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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
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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 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 ]

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) ]

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 ]

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) ]

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 ]

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

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 ]

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

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) ]

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) ]

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) ]

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) ]

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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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