Trial Outcomes & Findings for Flare Prevention Study of Canakinumab in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA) (NCT NCT00889863)
NCT ID: NCT00889863
Last Updated: 2012-10-16
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
177 participants
Primary outcome timeframe
32 Weeks
Results posted on
2012-10-16
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|---|
|
Part I: Open Label
STARTED
|
177
|
0
|
|
Part I: Open Label
Entered Part Ia
|
145
|
0
|
|
Part I: Open Label
Entered Part Ib
|
142
|
0
|
|
Part I: Open Label
Entered Part Ic
|
92
|
0
|
|
Part I: Open Label
Entered Part 1d
|
103
|
0
|
|
Part I: Open Label
COMPLETED
|
100
|
0
|
|
Part I: Open Label
NOT COMPLETED
|
77
|
0
|
|
Part II: Randomized Double Blind
STARTED
|
50
|
50
|
|
Part II: Randomized Double Blind
COMPLETED
|
39
|
24
|
|
Part II: Randomized Double Blind
NOT COMPLETED
|
11
|
26
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|---|
|
Part I: Open Label
Death
|
1
|
0
|
|
Part I: Open Label
Adverse Event
|
4
|
0
|
|
Part I: Open Label
Unsatisfactory therapeutic effect
|
72
|
0
|
|
Part II: Randomized Double Blind
Adverse Event
|
0
|
4
|
|
Part II: Randomized Double Blind
Unsatisfactory therapeutic effect
|
11
|
20
|
|
Part II: Randomized Double Blind
Withdrawal by Subject
|
0
|
1
|
|
Part II: Randomized Double Blind
Protocol deviation
|
0
|
1
|
Baseline Characteristics
Flare Prevention Study of Canakinumab in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA)
Baseline characteristics by cohort
| Measure |
Canakinumab
n=177 Participants
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.
|
|---|---|
|
Age Continuous
|
8.7 years
STANDARD_DEVIATION 4.46 • n=5 Participants
|
|
Sex: Female, Male
Female
|
98 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
79 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 32 WeeksPopulation: Participants from the Full Analysis Set who were taking oral steroids at the beginning of Part I.
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.
Outcome measures
| Measure |
Canakinumab
n=128 Participants
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.
|
|---|---|---|
|
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
|
44.5 Percentage of participants
Interval 37.1 to 52.2
|
—
|
PRIMARY outcome
Timeframe: Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks)Population: Full Analysis Set in Part II
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.
Outcome measures
| Measure |
Canakinumab
n=50 Participants
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
n=50 Participants
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.
|
|---|---|---|
|
Part II: Survival Estimate of Time to Flare
|
NA Days
Not observed. Less than 50% participants with a flare.
|
236.0 Days
Interval 141.0 to 449.0
|
SECONDARY outcome
Timeframe: 28 WeeksPopulation: Participants from the Full Analysis set who were taking oral steroids at the start of the study.
Outcome measures
| Measure |
Canakinumab
n=128 Participants
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.
|
|---|---|---|
|
Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic
steroid free
|
32.8 Percentage of participants
Interval 24.8 to 41.7
|
—
|
|
Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic
>0 and ≤ 0.2 mg/kg/day
|
18.8 Percentage of participants
Interval 12.4 to 26.6
|
—
|
SECONDARY outcome
Timeframe: Start of Part Ic (After Week 8) to End of Part Ic (Week 28)Population: Participants from the Full Analysis set who were taking oral steroids at the start of Part Ic.
Outcome measures
| Measure |
Canakinumab
n=92 Participants
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.
|
|---|---|---|
|
Part I: Percentage of Participants on Steroids at the Start of 1c Who Were Able to Taper Steroids by the End of Part 1c
|
62.0 Percentage of participants
Interval 52.9 to 70.4
|
—
|
SECONDARY outcome
Timeframe: Baseline, 32 WeeksPopulation: Participants from the full analysis set with an assessment at the given time-point.
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%
Outcome measures
| Measure |
Canakinumab
n=175 Participants
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.
|
|---|---|---|
|
Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I
Non-Responders
|
22.9 Percentage of participants
|
—
|
|
Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I
ACR 90 Response
|
51.4 Percentage of participants
|
—
|
|
Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I
ACR 100 Response
|
34.3 Percentage of participants
|
—
|
|
Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I
ACR 30 Response
|
77.1 Percentage of participants
|
—
|
|
Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I
ACR 50 Response
|
73.1 Percentage of participants
|
—
|
|
Part I: Percentage of Participants With Minimum American College of Rheumatology (ACR) 30/50/70/90/100 at the End of Part I
ACR 70 Response
|
64.6 Percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 32Population: Participants from the Full Analysis Set Part I with ACR 50 and a Normal CRP.
Duration in days in the study to the first minimum adapted ACR Pediatric 50 criteria and a normal (\<10mg/L) C-Reactive Protein
Outcome measures
| Measure |
Canakinumab
n=63 Participants
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.
|
|---|---|---|
|
Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein
|
20.4 Days
Standard Deviation 8.7
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 32Population: Participants from the Full Analysis Set Part I with ACR 70 and a Normal CRP.
