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   43865   clinical trials with a EudraCT protocol, of which   7286   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:
    A randomized, double-blind, placebo controlled, withdrawal study of flare prevention of canakinumab (ACZ885) in patients with Systemic Juvenile Idiopathic Arthritis (SJIA) and active systemic manifestations Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.

    Summary
    EudraCT number
    		 2008-005479-82
    Trial protocol
    		 ES   NO   FR   HU   BE   DE   SE   IT   GB   DK   AT   GR   Outside EU/EEA  
    Global end of trial date
    12 Sep 2011

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Jul 2018
    First version publication date
    06 Jul 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CACZ885G2301
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    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
    12 Sep 2011
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Sep 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This was a two-part study, the main objective of Part I was to assess the efficacy of canakinumab, in terms if it allowed tapering of maintenance dose of oral steroids in at least 25% of the study subjects and the main objective of Part II was to demonstrate that the time to flare was higher with canakinumab than with placebo.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Jul 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
    Netherlands: 8
    Country: Number of subjects enrolled
    Norway: 3
    Country: Number of subjects enrolled
    Poland: 4
    Country: Number of subjects enrolled
    Spain: 10
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    United Kingdom: 14
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    Belgium: 10
    Country: Number of subjects enrolled
    France: 23
    Country: Number of subjects enrolled
    Germany: 17
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    Hungary: 8
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    United States: 10
    Country: Number of subjects enrolled
    Brazil: 10
    Country: Number of subjects enrolled
    Canada: 8
    Country: Number of subjects enrolled
    Turkey: 12
    Country: Number of subjects enrolled
    Argentina: 2
    Country: Number of subjects enrolled
    Switzerland: 4
    Country: Number of subjects enrolled
    Israel: 14
    Country: Number of subjects enrolled
    Peru: 3
    Worldwide total number of subjects
    177
    EEA total number of subjects
    114
    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)
    1
    Children (2-11 years)
    128
    Adolescents (12-17 years)
    42
    Adults (18-64 years)
    6
    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 63 centres in 21 countries.

    Pre-assignment
    Screening details
    		 A total of 177 subjects were enrolled into Part I open-label period and 100 subjects were enrolled into Part II double-blind withdrawal period.

    Period 1
    Period 1 title
    Part I
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    As the Part I was an open-label period, this section was not applicable.

    Arms
    Arm title
    		 ACZ885 (Part I)
    Arm description
    		 Subjects received single dose of 4 milligram/kilogram (mg/kg) canakinumab subcutaneous (s.c.) injection every 4 weeks up to maximum of 32 weeks. Part 1 was divided into 4 sub-parts: Part Ia (4 weeks) and Part Ib (4 weeks), subjects were maintained on a stable oral steroid dose (prednisone or equivalent) followed by Part Ic (20 weeks), during which subjects received tapered doses of steroid. In Part Id (4 weeks), subjects again received stable steroid dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Canakinumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Single dose of 4 mg/kg canakinumab s.c. injection every 4 weeks up to maximum of 32 weeks.

    Number of subjects in period 1
    		ACZ885 (Part I)
    Started
    177
    Completed
    100
    Not completed
    77
         Adverse event, non-fatal
    4
         Death
    1
         Unsatisfactory therapeutic effect
    72
    Period 2
    Period 2 title
    Part II
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    The identity of the canakinumab/placebo treatments were concealed by the use of study drugs in the form of syringes filled with reconstituted canakinumab solutions that were identical in appearance. Unblinding was allowed only in the case of subject emergencies, for Data Monitoring Committee (DMC) interim safety review and when the study was completed.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ACZ885 (Part II)
    Arm description
    		 Subjects received 4 mg/kg canakinumab s.c. injection every 4 weeks and remained on stable oral steroid dose for 24 weeks. The maximal total single dose of canakinumab allowed was 300 mg. Any subject who required a dose greater than 150 mg (body weight more than 37.5 kg), received two s.c. injections of canakinumab. Subjects with oral prednisolone dose between 0.2 mg/kg and 0.5 mg/kg and no flare for at least 24 weeks, were allowed to receive tapered doses of prednisolone. If the dose of oral prednisolone was less than or equal to (≤) 0.2 mg/kg, subjects continued to maintain their current dose for the remainder of Part II.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Canakinumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received single dose of 4 mg/kg canakinumab s.c. injection every 4 weeks up to maximum of 75 weeks.

