Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA)
- Conditions
- Systemic Juvenile Idiopathic Arthritis
- Interventions
- Drug: Placebo
- Registration Number
- NCT00886769
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 84
-
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
-
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
-
Male and female patients aged ≥ 2 to < 20 years of age
-
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)
-
Naïve to canakinumab
-
Other protocol defined inclusion criteria may apply
Patients who fulfilled one or more of the following criteria were not eligible for inclusion in this study:
- Pregnant or nursing (lactating) female patients
- 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
- History of hypersensitivity to study drug or to biologics.
- Diagnosis of active macrophage-activation syndrome (MAS) (Ravelli, Magni-Manzoni and Pistorio 2005) within the last 6 months
- 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
- Other protocol defined exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Canakinumab 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 Placebo Patients received a single dose matching placebo of canakinumab on day 1.
- Primary Outcome Measures
Name Time Method Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria Baseline, Day 15, Day 29 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)
- Secondary Outcome Measures
Name Time Method Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria Baseline, Day 15, Day 29 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)
Percentage of Patients Achieving the Adapted ACR Pediatric 70 Baseline, Day 15, Day 29 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)
Percentage of Patients Achieving the Adapted ACR Pediatric 90 Baseline, Day 15, Day 29 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)
Percentage of Patients Achieving the Adapted ACR Pediatric 100 baseline, Day 15, Day 29 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
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) Baseline, Day 15 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.
Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ Baseline, Day 29 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.
Percentage of Patients Who Had Body Temperature ≤ 38°C Day 3 Body temperature was derived from vital signs evaluation. No conversion of body temperature was performed, no matter how it was measured.
Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50) Over 4 week study period (Baseline, Day 15, Day 29) 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.
Change in Disability Score Over Time by Use of the CHAQ At 4 week study period 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.
Trial Locations
- Locations (17)
St. Barnabas Ambulatory Care Center
🇺🇸Livingston, New Jersey, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Arkansas Children's Hospital Research Inst
🇺🇸Little Rock, Arkansas, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Tufts New England Medical Center-Dept. of Allergy
🇺🇸Boston, Massachusetts, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Legacy Emanual Research
🇺🇸Portland, Oregon, United States
Children's Hospital/Neurology
🇺🇸Cinncinati, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Legacy Emanuel Hospital
🇺🇸Portland, Oregon, United States
Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Specially For Children
🇺🇸Austin, Texas, United States
Novartis Investigative Site
🇹🇷Izmir, Turkey
Novartis Investigative site
🇬🇧Oxford, United Kingdom
University of Louisville
🇺🇸Louisville, Kentucky, United States