Duration in days in the study to the first minimum adapted ACR Pediatric 70 criteria and a normal (\<10mg/L) C-Reactive Protein
Outcome measures
| Measure |
Canakinumab
n=65 Participants
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.
|
|---|---|---|
|
Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein
|
24.5 Days
Standard Deviation 21.58
|
—
|
SECONDARY outcome
Timeframe: Day 3Population: Participants from the Full Analysis Set Part I with temperature readings at Day 3.
Outcome measures
| Measure |
Canakinumab
n=141 Participants
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.
|
|---|---|---|
|
Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a
|
98.6 Percentage of participants
Interval 95.0 to 99.8
|
—
|
SECONDARY outcome
Timeframe: Part II was event driven. The study was stopped when the required number of 37 flares had occurred (88 weeks)Population: Full Analysis Set Part II
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
Outcome measures
| Measure |
Canakinumab
n=50 Participants
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
n=50 Participants
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.
|
|---|---|---|
|
Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response
|
NA Days
Interval 171.0 to
Not observed as less than 50% of patients had a worsening of ACR response.
|
141.0 Days
Interval 85.0 to 281.0
|
SECONDARY outcome
Timeframe: Baseline, End of Part I (Week 32)Population: Participants from the Full Analysis Set Part I with data at baseline and End of Part I.
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.
Outcome measures
| Measure |
Canakinumab
n=175 Participants
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.
|
|---|---|---|
|
Part I: Change in Disability Over Time in the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) From Baseline to End of Part I
|
-0.8750 Score on a scale
Full Range 0.86492 • Interval -2.875 to 1.125
|
—
|
SECONDARY outcome
Timeframe: Start of Part II (Week 32), End of Part II ( total duration-88 weeks)Population: Full Analysis set Part II.
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.
Outcome measures
| Measure |
Canakinumab
n=50 Participants
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
n=50 Participants
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.
|
|---|---|---|
|
Part II: Change in Disability Over Time by the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI)
|
0.1184 Score on a scale
Standard Error 0.17592
|
0.1258 Score on a scale
Standard Error 0.18241
|
SECONDARY outcome
Timeframe: Baseline, End of Part I ( Week 32)Population: Participants from the Full Analysis Set Part I-age 5 to 18 years.
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.
Outcome measures
| Measure |
Canakinumab
n=125 Participants
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.
|
|---|---|---|
|
Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)
Physical Health Score
|
21.8050 Score on a scale
Full Range 16.10377 • Interval -21.554 to 62.309
|
—
|
|
Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)
Psychosocial Health Score
|
8.2223 Score on a scale
Full Range 11.50688 • Interval -21.71 to 38.854
|
—
|
SECONDARY outcome
Timeframe: Start Part II (Week 32), End Part II (total duration - 88 Weeks)Population: Full Analysis Set Part II-patients aged 5-18 years.
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.
Outcome measures
| Measure |
Canakinumab
n=39 Participants
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
n=37 Participants
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.
|
|---|---|---|
|
Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)
Physical Health Score
|
3.9 Score on a scale
Standard Error 2.54
|
-0.3 Score on a scale
Standard Error 2.53
|
|
Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)
Psychosocial Health Score
|
2.5 Score on a scale
Standard Error 1.88
|
-0.5 Score on a scale
Standard Error 1.86
|
Adverse Events
Canakinumab: Part I
Serious events: 15 serious events
Other events: 138 other events
Deaths: 0 deaths
Canakinumab: Part II
Serious events: 6 serious events
Other events: 40 other events
Deaths: 0 deaths
Placebo: Part II
Serious events: 6 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Canakinumab: Part I
n=177 participants at risk
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.
|
Canakinumab: Part II
n=50 participants at risk
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.
