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

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ClinicalTrials.gov Identifier: NCT00889863
Recruitment Status : Completed
First Posted : April 29, 2009
Results First Posted : October 16, 2012
Last Update Posted : October 16, 2012
Sponsor:
Collaborator:
Pediatric Rheumatology International Trials Organization
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Systemic Juvenile Idiopathic Arthritis With Active Flare
Interventions Drug: canakinumab
Drug: placebo
Enrollment 177
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Canakinumab Placebo
Hide Arm/Group Description 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. 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.
Period Title: Part I: Open Label
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
Reason Not Completed
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 Title: Part II: Randomized Double Blind
Started 50 50
Completed 39 24
Not Completed 11 26
Reason Not Completed
Adverse Event             0             4
Unsatisfactory therapeutic effect             11             20
Withdrawal by Subject             0             1
Protocol deviation             0             1
Arm/Group Title Canakinumab
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 177
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 177 participants
8.7  (4.46)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants
Female
98
  55.4%
Male
79
  44.6%
1.Primary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set who were taking oral steroids at the beginning of Part I.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 128
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
44.5
(37.1 to 52.2)
2.Primary Outcome
Title Part II: Survival Estimate of Time to Flare
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set in Part II
Arm/Group Title Canakinumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 50 50
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
236.0
(141.0 to 449.0)
[1]
Not observed. Less than 50% participants with a flare.
3.Secondary Outcome
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
Hide Description [Not Specified]
Time Frame 28 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis set who were taking oral steroids at the start of the study.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 128
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
steroid free
32.8
(24.8 to 41.7)
>0 and ≤ 0.2 mg/kg/day
18.8
(12.4 to 26.6)
4.Secondary Outcome
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
Hide Description [Not Specified]
Time Frame Start of Part Ic (After Week 8) to End of Part Ic (Week 28)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis set who were taking oral steroids at the start of Part Ic.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 92
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of participants
62.0
(52.9 to 70.4)
5.Secondary Outcome
Title Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set with an assessment at the given time-point.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 175
Measure Type: Number
Unit of Measure: 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
6.Secondary Outcome
Title Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set Part I with ACR 50 and a Normal CRP.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 63
Mean (Standard Deviation)
Unit of Measure: Days
20.4  (8.7)
7.Secondary Outcome
Title Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set Part I with ACR 70 and a Normal CRP.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 65
Mean (Standard Deviation)
Unit of Measure: Days
24.5  (21.58)
8.Secondary Outcome
Title Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a
Hide Description [Not Specified]
Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set Part I with temperature readings at Day 3.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 141
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
98.6
(95.0 to 99.8)
9.Secondary Outcome
Title Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set Part II
Arm/Group Title Canakinumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 50 50
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(171.0 to NA)
141.0
(85.0 to 281.0)
[1]
Not observed as less than 50% of patients had a worsening of ACR response.
10.Secondary Outcome
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
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set Part I with data at baseline and End of Part I.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 175
Median (Full Range)
Unit of Measure: Score on a scale
-0.8750
(-2.875 to 1.125)
11.Secondary Outcome
Title Part II: Change in Disability Over Time by the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set Part II.
Arm/Group Title Canakinumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 50 50
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
0.1184  (0.17592) 0.1258  (0.18241)
12.Secondary Outcome
Title Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Full Analysis Set Part I-age 5 to 18 years.
Arm/Group Title Canakinumab
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 125
Median (Full Range)
Unit of Measure: Score on a scale
Physical Health Score
21.8050
(-21.554 to 62.309)
Psychosocial Health Score
8.2223
(-21.710 to 38.854)
13.Secondary Outcome
Title Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set Part II-patients aged 5-18 years.
Arm/Group Title Canakinumab Placebo
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 39 37
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Physical Health Score 3.9  (2.54) -0.3  (2.53)
Psychosocial Health Score 2.5  (1.88) -0.5  (1.86)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Canakinumab: Part I Canakinumab: Part II Placebo: Part II
Hide Arm/Group Description 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 received 4 mg/kg canakinumab subcutaneous injection 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. 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.
All-Cause Mortality
Canakinumab: Part I Canakinumab: Part II Placebo: Part II
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Canakinumab: Part I Canakinumab: Part II Placebo: Part II
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/177 (8.47%)   6/50 (12.00%)   6/50 (12.00%) 
Blood and lymphatic system disorders       
Anaemia  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Lymphadenopathy  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Cardiac disorders       
Cardiac arrest  1  0/177 (0.00%)  0/50 (0.00%)  1/50 (2.00%) 
Gastrointestinal disorders       
Abdominal pain  1  2/177 (1.13%)  0/50 (0.00%)  0/50 (0.00%) 
Vomiting  1  2/177 (1.13%)  0/50 (0.00%)  0/50 (0.00%) 
Abdominal pain upper  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Diarrhoea  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Nausea  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Oral disorder  1  0/177 (0.00%)  0/50 (0.00%)  1/50 (2.00%) 
General disorders       
Pyrexia  1  3/177 (1.69%)  0/50 (0.00%)  0/50 (0.00%) 
Fatigue  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Medical device complication  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Hepatobiliary disorders       
Hepatitis  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Immune system disorders       
Drug hypersensitivity  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Infections and infestations       
Acute sinusitis  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Adenovirus infection  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Gastroenteritis  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Gastrointestinal infection  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Gastrointestinal viral infection  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Lobar pneumonia  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Lymph node abscess  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Pharyngitis  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Pneumonia  1  1/177 (0.56%)  0/50 (0.00%)  1/50 (2.00%) 
Otitis media  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Respiratory tract infection  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Measles  1  0/177 (0.00%)  0/50 (0.00%)  1/50 (2.00%) 
Sepsis  1  0/177 (0.00%)  0/50 (0.00%)  1/50 (2.00%) 
Septic shock  1  0/177 (0.00%)  0/50 (0.00%)  1/50 (2.00%) 
Injury, poisoning and procedural complications       
Femur fracture  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Post procedural haemorrhage  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Traumatic fracture  1  0/177 (0.00%)  1/50 (2.00%)  1/50 (2.00%) 
Forearm fracture  1  0/177 (0.00%)  0/50 (0.00%)  1/50 (2.00%) 
Investigations       
C-reactive protein increased  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Coagulation test abnormal  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Hepatic enzyme increased  1  1/177 (0.56%)  1/50 (2.00%)  0/50 (0.00%) 
Platelet count increased  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Serum ferritin increased  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
White blood cell count increased  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Alanine aminotransferase increased  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Aspartate aminotransferase increased  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Haptoglobin decreased  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Platelet count decreased  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
White blood cell count decreased  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Musculoskeletal and connective tissue disorders       
Juvenile arthritis  1  2/177 (1.13%)  0/50 (0.00%)  2/50 (4.00%) 
Arthralgia  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Arthritis  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Pain in extremity  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Histiocytosis haematophagic  1  4/177 (2.26%)  0/50 (0.00%)  1/50 (2.00%) 
Splenic neoplasm malignancy unspecified  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Nervous system disorders       
Headache  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Paraesthesia  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Posterior reversible encephalopathy syndrome  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Somnolence  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Psychiatric disorders       
Anxiety  1  2/177 (1.13%)  0/50 (0.00%)  0/50 (0.00%) 
Renal and urinary disorders       
Renal colic  1  0/177 (0.00%)  0/50 (0.00%)  1/50 (2.00%) 
Respiratory, thoracic and mediastinal disorders       
Hyperventilation  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Interstitial lung disease  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Lung consolidation  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Pulmonary hypertension  1  1/177 (0.56%)  0/50 (0.00%)  0/50 (0.00%) 
Adenoidal hypertrophy  1  0/177 (0.00%)  1/50 (2.00%)  0/50 (0.00%) 
Respiratory failure  1  0/177 (0.00%)  0/50 (0.00%)  1/50 (2.00%) 
Skin and subcutaneous tissue disorders       
Rash maculo-papular  1  0/177 (0.00%)  0/50 (0.00%)  1/50 (2.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Canakinumab: Part I Canakinumab: Part II Placebo: Part II
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   138/177 (77.97%)   40/50 (80.00%)   35/50 (70.00%) 
Gastrointestinal disorders       
Vomiting  1  18/177 (10.17%)  1/50 (2.00%)  4/50 (8.00%) 
Abdominal pain  1  17/177 (9.60%)  6/50 (12.00%)  4/50 (8.00%) 
Diarrhoea  1  17/177 (9.60%)  1/50 (2.00%)  3/50 (6.00%) 
Abdominal pain upper  1  9/177 (5.08%)  2/50 (4.00%)  2/50 (4.00%) 
Nausea  1  9/177 (5.08%)  3/50 (6.00%)  1/50 (2.00%) 
General disorders       
Pyrexia  1  18/177 (10.17%)  7/50 (14.00%)  5/50 (10.00%) 
Immune system disorders       
Seasonal allergy  1  0/177 (0.00%)  2/50 (4.00%)  4/50 (8.00%) 
Infections and infestations       
Nasopharyngitis  1  27/177 (15.25%)  7/50 (14.00%)  7/50 (14.00%) 
Upper respiratory tract infection  1  18/177 (10.17%)  6/50 (12.00%)  5/50 (10.00%) 
Rhinitis  1  17/177 (9.60%)  5/50 (10.00%)  7/50 (14.00%) 
Gastroenteritis  1  14/177 (7.91%)  1/50 (2.00%)  1/50 (2.00%) 
Pharyngitis  1  9/177 (5.08%)  1/50 (2.00%)  2/50 (4.00%) 
Oral herpes  1  3/177 (1.69%)  4/50 (8.00%)  0/50 (0.00%) 
Tinea pedis  1  0/177 (0.00%)  3/50 (6.00%)  0/50 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  10/177 (5.65%)  12/50 (24.00%)  5/50 (10.00%) 
Pain in extremity  1  7/177 (3.95%)  6/50 (12.00%)  4/50 (8.00%) 
Musculoskeletal pain  1  2/177 (1.13%)  4/50 (8.00%)  0/50 (0.00%) 
Nervous system disorders       
Headache  1  23/177 (12.99%)  3/50 (6.00%)  3/50 (6.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  20/177 (11.30%)  8/50 (16.00%)  6/50 (12.00%) 
Skin and subcutaneous tissue disorders       
Eczema  1  9/177 (5.08%)  3/50 (6.00%)  1/50 (2.00%) 
Urticaria  1  1/177 (0.56%)  4/50 (8.00%)  2/50 (4.00%) 
Pruritus  1  0/177 (0.00%)  2/50 (4.00%)  3/50 (6.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00889863     History of Changes
Other Study ID Numbers: CACZ885G2301
EudraCT: 2008-005479-82
First Submitted: April 21, 2009
First Posted: April 29, 2009
Results First Submitted: September 12, 2012
Results First Posted: October 16, 2012
Last Update Posted: October 16, 2012