Flare Prevention Study of Canakinumab in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 2)

This study has been completed.
Sponsor:
Collaborator:
Pediatric Rheumatology International Trials Organization
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00889863
First received: April 21, 2009
Last updated: September 13, 2012
Last verified: September 2012
Results First Received: September 12, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Systemic Juvenile Idiopathic Arthritis With Active Flare
Interventions: Drug: canakinumab
Drug: placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.
Placebo Participants in Part II received placebo matching canakinumab subcutaneous injection every 4 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Participant Flow for 2 periods

Period 1:   Part I: Open Label
    Canakinumab     Placebo  
STARTED     177     0 [1]
Entered Part Ia     145     0  
Entered Part Ib     142     0  
Entered Part Ic     92 [2]   0  
Entered Part 1d     103     0  
COMPLETED     100     0  
NOT COMPLETED     77     0  
Death                 1                 0  
Adverse Event                 4                 0  
Unsatisfactory therapeutic effect                 72                 0  
[1] No participants received placebo in Part I.
[2] Patients steroid free at study entry entered Part Id directly and did not participate in Part Ic.

Period 2:   Part II: Randomized Double Blind
    Canakinumab     Placebo  
STARTED     50     50  
COMPLETED     39     24  
NOT COMPLETED     11     26  
Adverse Event                 0                 4  
Unsatisfactory therapeutic effect                 11                 20  
Withdrawal by Subject                 0                 1  
Protocol deviation                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Baseline Measures
    Canakinumab  
Number of Participants  
[units: participants]
  177  
Age  
[units: years]
Mean ± Standard Deviation
  8.7  ± 4.46  
Gender  
[units: participants]
 
Female     98  
Male     79  



  Outcome Measures
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1.  Primary:   Part I: Percentage of Patients Who Were on Steroids at Entry Into Part I and Who Were Able to Taper Steroid as Per Protocol in at Least 25% of the Patients Who Entered the Study Taking a Steroid   [ Time Frame: 32 Weeks ]

Measure Type Primary
Measure Title Part I: Percentage of Patients Who Were on Steroids at Entry Into Part I and Who Were Able to Taper Steroid as Per Protocol in at Least 25% of the Patients Who Entered the Study Taking a Steroid
Measure Description Ability to taper oral steroids: if dose 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 pediatric criterion. Patients on oral steroids at study entry who did not enter Part 1c are considered steroid tapering failures.
Time Frame 32 Weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants from the Full Analysis Set who were taking oral steroids at the beginning of Part I.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab  
Number of Participants Analyzed  
[units: participants]
  128  
Part I: Percentage of Patients Who Were on Steroids at Entry Into Part I and Who Were Able to Taper Steroid as Per Protocol in at Least 25% of the Patients Who Entered the Study Taking a Steroid  
[units: Percentage of participants]
Number ( 90% Confidence Interval )
  44.5  
  ( 37.1 to 52.2 )  

No statistical analysis provided for Part I: Percentage of Patients Who Were on Steroids at Entry Into Part I and Who Were Able to Taper Steroid as Per Protocol in at Least 25% of the Patients Who Entered the Study Taking a Steroid



2.  Primary:   Part II: Survival Estimate of Time to Flare   [ Time Frame: Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks) ]

Measure Type Primary
Measure Title Part II: Survival Estimate of Time to Flare
Measure Description

Kaplan Meier estimate of the probability to experience a flare. Flare was defined as at least 1 of the following.

  • Reappearance of fever (>38°C, lasting for at least 2 consecutive days) not due to infections
  • Flare according to the JIA pediatric criteria for flare (all criteria must have been met):
  • ≥ 30% worsening in at least 3 of the first 6 response variables
  • ≥ 30% improvement in not more than 1 of the first 6 response variables Patients who discontinued the study while in Part II were counted as flared unless they discontinued because of inactive disease for at least 24 weeks in Part II.
Time Frame Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set in Part II

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.
Placebo Participants in Part II received placebo matching canakinumab subcutaneous injection every 4 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  50     50  
Part II: Survival Estimate of Time to Flare  
[units: Days]
Median ( 95% Confidence Interval )
  NA  
  ( NA to NA ) [1]
  236.0  
  ( 141.0 to 449.0 )  
[1] Not observed. Less than 50% participants with a flare.

No statistical analysis provided for Part II: Survival Estimate of Time to Flare



3.  Secondary:   Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic   [ Time Frame: 28 Weeks ]

Measure Type Secondary
Measure Title Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic
Measure Description No text entered.
Time Frame 28 Weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants from the Full Analysis set who were taking oral steroids at the start of the study.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab  
Number of Participants Analyzed  
[units: participants]
  128  
Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
 
steroid free     32.8  
  ( 24.8 to 41.7 )  
>0 and ≤ 0.2 mg/kg/day     18.8  
  ( 12.4 to 26.6 )  

No statistical analysis provided for Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic



4.  Secondary:   Part I: Percentage of Participants on Steroids at the Start of 1c Who Were Able to Taper Steroids by the End of Part 1c   [ Time Frame: Start of Part Ic (After Week 8) to End of Part Ic (Week 28) ]

Measure Type Secondary
Measure Title Part I: Percentage of Participants on Steroids at the Start of 1c Who Were Able to Taper Steroids by the End of Part 1c
Measure Description No text entered.
Time Frame Start of Part Ic (After Week 8) to End of Part Ic (Week 28)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants from the Full Analysis set who were taking oral steroids at the start of Part Ic.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab  
Number of Participants Analyzed  
[units: participants]
  92  
Part I: Percentage of Participants on Steroids at the Start of 1c Who Were Able to Taper Steroids by the End of Part 1c  
[units: Percentage of participants]
Number ( 90% Confidence Interval )
  62.0  
  ( 52.9 to 70.4 )  

No statistical analysis provided for Part I: Percentage of Participants on Steroids at the Start of 1c Who Were Able to Taper Steroids by the End of Part 1c



5.  Secondary:   Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I   [ Time Frame: Baseline, 32 Weeks ]

Measure Type Secondary
Measure Title Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I
Measure Description

Adapted ACR Pediatric 30/50/70/90/100 criteria are defined as meeting all of the following:

  • improvement from baseline of ≥ 30%, ≥ 50%, ≥ 70%, ≥ 90%, or 100%, in at least 3 of the first 6 response variables

    1. Physician’s global assessment of disease activity
    2. CHAQ-patient’s overall well-being
    3. CHAQ-Functional ability
    4. # of joints with active arthritis
    5. # of joints with limitation of motion
    6. C-Reactive Protein.
  • no intermittent fever in the preceding week
  • no more than one of the first 6 response variables worsening by more than 30%
Time Frame Baseline, 32 Weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants from the full analysis set with an assessment at the given time-point.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab  
Number of Participants Analyzed  
[units: participants]
  175  
Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I  
[units: Percentage of participants]
 
Non-Responders     22.9  
ACR 30 Response     77.1  
ACR 50 Response     73.1  
ACR 70 Response     64.6  
ACR 90 Response     51.4  
ACR 100 Response     34.3  

No statistical analysis provided for Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I



6.  Secondary:   Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein   [ Time Frame: Baseline, Week 32 ]

Measure Type Secondary
Measure Title Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein
Measure Description Duration in days in the study to the first minimum adapted ACR Pediatric 50 criteria and a normal (<10mg/L) C-Reactive Protein
Time Frame Baseline, Week 32  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants from the Full Analysis Set Part I with ACR 50 and a Normal CRP.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab  
Number of Participants Analyzed  
[units: participants]
  63  
Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein  
[units: Days]
Mean ± Standard Deviation
  20.4  ± 8.7  

No statistical analysis provided for Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein



7.  Secondary:   Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein   [ Time Frame: Baseline, Week 32 ]

Measure Type Secondary
Measure Title Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein
Measure Description Duration in days in the study to the first minimum adapted ACR Pediatric 70 criteria and a normal (<10mg/L) C-Reactive Protein
Time Frame Baseline, Week 32  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants from the Full Analysis Set Part I with ACR 70 and a Normal CRP.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab  
Number of Participants Analyzed  
[units: participants]
  65  
Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein  
[units: Days]
Mean ± Standard Deviation
  24.5  ± 21.58  

No statistical analysis provided for Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein



8.  Secondary:   Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a   [ Time Frame: Day 3 ]

Measure Type Secondary
Measure Title Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a
Measure Description No text entered.
Time Frame Day 3  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants from the Full Analysis Set Part I with temperature readings at Day 3.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab  
Number of Participants Analyzed  
[units: participants]
  141  
Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
  98.6  
  ( 95.0 to 99.8 )  

No statistical analysis provided for Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a



9.  Secondary:   Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response   [ Time Frame: Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks) ]

Measure Type Secondary
Measure Title Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response
Measure Description

Kaplan Meier estimate of the time in days to the probability of worsening of the ACR response.

ACR response is determined by the following items:

  1. Physician’s global assessment of disease activity
  2. CHAQ-patient’s overall wellbeing
  3. CHAQ-Functional ability
  4. Number of joints with active arthritis
  5. Number of joints with limitation of motion
  6. C-Reactive Protein.
  7. No intermittent fever in the preceding week
Time Frame Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set Part II

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.
Placebo Participants in Part II received placebo matching canakinumab subcutaneous injection every 4 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  50     50  
Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response  
[units: Days]
Median ( 95% Confidence Interval )
  NA  
  ( 171.0 to NA ) [1]
  141.0  
  ( 85.0 to 281.0 )  
[1] Not observed as less than 50% of patients had a worsening of ACR response.

No statistical analysis provided for Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response



10.  Secondary:   Part I: Change in Disability Over Time in the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) From Baseline to End of Part I   [ Time Frame: Baseline, End of Part I (Week 32) ]

Measure Type Secondary
Measure Title Part I: Change in Disability Over Time in the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) From Baseline to End of Part I
Measure Description The childhood health assessment questionnaire, CHAQ was used to assess physical ability and functional status of patients 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 choose from four response categories, ranging from 0(without any difficulty) to 3(unable to do). A negative change indicates improvement.
Time Frame Baseline, End of Part I (Week 32)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants from the Full Analysis Set Part I with data at baseline and End of Part I.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab  
Number of Participants Analyzed  
[units: participants]
  175  
Part I: Change in Disability Over Time in the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) From Baseline to End of Part I  
[units: Score on a scale]
Median ( Full Range )
  -0.8750  
  ( -2.875 to 1.125 )  

No statistical analysis provided for Part I: Change in Disability Over Time in the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) From Baseline to End of Part I



11.  Secondary:   Part II: Change in Disability Over Time by the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI)   [ Time Frame: Start of Part II (Week 32), End of Part II ( total duration-88 weeks) ]

Measure Type Secondary
Measure Title Part II: Change in Disability Over Time by the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI)
Measure Description

CHAQ-DI assessed physical ability and functional status of patients and quality of life. 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and other “activities”. Parents choose from 4 response categories, ranging from 0(without any difficulty) to 3(unable to do).

Repeated measures Analysis of Covariance with treatment group, visit day, prednisone (or equivalent) dose and adapted ACR 70 response reached at the end of Part Id as covariates.

Time Frame Start of Part II (Week 32), End of Part II ( total duration-88 weeks)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis set Part II.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.
Placebo Participants in Part II received placebo matching canakinumab subcutaneous injection every 4 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  50     50  
Part II: Change in Disability Over Time by the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI)  
[units: Score on a scale]
Least Squares Mean ± Standard Error
  0.1184  ± 0.17592     0.1258  ± 0.18241  

No statistical analysis provided for Part II: Change in Disability Over Time by the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI)



12.  Secondary:   Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)   [ Time Frame: Baseline, End of Part I ( Week 32) ]

Measure Type Secondary
Measure Title Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)
Measure Description The CHQ-PF50© is an instrument used to measure Health Related Quality of Life in children 5-18 from the parent's perspective. The questionnaire measures the following concepts: 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. Summaries are provided for Physical Health and Psychosocial Health. Scores range from 0-100. Increase in score represents improvement.
Time Frame Baseline, End of Part I ( Week 32)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants from the Full Analysis Set Part I-age 5 to 18 years.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab  
Number of Participants Analyzed  
[units: participants]
  125  
Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)  
[units: Score on a scale]
Median ( Full Range )
 
Physical Health Score     21.8050  
  ( -21.554 to 62.309 )  
Psychosocial Health Score     8.2223  
  ( -21.710 to 38.854 )  

No statistical analysis provided for Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)



13.  Secondary:   Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)   [ Time Frame: Start Part II (Week 32), End Part II (total duration - 88 Weeks) ]

Measure Type Secondary
Measure Title Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)
Measure Description CHQ-PF50 measures Physical functioning, Role/social emotional, behavior and physical, Bodily pain, General behavior, Mental health, Self-esteem, General health perception, Change in health, Parental impact–emotional, Parental impact–time, Family activities and cohesion. Summaries are provided for Physical Health and Psychosocial Health. An increase in score indicates improvement. Repeated measures Analysis of Covariance change from start of Part II with treatment group, visit day, prednisone(or equivalent) dose and adapted ACR70 Pediatric response reached at the end of Part Id as covariates.
Time Frame Start Part II (Week 32), End Part II (total duration - 88 Weeks)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set Part II-patients aged 5-18 years.

Reporting Groups
  Description
Canakinumab In Part I participants received open label 4 mg/kg canakinumab subcutaneous injection every 4 weeks for up to 32 weeks. For the first 8 weeks Part Ia (4 weeks) and Ib (4 weeks) patients maintained a stable oral steroid dose (prednisone or equivalent) followed by Ic an up to 20 week steroid tapering period and then Id a 4 week stable steroid dose period. Participants were then randomized to receive either 4 mg/kg canakinumab subcutaneous injection or Placebo comparator in Part II and remained on the stable oral steroid dose for 24 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤ 0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤ 0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.
Placebo Participants in Part II received placebo matching canakinumab subcutaneous injection every 4 weeks. At 24 weeks in Part II participants with a >0.2 mg/kg and ≤0.5 mg/kg and no flare could restart steroid tapering. If the steroid dose was ≤0.2 mg/kg participants continued to maintain their current dose for the remainder of Part II.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  39     37  
Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)  
[units: Score on a scale]
Least Squares Mean ± Standard Error
   
Physical Health Score     3.9  ± 2.54     -0.3  ± 2.53  
Psychosocial Health Score     2.5  ± 1.88     -0.5  ± 1.86  

No statistical analysis provided for Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)




  Serious Adverse Events


  Other Adverse Events


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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided by Novartis

Publications automatically indexed to this study:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00889863     History of Changes
Other Study ID Numbers: CACZ885G2301, EudraCT: 2008-005479-82
Study First Received: April 21, 2009
Results First Received: September 12, 2012
Last Updated: September 13, 2012
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Brazil: Ministry of Health
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: Ministry of Health
Norway: Norwegian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Peru: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Denmark: Lægemiddelstyrelsen