    Arm title
    		 Placebo (Part II)
    Arm description
    		 Subjects in Part II were received placebo matching to canakinumab s.c. injection every 4 weeks up to maximum of 75 weeks. Subjects with oral prednisolone dose between 0.2 mg/kg and 0.5 mg/kg and no flare for at least 24 weeks, were allowed to receive tapered doses of prednisolone. If the dose of oral prednisolone was ≤ 0.2 mg/kg, subjects continued to maintain their current dose for the remainder of Part II.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Single dose of placebo matching to canakinumab s.c injection every 4 weeks up to maximum of 75 weeks.

    Number of subjects in period 2
    		ACZ885 (Part II) Placebo (Part II)
    Started
    50
    50
    Completed
    39
    24
    Not completed
    11
    26
         Consent withdrawn by subject
    -
    1
         Adverse event, non-fatal
    -
    4
         Unsatisfactory therapeutic effect
    11
    20
         Protocol deviation
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    ACZ885 (Part I)
    Reporting group description
    		 Subjects received single dose of 4 milligram/kilogram (mg/kg) canakinumab subcutaneous (s.c.) injection every 4 weeks up to maximum of 32 weeks. Part 1 was divided into 4 sub-parts: Part Ia (4 weeks) and Part Ib (4 weeks), subjects were maintained on a stable oral steroid dose (prednisone or equivalent) followed by Part Ic (20 weeks), during which subjects received tapered doses of steroid. In Part Id (4 weeks), subjects again received stable steroid dose.

    Reporting group values
    		 ACZ885 (Part I) Total
    Number of subjects
    		 177 177
    Age categorical
    Units: Subjects
        2 to < 4 years
    		 21 21
        4 to < 6 years
    		 32 32
        6 to < 12 years
    		 76 76
        12 to < 20 years
    		 48 48
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 8.7 ± 4.46 -
    Gender categorical
    Units: Subjects
        Female
    		 98 98
        Male
    		 79 79

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    ACZ885 (Part I)
    Reporting group description
    		 Subjects received single dose of 4 milligram/kilogram (mg/kg) canakinumab subcutaneous (s.c.) injection every 4 weeks up to maximum of 32 weeks. Part 1 was divided into 4 sub-parts: Part Ia (4 weeks) and Part Ib (4 weeks), subjects were maintained on a stable oral steroid dose (prednisone or equivalent) followed by Part Ic (20 weeks), during which subjects received tapered doses of steroid. In Part Id (4 weeks), subjects again received stable steroid dose.
    Reporting group title
    ACZ885 (Part II)
    Reporting group description
    		 Subjects received 4 mg/kg canakinumab s.c. injection every 4 weeks and remained on stable oral steroid dose for 24 weeks. The maximal total single dose of canakinumab allowed was 300 mg. Any subject who required a dose greater than 150 mg (body weight more than 37.5 kg), received two s.c. injections of canakinumab. Subjects with oral prednisolone dose between 0.2 mg/kg and 0.5 mg/kg and no flare for at least 24 weeks, were allowed to receive tapered doses of prednisolone. If the dose of oral prednisolone was less than or equal to (≤) 0.2 mg/kg, subjects continued to maintain their current dose for the remainder of Part II.

    Reporting group title
    Placebo (Part II)
    Reporting group description
    		 Subjects in Part II were received placebo matching to canakinumab s.c. injection every 4 weeks up to maximum of 75 weeks. Subjects with oral prednisolone dose between 0.2 mg/kg and 0.5 mg/kg and no flare for at least 24 weeks, were allowed to receive tapered doses of prednisolone. If the dose of oral prednisolone was ≤ 0.2 mg/kg, subjects continued to maintain their current dose for the remainder of Part II.

    Primary: Percentage of subjects able to taper oral steroid use from the start of Part I to end of Part Ic

    		 Close Top of page
    End point title
    		 Percentage of subjects able to taper oral steroid use from the start of Part I to end of Part Ic [1]
    End point description
    The ability to taper oral steroids was defined as if dose was reduced from start of Part I to end of Part Ic from >0.8 mg/kg/day to ≤ 0.5 mg/kg/day, or from ≥ 0.5 mg/kg/day and ≤ 0.8 mg/kg/day by at least 0.3 mg/kg, or from any initial dose to ≤ 0.2 mg/kg/day, while maintaining a minimum adapted ACR 30 paediatric criterion (defined as improvement from baseline of ≥ 30% in at least 3 of the first 6 response variables of adapted ACR paediatric criteria; no intermittent fever in the preceding week and no more than one of the first 6 response variables worsening by more than 30%). Subjects on oral steroids at study entry who did not enter Part 1c were considered steroid tapering failures. The analysis was performed in full analysis set (FAS) population, defined as all subjects who received at least one dose of study drug in Part I.
    End point type
    Primary
    End point timeframe
    Day 1 up to Week 28
    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 outcome measure.
    End point values
    		 ACZ885 (Part I)
    Number of subjects analysed
    128
    Units: percentage of subjects
        number (confidence interval 90%)
    44.5 (37.1 to 52.2)
    No statistical analyses for this end point

    Primary: Time to disease flare in Part II

    		 Close Top of page
    End point title
    		 Time to disease flare in Part II
    End point description
    Disease flare was defined if at least one of following criteria was met: 1.Reappearance of fever(>38°C,lasting for at least 2 consecutive days) not due to infections, 2.Flare according to adapted ACR paediatric criteria such as ≥ 30% worsening in at least 3 of first 6 response variables and ≥ 30% improvement in not more than 1 of first 6 response variables. The worsening of response variables was further defined as worsening of ≥20 millimetres(mm) in physician or parent global assessment, worsening in mobility of at least 2 joints and serum C-reactive protein(CRP) level to be more than 30 milligrams/litres(mg/L). Kaplan Meier estimate was used to analyze probability to experience a flare in subject. Flare Analysis was done in FAS II population, defined as all subjects who received at least one dose of study drug in Part II. Here, 99999.9 represents not estimable data becasue EudraCT system is not accepting "NA" for not available/not estimable data.
    End point type
    Primary
    End point timeframe
    Week 32 up to Week 88 (maximum of 37 flare events)
    End point values
    		 ACZ885 (Part II) Placebo (Part II)
    Number of subjects analysed
    50 [2]
    50
    Units: Days
        median (confidence interval 95%)
    99999.9 (99999.9 to 99999.9)
    236 (141 to 449)
    Notes
    [2] - As only 11 events occurred in this arm, median and 95% confidence interval could not be estimated. 
    Statistical analysis title
    		 Time to disease flare in Part II
    Statistical analysis description
    Log-rank test adjusted for stratification factors prednisone (or equivalent) dose and adapted ACR 70 Paediatric response reached at the end of Part Id as covariates.
    Comparison groups
    Placebo (Part II) v ACZ885 (Part II)
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0032 [3]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.36
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 0.75
    Notes
    [3] - Statistically significant on onesided significance level 0.025.

    Secondary: Percentage of subjects who reached a steroid dose ≤0.2 mg/kg at end of Part Ic

    		 Close Top of page
    End point title
    		 Percentage of subjects who reached a steroid dose ≤0.2 mg/kg at end of Part Ic
    End point description
    Successful steroid tapering was achieved if dose was reduced from start of Part Ic to end of Part Ic from >0.8 mg/kg/day to ≤ 0.5 mg/kg/day, or from ≥ 0.5 mg/kg/day and ≤ 0.8 mg/kg/day by at least 0.3 mg/kg, or from any initial dose to ≤ 0.2 mg/kg/day, while maintaining a minimum adapted ACR 30 paediatric criterion. Subjects who were steroid free or who had an oral steroid dose at a level of >0 mg/kg and ≤ 0.2 mg/kg at the end of Part Ic were determined. The analysis was performed in FAS I population.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Week 28
    End point values
    		 ACZ885 (Part I)
    Number of subjects analysed
    92
    Units: percentage of subjects
    number (confidence interval 95%)
        steroid free
    45.7 (35.2 to 56.4)
        > 0 mg/kg and ≤ 0.2 mg/kg
    26.1 (17.5 to 36.3)
    No statistical analyses for this end point

    Secondary: Percentage of subjects on steroids at the start of 1c who were able to taper steroids by the end of part 1c