|
Placebo: Part II
n=50 participants at risk
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.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Gastrointestinal disorders
Abdominal pain
|
1.1%
2/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Gastrointestinal disorders
Vomiting
|
1.1%
2/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Gastrointestinal disorders
Diarrhoea
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Gastrointestinal disorders
Nausea
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
General disorders
Pyrexia
|
1.7%
3/177
|
0.00%
0/50
|
0.00%
0/50
|
|
General disorders
Fatigue
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
General disorders
Medical device complication
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Hepatobiliary disorders
Hepatitis
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Immune system disorders
Drug hypersensitivity
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Infections and infestations
Acute sinusitis
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Infections and infestations
Adenovirus infection
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Infections and infestations
Gastroenteritis
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Infections and infestations
Gastrointestinal infection
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Infections and infestations
Gastrointestinal viral infection
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Infections and infestations
Lobar pneumonia
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Infections and infestations
Lymph node abscess
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Infections and infestations
Pharyngitis
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Infections and infestations
Pneumonia
|
0.56%
1/177
|
0.00%
0/50
|
2.0%
1/50
|
|
Investigations
C-reactive protein increased
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Investigations
Coagulation test abnormal
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Investigations
Hepatic enzyme increased
|
0.56%
1/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Investigations
Platelet count increased
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Investigations
Serum ferritin increased
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Investigations
White blood cell count increased
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Musculoskeletal and connective tissue disorders
Juvenile arthritis
|
1.1%
2/177
|
0.00%
0/50
|
4.0%
2/50
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Histiocytosis haematophagic
|
2.3%
4/177
|
0.00%
0/50
|
2.0%
1/50
|
|
Nervous system disorders
Headache
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Nervous system disorders
Paraesthesia
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Nervous system disorders
Somnolence
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Psychiatric disorders
Anxiety
|
1.1%
2/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Respiratory, thoracic and mediastinal disorders
Hyperventilation
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Respiratory, thoracic and mediastinal disorders
Lung consolidation
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.56%
1/177
|
0.00%
0/50
|
0.00%
0/50
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/177
|
0.00%
0/50
|
2.0%
1/50
|
|
Gastrointestinal disorders
Oral disorder
|
0.00%
0/177
|
0.00%
0/50
|
2.0%
1/50
|
|
Infections and infestations
Otitis media
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Infections and infestations
Measles
|
0.00%
0/177
|
0.00%
0/50
|
2.0%
1/50
|
|
Infections and infestations
Sepsis
|
0.00%
0/177
|
0.00%
0/50
|
2.0%
1/50
|
|
Infections and infestations
Septic shock
|
0.00%
0/177
|
0.00%
0/50
|
2.0%
1/50
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Injury, poisoning and procedural complications
Traumatic fracture
|
0.00%
0/177
|
2.0%
1/50
|
2.0%
1/50
|
|
Injury, poisoning and procedural complications
Forearm fracture
|
0.00%
0/177
|
0.00%
0/50
|
2.0%
1/50
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Investigations
Haptoglobin decreased
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Investigations
Platelet count decreased
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Investigations
White blood cell count decreased
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Splenic neoplasm malignancy unspecified
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/177
|
0.00%
0/50
|
2.0%
1/50
|
|
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy
|
0.00%
0/177
|
2.0%
1/50
|
0.00%
0/50
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/177
|
0.00%
0/50
|
2.0%
1/50
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/177
|
0.00%
0/50
|
2.0%
1/50
|
Other adverse events
| Measure |
Canakinumab: Part I
n=177 participants at risk
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.
|
Canakinumab: Part II
n=50 participants at risk
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.
|
Placebo: Part II
n=50 participants at risk
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.
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
15.3%
27/177
|
14.0%
7/50
|
14.0%
7/50
|
|
Nervous system disorders
Headache
|
13.0%
23/177
|
6.0%
3/50
|
6.0%
3/50
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.3%
20/177
|
16.0%
8/50
|
12.0%
6/50
|
|
General disorders
Pyrexia
|
10.2%
18/177
|
14.0%
7/50
|
10.0%
5/50
|
|
Infections and infestations
Upper respiratory tract infection
|
10.2%
18/177
|
12.0%
6/50
|
10.0%
5/50
|
|
Gastrointestinal disorders
Vomiting
|
10.2%
18/177
|
2.0%
1/50
|
8.0%
4/50
|
|
Gastrointestinal disorders
Abdominal pain
|
9.6%
17/177
|
12.0%
6/50
|
8.0%
4/50
|
|
Gastrointestinal disorders
Diarrhoea
|
9.6%
17/177
|
2.0%
1/50
|
6.0%
3/50
|
|
Infections and infestations
Rhinitis
|
9.6%
17/177
|
10.0%
5/50
|
14.0%
7/50
|
|
Infections and infestations
Gastroenteritis
|
7.9%
14/177
|
2.0%
1/50
|
2.0%
1/50
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.6%
10/177
|
24.0%
12/50
|
10.0%
5/50
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.1%
9/177
|
4.0%
2/50
|
4.0%
2/50
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.1%
9/177
|
6.0%
3/50
|
2.0%
1/50
|
|
Gastrointestinal disorders
Nausea
|
5.1%
9/177
|
6.0%
3/50
|
2.0%
1/50
|
|
Infections and infestations
Pharyngitis
|
5.1%
9/177
|
2.0%
1/50
|
4.0%
2/50
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.0%
7/177
|
12.0%
6/50
|
8.0%
4/50
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.1%
2/177
|
8.0%
4/50
|
0.00%
0/50
|
|
Infections and infestations
Oral herpes
|
1.7%
3/177
|
8.0%
4/50
|
0.00%
0/50
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.56%
1/177
|
8.0%
4/50
|
4.0%
2/50
|
|
Infections and infestations
Tinea pedis
|
0.00%
0/177
|
6.0%
3/50
|
0.00%
0/50
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/177
|
4.0%
2/50
|
6.0%
3/50
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/177
|
4.0%
2/50
|
8.0%
4/50
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER