NCT00886769 · CITED IN SOURCE DOCUMENTS

Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active 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: TERMINATED
Registry last update: 2017-03-29

This study assessed the initial efficacy and safety of canakinumab over a 4 week period in patients with systemic juvenile idiopathic arthritis (SJIA) having a flare. Response to treatment will be according to the adapted American College of Rheumatology(ACR)Pediatric 30 criteria at Day 15.

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

→

baseline

Baseline characteristics

→

outcome · POSTED

Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria

→

outcome · POSTED

Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria

→

outcome · POSTED

Percentage of Patients Achieving the Adapted ACR Pediatric 70

→

outcome · POSTED

Percentage of Patients Achieving the Adapted ACR Pediatric 90

→

outcome · POSTED

Percentage of Patients Achieving the Adapted ACR Pediatric 100

→

outcome · POSTED

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)

→

outcome · POSTED

Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ

→

outcome · POSTED

Percentage of Patients Who Had Body Temperature ≤ 38°C

→

outcome · POSTED

Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50)

→

outcome · POSTED

Change in Disability Score Over Time by Use of the CHAQ

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria: 1. Confirmed diagnosis of systemic juvenile idiopathic arthritis as per 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/quotidian for at least 3 days and accompanied by one or more of the following: * evanescent nonfixed erythematous rash, * generalized lymph node enlargement, * hepatomegaly and/ or splenomegaly, * serositis 2. Parent's or legal guardian's written informed consent and child's assent, if appropriate, or patient's informed consent for ≥ 18 years of age 3. Male and female patients aged ≥ 2 to \< 20 years of age 4. Active disease at the time of enrollment defined as follows: * At least 2 joints with active arthritis * Documented spiking, intermittent fever (body temperature \> 38°C) for at least 1 day during the screening period within 1 week before first canakinumab/placebo dose * C-reactive protein (CRP) \> 30 mg/L (normal range \< 10 mg/L) 5. Naïve to canakinumab 6. Other protocol defined inclusion criteria may apply Exclusion Criteria: Patients who fulfilled one or more of the following criteria were not eligible for inclusion in this study: 1. Pregnant or nursing (lactating) female patients 2. Female patients having reached sexual maturity unless their career, lifestyle, or sexual orientation precluded intercourse with a male partner and/or they were using an acceptable method of contraception 3. History of hypersensitivity to study drug or to biologics. 4. Diagnosis of active macrophage-activation syndrome (MAS) (Ravelli, Magni-Manzoni and Pistorio 2005) within the last 6 months 5. With active or recurrent bacterial, fungal or viral infection, including patients with evidence of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C infection 6. Other protocol defined 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
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.
intervention Names
Drug: Canakinumab
label
Canakinumab
type
EXPERIMENTAL
description
Patients received a single dose matching placebo of canakinumab on day 1.
intervention Names
Drug: Placebo
label
Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Canakinumab
description
Canakinumab was supplied in individual 6 mL glass vials each containing 150 mg canakinumab powder as a lyophilized cake. Each reconstituted vial provided 150mg of canakinumab per 1 mL.
name
Canakinumab
other Names
ACZ885
type
DRUG
arm Group Labels
Placebo
description
Placebo was provided in individual 6 mL glass vials each containing 150 mg placebo powder matching canakinumab as a lyophilized cake. Each reconstitued vial provided 150mg of placebo per 1 mL.
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: 84
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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)
measure
Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
time Frame
Baseline, Day 15, Day 29

secondary Outcomes

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)
measure
Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria
time Frame
Baseline, Day 15, Day 29
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)
measure
Percentage of Patients Achieving the Adapted ACR Pediatric 70
time Frame
Baseline, Day 15, Day 29
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)
measure
Percentage of Patients Achieving the Adapted ACR Pediatric 90
time Frame
Baseline, Day 15, Day 29
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
measure
Percentage of Patients Achieving the Adapted ACR Pediatric 100
time Frame
baseline, Day 15, Day 29
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.
measure
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
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.
measure
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
description
Body temperature was derived from vital signs evaluation. No conversion of body temperature was performed, no matter how it was measured.
measure
Percentage of Patients Who Had Body Temperature ≤ 38°C
time Frame
Day 3
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.
measure
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)
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.
measure
Change in Disability Score Over Time by Use of the CHAQ
time Frame
At 4 week study period

Full study description

brief Summary: This study assessed the initial efficacy and safety of canakinumab over a 4 week period in patients with systemic juvenile idiopathic arthritis (SJIA) having a flare. Response to treatment will be according to the adapted American College of Rheumatology(ACR)Pediatric 30 criteria at Day 15.

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