NCT00889863 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2012-10-16

This two-part study assessed the sustained efficacy of canakinumab in the double-blind Part II and the ability to taper steroids in the open label Part I.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Part II: Survival Estimate of Time to Flare

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outcome · POSTED

Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic

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outcome · POSTED

Part I: Percentage of Participants on Steroids at the Start of 1c Who Were Able to Taper Steroids by the End of Part 1c

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outcome · POSTED

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

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outcome · POSTED

Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein

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outcome · POSTED

Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein

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outcome · POSTED

Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a

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outcome · POSTED

Part II: Survival Analysis of Time to a Worsening in American College of Rheumatology (ACR) Response

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outcome · POSTED

Part I: Change in Disability Over Time in the Child Health Assessment Questionnaire-Disability Index (CHAQ-DI) From Baseline to End of Part I

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outcome · POSTED

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

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outcome · POSTED

Part I: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)

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outcome · POSTED

Part II: Change in Health Related Quality of Life Over Time by Child Health Questionnaire (CHQ-PF50)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Confirmed diagnosis of systemic juvenile idiopathic arthritis as per International League Against Rheumatism (ILAR) definition that must have occurred at least 2 months prior to enrollment with onset of disease \< 16 years of age. -Arthritis in one or more joints with or preceded by fever of at least 2 weeks duration that is documented to be daily for at least 3 days with accompanying symptoms * Active disease at the time of enrollment defined as follows: * At least 2 joints with active arthritis (using American College of rheumatology) ACR definition of active joint) * Documented spiking, intermittent fever (body temperature \> 38oC) for at least 1 day during the screening period within 1 week before first study drug dose * C-reactive protein \> 30 mg/L (normal range \< 10 mg/L) * No concomitant use of second line agents such as disease-modifying and/ or immunosuppressive drugs will be allowed with the exception of: * Stable dose of methotrexate for at least 8 weeks prior to the screening visit, and/or folic/folinic acid per standard medical practice * Stable dose of no more than one non-steroidal anti-inflammatory drug for at least 2 weeks prior to the screening visit * Stable dose of steroid treatment \< or = to 1.0 mg/kg/day in 1-2 doses per day of oral prednisone or equivalent Exclusion criteria: * Diagnosis of active macrophage-activation syndrome (MAS) within the last 6 months * Risk factors for tuberculosis * Patients with active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of HIV infection, Hepatitis B and Hepatitis C infection Other protocol inclusion/exclusion criteria may apply
healthy Volunteers: false
maximum Age: 19 Years
minimum Age: 2 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

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.
intervention Names
Drug: canakinumab
label
Canakinumab
type
EXPERIMENTAL
description
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.
intervention Names
Drug: placebo
label
Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Canakinumab
description
Canakinumab 4 mg/kg dose subcutaneous injection supplied as 6 mL glass vials each containing 150 mg canakinumab as a lyophilized cake.
name
canakinumab
type
DRUG
arm Group Labels
Placebo
description
Placebo powder matching canakinumab supplied as 6 mL glass vials containing a lyophilized cake for subcutaneous injection every 4 weeks in Part II.
name
placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: QUADRUPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 177
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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.
measure
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
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.
measure
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)

secondary Outcomes

measure
Part I: Percentage of Patients on Steroids at Study Start Who Reached a Steroid Dose ≤0.2 mg/kg at End of Part Ic
time Frame
28 Weeks
measure
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)
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%
measure
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
description
Duration in days in the study to the first minimum adapted ACR Pediatric 50 criteria and a normal (\<10mg/L) C-Reactive Protein
measure
Part I: Time to First Minimum American College of Rheumatology (ACR50) and Normal C-Reactive Protein
time Frame
Baseline, Week 32
description
Duration in days in the study to the first minimum adapted ACR Pediatric 70 criteria and a normal (\<10mg/L) C-Reactive Protein
measure
Part I: Time to First Minimum American College of Rheumatology (ACR70) and Normal C-Reactive Protein
time Frame
Baseline, Week 32
measure
Part I: Percentage of Participants With Body Temperature ≤ 38 Degrees Celsius at Day 3 in Part 1a
time Frame
Day 3
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
measure
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)
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.
measure
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)
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.
measure
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)
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.
measure
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)
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.
measure
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)

Full study description

brief Summary: This two-part study assessed the sustained efficacy of canakinumab in the double-blind Part II and the ability to taper steroids in the open label Part I.

Source references

references

citation
Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat NM, Horneff G, Kasapcopur O, Schneider R, Anton J, Barash J, Berner R, Corona F, Cuttica R, Fouillet-Desjonqueres M, Fischbach M, Foster HE, Foell D, Radominski SC, Ramanan AV, Trauzeddel R, Unsal E, Levy J, Vritzali E, Martini A, Lovell DJ; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Canakinumab in patients with systemic juvenile idiopathic arthritis and active systemic features: results from the 5-year long-term extension of the phase III pivotal trials. Ann Rheum Dis. 2018 Dec;77(12):1710-1719. doi: 10.1136/annrheumdis-2018-213150. Epub 2018 Sep 29.
pmid
30269054
type
DERIVED
citation
Brachat AH, Grom AA, Wulffraat N, Brunner HI, Quartier P, Brik R, McCann L, Ozdogan H, Rutkowska-Sak L, Schneider R, Gerloni V, Harel L, Terreri M, Houghton K, Joos R, Kingsbury D, Lopez-Benitez JM, Bek S, Schumacher M, Valentin MA, Gram H, Abrams K, Martini A, Lovell DJ, Nirmala NR, Ruperto N; Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy. Arthritis Res Ther. 2017 Jan 23;19(1):13. doi: 10.1186/s13075-016-1212-x.
pmid
28115015
type
DERIVED
citation
Grom AA, Ilowite NT, Pascual V, Brunner HI, Martini A, Lovell D, Ruperto N; Paediatric Rheumatology International Trials Organisation and the Pediatric Rheumatology Collaborative Study Group; Leon K, Lheritier K, Abrams K. Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Canakinumab. Arthritis Rheumatol. 2016 Jan;68(1):218-28. doi: 10.1002/art.39407.
pmid
26314396
type
DERIVED
citation
Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, Brik R, McCann L, Kasapcopur O, Rutkowska-Sak L, Schneider R, Berkun Y, Calvo I, Erguven M, Goffin L, Hofer M, Kallinich T, Oliveira SK, Uziel Y, Viola S, Nistala K, Wouters C, Cimaz R, Ferrandiz MA, Flato B, Gamir ML, Kone-Paut I, Grom A, Magnusson B, Ozen S, Sztajnbok F, Lheritier K, Abrams K, Kim D, Martini A, Lovell DJ; PRINTO; PRCSG. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012 Dec 20;367(25):2396-406. doi: 10.1056/NEJMoa1205099.
pmid
23252526
type
DERIVED