    		 Close Top of page
    End point title
    		 Percentage of subjects on steroids at the start of 1c who were able to taper steroids by the end of part 1c
    End point description
    Successful steroid tapering was achieved if dose was reduced from start of Part Ic to end of Part Ic from >0.8 mg/kg/day to ≤ 0.5 mg/kg/day, or from ≥ 0.5 mg/kg/day and ≤ 0.8 mg/kg/day by at least 0.3 mg/kg, or from any initial dose to ≤ 0.2 mg/kg/day, while maintaining a minimum adapted ACR 30 paediatric criterion. The analysis was performed in FAS I population, where missing values were imputed using Last observation carried forward (LOCF) technique.
    End point type
    Secondary
    End point timeframe
    Week 8 up to Week 28
    End point values
    		 ACZ885 (Part I)
    Number of subjects analysed
    57
    Units: percentage of subjects
    number (not applicable)
        >0 and ≤ 0.2 mg/kg/day
    21
        Steroid free
    71.9
    No statistical analyses for this end point

    Secondary: Change from baseline in oral steroid dose in successful steroid taperers at end of Part Ic

    		 Close Top of page
    End point title
    		 Change from baseline in oral steroid dose in successful steroid taperers at end of Part Ic
    End point description
    Successful steroid tapering was achieved if dose was reduced from start of Part Ic to end of Part Ic from >0.8 mg/kg/day to ≤ 0.5 mg/kg/day, or from ≥ 0.5 mg/kg/day and ≤ 0.8 mg/kg/day by at least 0.3 mg/kg, or from any initial dose to ≤ 0.2 mg/kg/day, while maintaining a minimum adapted ACR 30 paediatric criterion. Change from baseline was calculated by using the formula = (end of Part Ic value - baseline value). The analysis was performed in FAS I population.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 ACZ885 (Part I)
    Number of subjects analysed
    57
    Units: mg/kg/day
        arithmetic mean (standard deviation)
    -0.299 ± 0.2412
    No statistical analyses for this end point

    Secondary: Percentage of subjects who achieved minimum response of American College of Rheumatology (ACR) pediatric 30/50/70/90/100 criteria at the end of Part I

    		 Close Top of page
    End point title
    		 Percentage of subjects who achieved minimum response of American College of Rheumatology (ACR) pediatric 30/50/70/90/100 criteria at the end of Part I
    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 in the Child Health Assessment Questionnaire (CHAQ); 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 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 temperature ≤ 38°C) in the preceding week (variable 7) and with no more than one variable 1-6 worsening by more than 30%. The analysis was done in FAS I papulation. Here 'Number of subjects analysed' signifies number of subjects with an ACR assessment at the given visit.
    End point type
    Secondary
    End point timeframe
    Week 32
    End point values
    		 ACZ885 (Part I)
    Number of subjects analysed
    175
    Units: percentage of subjects
    number (not applicable)
        Non-Responders
    22.9
        ACR 30
    77.1
        ACR 50
    73.1
        ACR 70
    64.6
        ACR 90
    51.4
        ACR 100
    34.3
    No statistical analyses for this end point

    Secondary: Percentage of subjects with normal body temperature at Day 3

    		 Close Top of page
    End point title
    		 Percentage of subjects with normal body temperature at Day 3
    End point description
    Subjects who had body temperature of less than or equal to 38 degree Celsius were counted. Body temperature was derived from vital signs evaluation and normal body temperature indicated treatment response. The analysis was performed on FAS I population.
    End point type
    Secondary
    End point timeframe
    Day 3
    End point values
    		 ACZ885 (Part I)
    Number of subjects analysed
    141
    Units: percentage of subjects
        number (confidence interval 95%)
    98.6 (95 to 99.8)
    No statistical analyses for this end point

    Secondary: Time to adapted American College of Rheumatology (ACR) pediatric 50 criteria and normal C – Reactive Protein (CRP) during Part I

    		 Close Top of page
    End point title
    		 Time to adapted American College of Rheumatology (ACR) pediatric 50 criteria and normal C – Reactive Protein (CRP) during Part I
    End point description
    Adapted ACR response was defined as more than or equal to (≥) 50% 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 1-6 worsening by more than 30%. Duration in days in the study to the first minimum adapted ACR Paediatric 50 criteria and a normal (<10 mg/L) CRP was determined. The analysis was performed in FAS I population.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Week 32
    End point values
    		 ACZ885 (Part I)
    Number of subjects analysed
    63
    Units: Days
        arithmetic mean (standard deviation)
    20.4 ± 8.7
    No statistical analyses for this end point

    Secondary: Time to adapted American College of Rheumatology (ACR) pediatric 70 criteria and normal C – Reactive Protein (CRP) during Part I

    		 Close Top of page
    End point title
    		 Time to adapted American College of Rheumatology (ACR) pediatric 70 criteria and normal C – Reactive Protein (CRP) during Part I
    End point description
    Adapted ACR response was defined as more than or equal to (≥) 70% 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 1-6 worsening by more than 30%. Duration in days in the study to the first minimum adapted ACR Paediatric 70 criteria and a normal (<10 mg/L) CRP was determined. The analysis was performed in FAS I population.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Week 32
    End point values
    		 ACZ885 (Part I)
    Number of subjects analysed
    65
    Units: Days
        arithmetic mean (standard deviation)
    24.5 ± 21.58
    No statistical analyses for this end point

    Secondary: Change from baseline in disability score assessed with the Child Health Assessment Questionnaire -Disability index (CHAQ-DI) to end of Part I

    		 Close Top of page
    End point title
    		 Change from baseline in disability score assessed with the Child Health Assessment Questionnaire -Disability index (CHAQ-DI) to end of Part I
    End point description
    The CHAQ was used to assess physical ability and functional status of subjects as well as quality of life. The disability dimension consists 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 were choosen from four response categories, ranging from 0 (without any difficulty) to 3(unable to do). Change from baseline was calculated by using the formula = (post-baseline value – baseline value). A negative change indicates improvement. The analysis was performed in FAS I population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 32 (End of Part 1)
    End point values
    		 ACZ885 (Part I)
    Number of subjects analysed
    175
    Units: Units on a scale
        median (full range (min-max))
    -0.875 (-2.875 to 1.125)
    No statistical analyses for this end point

    Secondary: Change from baseline in Health Related Quality of Life (HRQoL) assessed by Child Health Questionnaire Parent Form (CHQ-PF50) to end of Part I

    		 Close Top of page
    End point title
    		 Change from baseline in Health Related Quality of Life (HRQoL) assessed by Child Health Questionnaire Parent Form (CHQ-PF50) to end of Part I
    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 14-concept 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 well-being of subjects. Change from baseline was calculated by using the formula = (post-baseline value – baseline value). The analysis was performed in FAS I population.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 32 (End of Part 1)
    End point values
    		 ACZ885 (Part I)
    Number of subjects analysed
    125
    Units: Units on a scale
    median (full range (min-max))
        CHQ-PF50 physical health score
    21.805 (-21.554 to 62.309)
        CHQ-PF50 psychosocial score
    8.2223 (-21.71 to 38.854)
    No statistical analyses for this end point

    Secondary: Time to a worsening in American College of Rheumatology (ACR) response during Part II

    		 Close Top of page
    End point title
    		 Time to a worsening in American College of Rheumatology (ACR) response during Part II
    End point description
    Adapted ACR Paediatric 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 in the Child Health Assessment Questionnaire (CHAQ); 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. Kaplan Meier estimate was utilized to analyze the time in days to the probability of worsening of the ACR response in subject. The analysis was performed in FAS II population. Here, 99999.9 represents not estimable data becasue EudraCT system is not accepting "NA" for not available/not estimable data.
    End point type
    Secondary
    End point timeframe
    Week 32 up to Week 88 (maximum of 37 flare events)
    End point values
    		 ACZ885 (Part II) Placebo (Part II)
    Number of subjects analysed
    50 [4]
    50
    Units: Days
        median (confidence interval 95%)
    99999.9 (171 to 99999.9)
    141 (85 to 281)
    Notes
    [4] - As only 18 events occurred in this arm, median and upper 95% confidence interval was not estimated.
    No statistical analyses for this end point

    Secondary: Change in disability from Week 32 assessed with the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) to end of Part II

    		 Close Top of page
    End point title
    		 Change in disability from Week 32 assessed with the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) to end of Part II
    End point description
    The CHAQ was used to assess physical ability and functional status of subjects as well as quality of life. The disability dimension consists 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 were choosen from four response categories, ranging from 0 (without any difficulty) to 3(unable to do). Change from baseline was calculated by using the formula = (post-baseline value – baseline value). A negative change indicates improvement. The analysis was performed in FAS II population.
    End point type
    Secondary
    End point timeframe
    Week 32 (start of Part II), Week 88 (end of Part II)
    End point values
    		 ACZ885 (Part II) Placebo (Part II)
    Number of subjects analysed
    50
    50
    Units: Units on a scale
        least squares mean (standard error)
    0.1184 ± 0.17592
    0.1258 ± 0.18241
    No statistical analyses for this end point

    Secondary: Change from baseline in Health Related Quality of Life (HRQoL) assessed by Child Health Questionnaire Parent Form (CHQ-PF50) to end of Part II

    		 Close Top of page
    End point title
    		 Change from baseline in Health Related Quality of Life (HRQoL) assessed by Child Health Questionnaire Parent Form (CHQ-PF50) to end of Part II
    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 14-concept 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 well-being of subjects. Change from baseline was calculated by using the formula = (post-baseline value – baseline value). The analysis was performed in FAS II population.
    End point type
    Secondary
    End point timeframe
    Week 32 (start of Part II), Week 88 (end of Part II)
    End point values
    		 ACZ885 (Part II) Placebo (Part II)
    Number of subjects analysed
    39
    37
    Units: Units on a scale
    least squares mean (standard error)
        CHQ-PF50 physical health score
    3.9 ± 2.54
    0.3 ± 2.53
        CHQ-PF50 psychosocial health score
    2.5 ± 1.88
    0.5 ± 1.86
    No statistical analyses for this end point

    Secondary: Number of subjects with adverse events (AEs), AEs leading to discontinuation, serious adverse events (SAEs), SAEs leading to discontinuation and death

    		 Close Top of page
    End point title
    		 Number of subjects with adverse events (AEs), AEs leading to discontinuation, serious adverse events (SAEs), SAEs leading to discontinuation and death
    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 I (SS I) population and SS II population defined as, all subject who received at least one dose of study drug and had at least one post-treatment safety assessment in Part I and Part II respecively.
    End point type
    Secondary
    End point timeframe
    Baseline (start of study treatment) up to Week 88 (End of Part II)
    End point values
    		 ACZ885 (Part I) ACZ885 (Part II) Placebo (Part II)
    Number of subjects analysed
    177
    50
    50
    Units: Number of subjects
        AEs
    138
    40
    35
        SAEs
    15
    6
    6
        Deaths
    1
    0
    0
        Discontinuation due to any AE including SAE(s)
    5
    0
    6
        Discontinuation due to SAEs
    5
    0
    3
        Discontinuation due to non-serious AEs
    0
    0
    3
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-ACZ885 antibodies at any visit

    		 Close Top of page
    End point title
    		 Number of subjects with anti-ACZ885 antibodies at any visit
    End point description
    Immunogenicity was analyzed by using a bridging ELISA method. Anti-ACZ885 antibodies were captured in solution by combination of biotinylated and ruthenium-labeled forms of ACZ885. Complex formation was subsequently detected by Electro Chemi Luminescence using a Mesoscale Discovery streptavidin plate. The analysis was performed in safety set I (SS I) population and SS II population.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 88 (End of Part II)
    End point values
    		 ACZ885 (Part I) ACZ885 (Part II)
    Number of subjects analysed
    177
    50
    Units: Number of subjects
    0
    0
    No statistical analyses for this end point

    Secondary: Serum concentrations of Canakinumab

    		 Close Top of page
    End point title
    		 Serum concentrations of Canakinumab
    End point description
    Canakinumab concentrations were assessed in serum. The analysis was performed in FAS I population and FAS II population.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Day 3, Day 15, Day 29, Day 57, Week 32, Week 88
    End point values
    		 ACZ885 (Part I) ACZ885 (Part II) Placebo (Part II)
    Number of subjects analysed
    173
    47
    13
    Units: micrograms/millilitres
        arithmetic mean (standard deviation)
    20.114 ± 11.3115
    35.098 ± 14.1822
    6.386 ± 6.5006
    No statistical analyses for this end point

    Secondary: Serum concentration of total Interleukin-1 beta antibody (IL-1)

    		 Close Top of page
    End point title
    		 Serum concentration of total Interleukin-1 beta antibody (IL-1)
    End point description
    Pharmacodynamics of canakinumab was assessed by total IL-1β (sum of free and bound canakinumab) concentration, determined in serum by means of competitive ELISA assay. The analysis was performed in FAS I population and FAS II population.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Day 3, Day 15, Day 29, Day 57, Week 32, Week 88
    End point values
    		 ACZ885 (Part I) ACZ885 (Part II) Placebo (Part II)
    Number of subjects analysed
    172
    46
    12
    Units: picograms/millilitres
        arithmetic mean (standard deviation)
    58.753 ± 58.1004
    56.99 ± 63.6162
    25.073 ± 23.5487
    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
    14.1
    Reporting groups
    Reporting group title
    Part 1 ACZ885
    Reporting group description
    		 Part 1 ACZ885

    Reporting group title
    Part 2 Placebo
    Reporting group description
    		 Part 2 Placebo

    Reporting group title
    Part 2 ACZ885
    Reporting group description
    		 Part 2 ACZ885

    Serious adverse events
    		 Part 1 ACZ885 Part 2 Placebo Part 2 ACZ885
    Total subjects affected by serious adverse events
         subjects affected / exposed
    15 / 177 (8.47%)
    6 / 50 (12.00%)
    6 / 50 (12.00%)
         number of deaths (all causes)
    1
    0
    0
         number of deaths resulting from adverse events
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Histiocytosis haematophagic
         subjects affected / exposed
    4 / 177 (2.26%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Splenic neoplasm malignancy unspecified
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Medical device complication
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 177 (1.69%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Adenoidal hypertrophy
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperventilation
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung consolidation
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 177 (0.00%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 177 (1.13%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coagulation test abnormal
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haptoglobin decreased
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet count increased
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Serum ferritin increased
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    White blood cell count increased
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    0 / 177 (0.00%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic fracture
         subjects affected / exposed
    0 / 177 (0.00%)
    1 / 50 (2.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 177 (0.00%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 177 (1.13%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oral disorder
         subjects affected / exposed
    0 / 177 (0.00%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 177 (1.13%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    0 / 177 (0.00%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    0 / 177 (0.00%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Juvenile arthritis
         subjects affected / exposed
    2 / 177 (1.13%)
    2 / 50 (4.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenovirus infection
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal viral infection
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymph node abscess
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Measles
         subjects affected / exposed
    0 / 177 (0.00%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 177 (0.56%)
    0 / 50 (0.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 177 (0.56%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    1 / 50 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 177 (0.00%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 177 (0.00%)
    1 / 50 (2.00%)
    0 / 50 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part 1 ACZ885 Part 2 Placebo Part 2 ACZ885
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    101 / 177 (57.06%)
    25 / 50 (50.00%)
    36 / 50 (72.00%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    22 / 177 (12.43%)
    3 / 50 (6.00%)
    3 / 50 (6.00%)
         occurrences all number
    40
    22
    5
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    16 / 177 (9.04%)
    5 / 50 (10.00%)
    7 / 50 (14.00%)
         occurrences all number
    24
    6
    8
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 177 (0.00%)
    4 / 50 (8.00%)
    2 / 50 (4.00%)
         occurrences all number
    0
    4
    2
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    15 / 177 (8.47%)
    4 / 50 (8.00%)
    6 / 50 (12.00%)
         occurrences all number
    17
    5
    14
    Diarrhoea
         subjects affected / exposed
    16 / 177 (9.04%)
    3 / 50 (6.00%)
    1 / 50 (2.00%)
         occurrences all number
    22
    4
    7
    Nausea
         subjects affected / exposed
    8 / 177 (4.52%)
    1 / 50 (2.00%)
    3 / 50 (6.00%)
         occurrences all number
    11
    1
    3
    Vomiting
         subjects affected / exposed
    17 / 177 (9.60%)
    4 / 50 (8.00%)
    1 / 50 (2.00%)
         occurrences all number
    21
    4
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    20 / 177 (11.30%)
    6 / 50 (12.00%)
    8 / 50 (16.00%)
         occurrences all number
    23
    6
    9
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    9 / 177 (5.08%)
    1 / 50 (2.00%)
    3 / 50 (6.00%)
         occurrences all number
    9
    2
    3
    Pruritus
         subjects affected / exposed
    0 / 177 (0.00%)
    3 / 50 (6.00%)
    2 / 50 (4.00%)
         occurrences all number
    0
    3
    3
    Urticaria
         subjects affected / exposed
    1 / 177 (0.56%)
    2 / 50 (4.00%)
    4 / 50 (8.00%)
         occurrences all number
    1
    2
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    9 / 177 (5.08%)
    5 / 50 (10.00%)
    12 / 50 (24.00%)
         occurrences all number
    13
    5
    17
    Musculoskeletal pain
         subjects affected / exposed
    2 / 177 (1.13%)
    0 / 50 (0.00%)
    4 / 50 (8.00%)
         occurrences all number
    2
    0
    6
    Pain in extremity
         subjects affected / exposed
    7 / 177 (3.95%)
    4 / 50 (8.00%)
    5 / 50 (10.00%)
         occurrences all number
    8
    4
    6
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    13 / 177 (7.34%)
    1 / 50 (2.00%)
    1 / 50 (2.00%)
         occurrences all number
    14
    2
    1
    Nasopharyngitis
         subjects affected / exposed
    27 / 177 (15.25%)
    7 / 50 (14.00%)
    7 / 50 (14.00%)
         occurrences all number
    37
    14
    11
    Oral herpes
         subjects affected / exposed
    3 / 177 (1.69%)
    0 / 50 (0.00%)
    4 / 50 (8.00%)
         occurrences all number
    5
    0
    5
    Rhinitis
         subjects affected / exposed
    17 / 177 (9.60%)
    7 / 50 (14.00%)
    5 / 50 (10.00%)
         occurrences all number
    21
    15
    6
    Tinea pedis
         subjects affected / exposed
    0 / 177 (0.00%)
    0 / 50 (0.00%)
    3 / 50 (6.00%)
         occurrences all number
    0
    0
    4
    Upper respiratory tract infection
         subjects affected / exposed
    18 / 177 (10.17%)
    5 / 50 (10.00%)
    6 / 50 (12.00%)
         occurrences all number
    24
    5
    10

    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
    Modified the criteria for which a subject discontinued due to flare in Part I, to that of not achieved ACR30 response or not maintained a minimum ACR30 response and the stable steroid dose level that allowed a subject to taper off steroids after 24 weeks in Part II was lowered to a threshold of > 0.2 mg/kg/day. The entry criteria for rollover subjects from the CACZ885G2305 and CACZ885A2203 studies was changed so that the requirement of intermittent fever and CRP > 30 mg/L was not applicable.
    22 Sep 2009
    Changes done to ensure subjects from the study CACZ885A2203 could continue to receive continuous treatment in subsequent phase III studies provided that the subject did not meet the discontinuation criteria of CACZ885A2203 or the safety discontinuation criteria of CACZ885G2301.
    03 Nov 2009
    Modified the study procedures in order to replace “absence of fever” in the secondary objectives with “body temperature ≤ 38°C”; to ensure that subjects were on a stable dose of corticosteroids for at least 3 days prior to baseline; clarified the transition of CACZ885G2305 placebo subjects to the CACZ885G2301 study if they did not maintain a minimum ACR30 response between Days 15 and 29; and clarified the handling of CACZ885A2203 rollover subjects when there was a gap of at least 6 months between the subject’s last dose in CACZ885A2203 and entry into CACZ885G2301.
    19 Jan 2010
    Modified the study procedures for the subjects who were doing well clinically, to avoid unnecessary exposure to higher steroid doses.
    03 Jan 2011
    Modified the criteria to describe the implementation of an adjudication committee for macrophage activation syndrome (MAS) and follow-up to be conducted on MAS cases identified during the study.
    23 May 2011
    Modified the criteria to introduce the possibility performing an interim analysis and adjusted the statistical hypothesis in the statistical methods section for Part I to be fully aligned with the objective.

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.
    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-Mon Apr 29 05:55:18 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA