11 to 2)
    No statistical analyses for this end point

    Secondary: Change from baseline in growth velocity parameters to last assessment of study

    		 Close Top of page
    End point title
    		 Change from baseline in growth velocity parameters to last assessment of study [12]
    End point description
    Growth velocity parameters like height, weight and BMI percentiles were determined. Percentiles were based on the growth charts smoothed percentile curves released by Centers for Disease control and prevention (CDC) in 2000, by sex and age. The analysis was performed in FAS population. Here, ‘Number of subjects analysed’ signifies those subjects with a value at both baseline and the respective post-baseline time point.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment (LSLV: 10-Dec-2014) or date of discontinuation, which ever occurred earlier
    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: The end point is reporting pooled data for Group 1, 2, 3 and 4 in 'ACZ treated' arm.
    End point values
    		 ACZ885 treatment naive ACZ885 treated
    Number of subjects analysed
    123
    147
    Units: As defined in categories
    median (full range (min-max))
        Height (cm) percentile (n=123, 139)
    -0.01 (-66.18 to 47.06)
    0 (-37.94 to 37.12)
        Weight (kg) percentile (n=123, 145)
    0.1 (-47.35 to 82.84)
    0 (-62.49 to 56.87)
        BMI (kg/meters^2) percentile (n=123, 139)
    1.08 (-66.95 to 76.3)
    -0.77 (-72.88 to 88.47)
    No statistical analyses for this end point

    Secondary: Number of subjects with clinically significant changes in Tanner staging score during the study

    		 Close Top of page
    End point title
    		 Number of subjects with clinically significant changes in Tanner staging score during the study
    End point description
    Tanner staging, a well­-established scale ranging from 1 to 5, characterizes physical development and quantifies primary and secondary sex characteristics such as the size of the breasts, genitalia, and development of pubic hair in subjects aged 6-20 years. Clinically significant findings were defined as any results which were observed beyond the expected limits as per the discretion of investigator. The analysis was performed in FAS population.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment (LSLV: 10-Dec-2014) or date of discontinuation, which ever occurred earlier
    End point values
    		 Female subjects aged 6-20 years Male subjects aged 6-20 years
    Number of subjects analysed
    59
    55
    Units: Subjects
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of ACZ naive subjects at baseline who achieved minimum response of ACR pediatric 30/50/70/90/100 criteria at last assessment of study

    		 Close Top of page
    End point title
    		 Percentage of ACZ naive subjects at baseline who achieved minimum response of ACR pediatric 30/50/70/90/100 criteria at last assessment of study [13]
    End point description
    Adapted ACR Paediatric 30/50/70/90 or 100 criteria was assessed based on following 7 variables: 1.Physician’s Global Assessment on a 0-100 mm VAS; 2. Patient Global Assessment on a 0--100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of CRP and 7.Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature ≤ 38°C) in the preceding week (variable 7) and with no more than one variable 1 to -6, worsening by more than 30%. The analysis was done in FAS population. Here 'Number of subjects analysed' signifies number of subjects with an ACR assessment at the given visit.
    End point type
    Secondary
    End point timeframe
    Baseline up to last assessment or date of discontinuation, which ever occurred earlier
    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: The end point is reporting only ACZ naive data.
    End point values
    		 ACZ885 treatment naive
    Number of subjects analysed
    121
    Units: Percentage of subjects
    number (not applicable)
        ACR ≥30 criteria
    92.6
        ACR ≥50 criteria
    90.9
        ACR ≥70 criteria
    87.6
        ACR ≥90 criteria
    78.5
        ACR ≥100 criteria
    66.1
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Timeframe for AE
    Adverse event reporting additional description
    AE additional description
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Cohort 1
    Reporting group description
    		 Cohort 1

    Reporting group title
    Cohort 2
    Reporting group description
    		 Cohort 2

