Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA) (β-SPECIFIC 1)

This study has been terminated.
(recommendation by Data Monitoring Committee)
Sponsor:
Collaborators:
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Southwest Pediatric Nephrology Study Group
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00886769
First received: April 22, 2009
Last updated: March 13, 2012
Last verified: March 2012
Results First Received: November 21, 2011  
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
Interventions: Drug: Canakinumab
Drug: Placebo

  Participant Flow
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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 Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Participant Flow:   Overall Study
    Canakinumab     Placebo  
STARTED     43     41  
COMPLETED     37     4  
NOT COMPLETED     6     37  
Unsatisfactory therapeutic effect                 6                 37  



  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 Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.
Total Total of all reporting groups

Baseline Measures
    Canakinumab     Placebo     Total  
Number of Participants  
[units: participants]
  43     41     84  
Age  
[units: years]
Mean ± Standard Deviation
  8.3  ± 5.08     9.7  ± 4.32     9.0  ± 4.75  
Gender  
[units: participants]
     
Female     27     23     50  
Male     16     18     34  



  Outcome Measures
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1.  Primary:   Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria   [ Time Frame: Baseline, Day 15, Day 29 ]

Measure Type Primary
Measure Title Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
Measure Description Adapted ACR Pediatric 30 criteria determined responders (improved from baseline of at least 30% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2.Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4.Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)
Time Frame Baseline, Day 15, Day 29  
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.
The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.

Reporting Groups
  Description
Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  43     41  
Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria  
[units: percentage of participants]
   
Day 15     83.7     9.8  
Day 29     79.1     9.8  

No statistical analysis provided for Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria



2.  Secondary:   Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria   [ Time Frame: Baseline, Day 15, Day 29 ]

Measure Type Secondary
Measure Title Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria
Measure Description Adapted ACR Pediatric 50 criteria determined responders (improved from baseline of at least 50% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30%) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)
Time Frame Baseline, Day 15, Day 29  
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.
The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.

Reporting Groups
  Description
Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  43     41  
Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria  
[units: percentage of participants]
   
Day 15     67.4     4.9  
Day 29     76.7     4.9  

No statistical analysis provided for Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria



3.  Secondary:   Percentage of Patients Achieving the Adapted ACR Pediatric 70   [ Time Frame: Baseline, Day 15, Day 29 ]

Measure Type Secondary
Measure Title Percentage of Patients Achieving the Adapted ACR Pediatric 70
Measure Description Adapted ACR Pediatric 70 criteria determined responders (improved from baseline of at least 70% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L)
Time Frame Baseline, Day 15, Day 29  
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.
The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.

Reporting Groups
  Description
Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  43     41  
Percentage of Patients Achieving the Adapted ACR Pediatric 70  
[units: percent of participants]
   
Day 15     60.5     2.4  
Day 29     65.1     2.4  

No statistical analysis provided for Percentage of Patients Achieving the Adapted ACR Pediatric 70



4.  Secondary:   Percentage of Patients Achieving the Adapted ACR Pediatric 90   [ Time Frame: Baseline, Day 15, Day 29 ]

Measure Type Secondary
Measure Title Percentage of Patients Achieving the Adapted ACR Pediatric 90
Measure Description Adapted ACR Pediatric 90 criteria determined responders (improved from baseline of at least 90% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L)
Time Frame Baseline, Day 15, Day 29  
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.
The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.

Reporting Groups
  Description
Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  43     41  
Percentage of Patients Achieving the Adapted ACR Pediatric 90  
[units: percent of participants]
   
Day 15     41.9     0  
Day 29     46.5     2.4  

No statistical analysis provided for Percentage of Patients Achieving the Adapted ACR Pediatric 90



5.  Secondary:   Percentage of Patients Achieving the Adapted ACR Pediatric 100   [ Time Frame: baseline, Day 15, Day 29 ]

Measure Type Secondary
Measure Title Percentage of Patients Achieving the Adapted ACR Pediatric 100
Measure Description Adapted ACR Pediatric 100 criteria determined responders (ie improved from baseline of at least 100% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation
Time Frame baseline, Day 15, Day 29  
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.
The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.

Reporting Groups
  Description
Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  43     41  
Percentage of Patients Achieving the Adapted ACR Pediatric 100  
[units: percent of participants]
   
Day 15     32.6     0  
Day 29     32.6     2.4  

No statistical analysis provided for Percentage of Patients Achieving the Adapted ACR Pediatric 100



6.  Secondary:   Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ)   [ Time Frame: Baseline, Day 15 ]

Measure Type Secondary
Measure Title Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ)
Measure Description CHAQ assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from ‘without any difficulty’ (0) to ‘unable to do’ (3). The parent’s or patient’s pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement.
Time Frame Baseline, Day 15  
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.
The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.

Reporting Groups
  Description
Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  43     25  
Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ)  
[units: Units on a scale]
Least Squares Mean ± Standard Error
  20.3  ± 5.08     66.7  ± 6.35  

No statistical analysis provided for Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ)



7.  Secondary:   Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ   [ Time Frame: Baseline, Day 29 ]

Measure Type Secondary
Measure Title Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ
Measure Description CHAQ, assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from ‘without any difficulty’(0) to ‘unable to do’ (3). The parent’s or patient’s pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement.
Time Frame Baseline, Day 29  
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.
The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.

Reporting Groups
  Description
Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  38     7  
Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ  
[units: Units on a scale]
Least Squares Mean ± Standard Error
  20.6  ± -5.59     62.5  ± 9.7  

No statistical analysis provided for Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ



8.  Secondary:   Percentage of Patients Who Had Body Temperature ≤ 38°C   [ Time Frame: Day 3 ]

Measure Type Secondary
Measure Title Percentage of Patients Who Had Body Temperature ≤ 38°C
Measure Description Body temperature was derived from vital signs evaluation. No conversion of body temperature was performed, no matter how it was measured.
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.
The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.

Reporting Groups
  Description
Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  43     38  
Percentage of Patients Who Had Body Temperature ≤ 38°C  
[units: Percent of participants]
  100     86.8  

No statistical analysis provided for Percentage of Patients Who Had Body Temperature ≤ 38°C



9.  Secondary:   Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire – Parent Form (CHQ-PF50)   [ Time Frame: Over 4 week study period (Baseline, Day 15, Day 29) ]

Measure Type Secondary
Measure Title Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire – Parent Form (CHQ-PF50)
Measure Description CHQ-PF50 measures HRQoL in children 5-18 years old from parent’s perspective. Questionnaire completed by parent without input from patient. Total score ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents. Mixed linear model on change from baseline in CHQ-PF50 score with treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Covariance analysis used a repeated measures approach, so all timepoints over time were taken into account.
Time Frame Over 4 week study period (Baseline, Day 15, Day 29)  
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.
The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Observed cases only were analyzed.

Reporting Groups
  Description
Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  28     34  
Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire – Parent Form (CHQ-PF50)  
[units: units on a scale]
Least Squares Mean ± Standard Error
   
CHQ-PF50 physical score     16.9  ± 3.46     4.9  ± 3.97  
CHQ-PF50 psychosocial score     6.2  ± 2.15     -1.1  ± 2.49  

No statistical analysis provided for Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire – Parent Form (CHQ-PF50)



10.  Secondary:   Change in Disability Score Over Time by Use of the CHAQ   [ Time Frame: At 4 week study period ]

Measure Type Secondary
Measure Title Change in Disability Score Over Time by Use of the CHAQ
Measure Description The disability dimension of CHAQ consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from ‘without any difficulty’(0) to ‘unable to do’ (3). Mixed linear model on change from baseline in CHAQ score included treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Negative change indicates improvement.
Time Frame At 4 week study period  
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.
The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.

Reporting Groups
  Description
Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients>37.5 kg) received two sc injections.
Placebo Patients received a single dose matching placebo of canakinumab on day 1.

Measured Values
    Canakinumab     Placebo  
Number of Participants Analyzed  
[units: participants]
  43     41  
Change in Disability Score Over Time by Use of the CHAQ  
[units: Units on a Scale]
Least Squares Mean ± Standard Error
  -0.8  ± 0.15     -0.2  ± 0.20  

No statistical analysis provided for Change in Disability Score Over Time by Use of the CHAQ




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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.


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