    Serious adverse events
    		 Cohort 1 Cohort 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    47 / 147 (31.97%)
    40 / 123 (32.52%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anaplastic large cell lymphoma T- and null-cell types
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Device dislocation
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug ineffective
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury associated with device
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 147 (3.40%)
    4 / 123 (3.25%)
         occurrences causally related to treatment / all
    1 / 5
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vulvovaginal pain
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute interstitial pneumonitis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Abnormal behaviour
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Serum ferritin increased
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula site complication
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transfusion-related acute lung injury
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior sagittal sinus thrombosis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Abdominal lymphadenopathy
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Histiocytosis haematophagic
         subjects affected / exposed
    10 / 147 (6.80%)
    6 / 123 (4.88%)
         occurrences causally related to treatment / all
    8 / 12
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 147 (0.68%)
    2 / 123 (1.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    0 / 147 (0.00%)
    3 / 123 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    1 / 147 (0.68%)
    3 / 123 (2.44%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenomegaly
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 147 (1.36%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Autoimmune hepatitis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    2 / 147 (1.36%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis toxic
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatomegaly
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    1 / 147 (0.68%)
    2 / 123 (1.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug reaction with eosinophilia and systemic symptoms
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eczema
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Henoch-Schonlein purpura
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ingrowing nail
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    2 / 147 (1.36%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic skin eruption
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure acute
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc compression
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Juvenile idiopathic arthritis
         subjects affected / exposed
    14 / 147 (9.52%)
    13 / 123 (10.57%)
         occurrences causally related to treatment / all
    4 / 22
    1 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    2 / 147 (1.36%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal disorder
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyarthritis
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 123 (1.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess neck
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus hepatitis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Furuncle
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    4 / 147 (2.72%)
    2 / 123 (1.63%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis yersinia
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal viral infection
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impetigo
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected bites
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymph node abscess
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphangitis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parvovirus infection
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 147 (1.36%)
    3 / 123 (2.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudocroup
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salmonella sepsis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scarlet fever
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    2 / 147 (1.36%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillitis streptococcal
         subjects affected / exposed
    2 / 147 (1.36%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxoplasmosis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicella
         subjects affected / exposed
    3 / 147 (2.04%)
    1 / 123 (0.81%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 123 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1 Cohort 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    124 / 147 (84.35%)
    91 / 123 (73.98%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    8 / 147 (5.44%)
    5 / 123 (4.07%)
         occurrences all number
    14
    6
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma
         subjects affected / exposed
    14 / 147 (9.52%)
    4 / 123 (3.25%)
         occurrences all number
    16
    4
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    9 / 147 (6.12%)
    12 / 123 (9.76%)
         occurrences all number
    12
    12
    Contusion
         subjects affected / exposed
    11 / 147 (7.48%)
    0 / 123 (0.00%)
         occurrences all number
    14
    0
    Fall
         subjects affected / exposed
    11 / 147 (7.48%)
    7 / 123 (5.69%)
         occurrences all number
    18
    7
    Ligament sprain
         subjects affected / exposed
    11 / 147 (7.48%)
    5 / 123 (4.07%)
         occurrences all number
    21
    7
    Nervous system disorders
    Headache
         subjects affected / exposed
    30 / 147 (20.41%)
    24 / 123 (19.51%)
         occurrences all number
    110
    84
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    10 / 147 (6.80%)
    3 / 123 (2.44%)
         occurrences all number
    16
    7
    Pyrexia
         subjects affected / exposed
    38 / 147 (25.85%)
    27 / 123 (21.95%)
         occurrences all number
    72
    48
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    10 / 147 (6.80%)
    7 / 123 (5.69%)
         occurrences all number
    16
    8
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    21 / 147 (14.29%)
    22 / 123 (17.89%)
         occurrences all number
    35
    56
    Abdominal pain upper
         subjects affected / exposed
    18 / 147 (12.24%)
    13 / 123 (10.57%)
         occurrences all number
    66
    31
    Nausea
         subjects affected / exposed
    17 / 147 (11.56%)
    11 / 123 (8.94%)
         occurrences all number
    30
    27
    Diarrhoea
         subjects affected / exposed
    30 / 147 (20.41%)
    16 / 123 (13.01%)
         occurrences all number
    53
    25
    Vomiting
         subjects affected / exposed
    35 / 147 (23.81%)
    18 / 123 (14.63%)
         occurrences all number
    66
    24
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    37 / 147 (25.17%)
    28 / 123 (22.76%)
         occurrences all number
    102
    49
    Epistaxis
         subjects affected / exposed
    10 / 147 (6.80%)
    5 / 123 (4.07%)
         occurrences all number
    24
    7
    Oropharyngeal pain
         subjects affected / exposed
    36 / 147 (24.49%)
    17 / 123 (13.82%)
         occurrences all number
    98
    30
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    12 / 147 (8.16%)
    16 / 123 (13.01%)
         occurrences all number
    15
    22
    Urticaria
         subjects affected / exposed
    7 / 147 (4.76%)
    7 / 123 (5.69%)
         occurrences all number
    12
    9
    Rash
         subjects affected / exposed
    15 / 147 (10.20%)
    13 / 123 (10.57%)
         occurrences all number
    26
    18
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    36 / 147 (24.49%)
    25 / 123 (20.33%)
         occurrences all number
    79
    56
    Arthritis
         subjects affected / exposed
    9 / 147 (6.12%)
    7 / 123 (5.69%)
         occurrences all number
    11
    10
    Back pain
         subjects affected / exposed
    11 / 147 (7.48%)
    9 / 123 (7.32%)
         occurrences all number
    18
    13
    Joint swelling
         subjects affected / exposed
    9 / 147 (6.12%)
    5 / 123 (4.07%)
         occurrences all number
    21
    10
    Juvenile idiopathic arthritis
         subjects affected / exposed
    23 / 147 (15.65%)
    27 / 123 (21.95%)
         occurrences all number
    46
    65
    Myalgia
         subjects affected / exposed
    9 / 147 (6.12%)
    6 / 123 (4.88%)
         occurrences all number
    15
    6
    Neck pain
         subjects affected / exposed
    8 / 147 (5.44%)
    7 / 123 (5.69%)
         occurrences all number
    18
    7
    Pain in extremity
         subjects affected / exposed
    19 / 147 (12.93%)
    12 / 123 (9.76%)
         occurrences all number
    43
    13
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    13 / 147 (8.84%)
    6 / 123 (4.88%)
         occurrences all number
    15
    6
    Conjunctivitis
         subjects affected / exposed
    8 / 147 (5.44%)
    6 / 123 (4.88%)
         occurrences all number
    9
    7
    Influenza
         subjects affected / exposed
    14 / 147 (9.52%)
    4 / 123 (3.25%)
         occurrences all number
    19
    4
    Gastroenteritis
         subjects affected / exposed
    28 / 147 (19.05%)
    19 / 123 (15.45%)
         occurrences all number
    39
    29
    Nasopharyngitis
         subjects affected / exposed
    47 / 147 (31.97%)
    32 / 123 (26.02%)
         occurrences all number
    121
    56
    Otitis media
         subjects affected / exposed
    11 / 147 (7.48%)
    7 / 123 (5.69%)
         occurrences all number
    12
    7
    Oral herpes
         subjects affected / exposed
    11 / 147 (7.48%)
    1 / 123 (0.81%)
         occurrences all number
    22
    1
    Pharyngitis
         subjects affected / exposed
    15 / 147 (10.20%)
    15 / 123 (12.20%)
         occurrences all number
    22
    18
    Respiratory tract infection
         subjects affected / exposed
    7 / 147 (4.76%)
    13 / 123 (10.57%)
         occurrences all number
    10
    21
    Tonsillitis
         subjects affected / exposed
    10 / 147 (6.80%)
    7 / 123 (5.69%)
         occurrences all number
    14
    9
    Rhinitis
         subjects affected / exposed
    35 / 147 (23.81%)
    26 / 123 (21.14%)
         occurrences all number
    81
    45
    Upper respiratory tract infection
         subjects affected / exposed
    36 / 147 (24.49%)
    24 / 123 (19.51%)
         occurrences all number
    100
    54
    Urinary tract infection
         subjects affected / exposed
    8 / 147 (5.44%)
    4 / 123 (3.25%)
         occurrences all number
    11
    4
    Viral upper respiratory tract infection
         subjects affected / exposed
    10 / 147 (6.80%)
    4 / 123 (3.25%)
         occurrences all number
    12
    5
    Viral infection
         subjects affected / exposed
    6 / 147 (4.08%)
    11 / 123 (8.94%)
         occurrences all number
    6
    16

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Jul 2009
    The amendment was written to change criteria for which a subject would discontinue due to flare, to that of an unmet ACR30 response. Steroid tapering guidelines were also updated to take into account a loss of ACR 30 response.
    03 Nov 2009
    The main purpose of this amendment was to clarify the eligibility criteria for subjects who rolled over from Study CACZ885G2301 (EudraCT number: 2008-005479-82) and CACZ885G2305 (EudraCT number: 2008-005476-27); to clarify the ACR response calculation and align it with the CAC885G2305 and CACZ885G2301 studies; and to indicate the planned end of study visit date.
    19 Jan 2010
    The main purpose of this amendment was to allow subjects with elevated CRP levels to initiate and continue tapering their corticosteroid dose. Additional inclusion criteria were added to allow responders from CACZ885G2301 (EudraCT number: 2008-005479-82) Part I who flared in Part II to be eligible for study entry.
    03 Jan 2011
    The amendment described the implementation of an adjudication committee for macrophage activation syndrome (MAS) and the follow-up procedures for MAS cases identified in the study.
    26 Oct 2011
    A new canakinumab treatment-naive subject cohort with active SJIA with and without fever was included in the study. The addition of this cohort aimed to i) increase the safety database by capturing key data on infections, genetic biomarkers and risk of MAS; ii) provide safety and efficacy information on the subset of subjects without fever who were not enrolled in the core Studies CACZ885G2301 (EudraCT number: 2008-005479-82) and CACZ885G2305 (EudraCT number: 2008-005476-27); iii) provide an alternative, albeit experimental, treatment option to subjects; and iv) enhance the biomarker database for investigation of response characterization.
    28 Mar 2012
    The exclusion criteria were amended to be in alignment with the canakinumab summary of product characteristics (approved canakinumab label in European Union). Subjects were required to maintain contraception use for 3 months after study drug discontinuation and neutropenic subjects at screening were excluded from participating in the study. The study end date was extended to March 2013 to allow time for subjects to roll-over into Study CACZ885G2306 (EudraCT number: 2013-004867-29).
    01 Nov 2012
    This amendment was written to include two independent adjudication committees into the study, to comply with canakinumab Risk Management Plan (RMP). The study end date was extended to December 2014 to allow additional time for subjects to rollover into Study CACZ885G2306 (EudraCT number: 2013-004867-29)

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 00:58:42 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA