This open-label extension study will permit patients with Systemic Juvenile Idiopathic Arthritis (SJIA) who previously were responsive to treatment with canakinumab and canakinumab treatment-naïve patients with active SJIA with and without fever to be retreated with 4 mg/kg s.c. every 4 weeks and assessed for continued efficacy and safety until discontinuation or when study CACZ885G2402 is in place at their study center or around March 2013, whichever occurs first. Patients who are steroid-free will be able to taper their canakinumab dose to 2 mg/kg s.c. every 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
270
Canakinumab
Novartis Investigative Site
Los Angeles, California, United States
Novartis Investigative Site
Louisville, Kentucky, United States
Novartis Investigative Site
Boston, Massachusetts, United States
Novartis Investigative Site
Cincinnati, Ohio, United States
Novartis Investigative Site
Columbus, Ohio, United States
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs by Severity, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Treatment Related AEs and SAE
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the participants or require medical or surgical intervention to prevent one of the aforementioned outcomes. Treatment related AEs or SAEs were defined as AEs or SAEs that were suspected to be related to study treatment as per investigator.
Time frame: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
Number of Participants With Anti -ACZ885 Antibodies at Any Visit During the Study
Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system.
Time frame: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
Number of Participants With Clinically Significant Local Injection Site Reactions During the Study
Local injection site tolerability was assessed on the injection site. Each participant was classified into one of the following four categories: 1. no tolerability reactions at any time during the study, 2. mild reaction observed on at least one occasion but no moderate or severe reactions. 3. moderate reaction observed on at least one occasion but no severe reaction. 4. severe reaction observed on at least one occasion.
Time frame: From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants)
Percentage of Participants Previously Treated With Anakinra Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 1-100 millimeter (mm) visual analog scale (VAS); 2. Participants Global Assessment on a 1-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of C-reactive protein (CRP) and 7. Absence of intermittent fever due to severe juvenile idiopathic arthritis (SJIA) during the preceding week. Response was defined as more than or equal to (≥) 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature less than or equal to (≤) 38 °C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants Previously Treated With Tocilizumab Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 0-100 mm VAS; 2. Participants Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of CRP and 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature ≤ 38 °C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants Previously Treated With Other Biologics Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100 at Last Assessment of Study
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 0-100 mm VAS; 2. Participants Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of CRP and 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature ≤ 38 °C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Non--Responders Who Achieved Minimum Response of American College of Rheumatology (ACR) Pediatric 30/50/70/90/100
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 0-100 mm VAS; 2. Participants Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of -CRP and 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever (i.e. body temperature ≤ 38°C) in the preceding week (variable 7) and with no more than one variable 1 to 6, worsening by more than 30%.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants With Minimum Adapted ACR Pediatric ≥ 30 at Baseline Who Achieved Minimum Response of ACR Pediatric 30/50/70/90/100 at Last Assessment of Study
Adapted ACR Paediatric 30/50/70/90 or 100 was assessed based on following 7 variables: 1.Physician's Global Assessment on a 0-100 mm VAS; 2. Participants Global Assessment on a 0-100 mm VAS; 3. Functional ability; 4. Joints count with active arthritis; 5. Joints count with limitation of motion; 6. Laboratory measure of CRP and 7. Absence of intermittent fever due to SJIA during the preceding week. Response was defined as ≥ 30%/50%/70%/90% or 100% improvement in at least 3 of the response variables 1 to 6, no intermittent fever in the preceding week (variable 7) and with no more than one variable 1 to 6 worsening by more than 30%. For minimum adapted ACR paediatric scores, the last measurement recorded from the participant's previous study was considered baseline for the current study.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants Able to Taper Oral Steroid Use or Reached Steroid Free Regimen
Steroid tapering with oral steroids was allowed if the participant achieved an adapted ACR Paediatric 50 response and had no fever. A participant was considered to have tapered steroids successfully, if the steroid dose was reduced from baseline and the participant did not flare and maintained a minimum adapted ACR Paediatric 30 at the last measurement. A participant was considered to have unsuccessfully tapered steroids if the steroid dose was reduced during the study but dose at last assessment was equal to or greater than dose at baseline or; if steroid dose was reduced but the participant did not maintain a minimum adapted ACR Paediatric 30 at the last measurement.
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Novartis Investigative Site
Portland, Oregon, United States
Novartis Investigative Site
CABA, Buenos Aires, Argentina
Novartis Investigative Site
Vienna, Austria
Novartis Investigative Site
Brussels, Belgium
Novartis Investigative Site
Ghent, Belgium
...and 63 more locations
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Number of Participants Who Reduced Their Canakinumab Dose to 2 mg/kg
The canakinumab dose could be reduced from 4 mg/kg to 2 mg/kg in participants who were steroid-free, if requested by the treating physician and agreed by the sponsor. For treatment naive participants , dose reduction was allowed after the participant had received 6 months treatment with canakinumab.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants With Clinical Remission
Clinical remission was defined as at least 6 months of inactive disease or at least 12 months of inactive disease on medication during the extension period. Participants with inactive disease for at least 6 months, but had loss of inactive disease before 12 months were also determined.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Disability, Overall Well-Being and Pain Intensity Scores Based on Child Health Assessment Questionnaire (CHAQ) to Last Assessment of Study
The CHAQ was used to assess physical ability, overall well- being and pain intensity experienced by participants. The CHAQ (disability and well-being) dimension consisted 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". Participants were graded for the response in four categories, ranging from 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) and 3 (unable to do). Participant's pain intensity was assessed by parents and adult participants (18-20 years old) on a VAS scale of 0-100 mm (0 mm: no pain to 100: very severe pain). Change from baseline was calculated by using the formula = (post baseline value - baseline value). For both scales, lower scores indicate increased functional ability.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Health-Related Quality of Life (HRQoL) Over Time Based on Child Health Questionnaire- Parent Form (CHQ-PF50) to Last Assessment of Study
The Child Health Questionnaire - Parent Form (CHQ-PF50) instrument was used to measure HRQoL aged 5 to 18 years from a parent's perspective. This 14 concept questionnaire measured physical and psychosocial health of the participants on following points: 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. Total score ranged from 1-100. Increase in score represented improvement in overall well being of participants. Change from baseline was calculated by using the formula = (post baseline value - baseline value).
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in EuroQual 5 -Dimension Health Status Questionnaire (EQ-5D) Utility Index and Health State Assessment Scores [EQ Visual Analog Scale (EQ-VAS)] to Last Assessment of Study
EQ-5D HRQoL tool was used for participants above 12 years and EQ-5D proxy for 8-11 years. EQ-5D index scores range from -0.11 (worst possible health, worse than dead), to 0 (dead) to 1 (perfect health). Utility based EQ-5D questionnaire provides generic measure of health for clinical and economic appraisal based on 2 parts: EQ-5D descriptive system - 5 dimensions each with 3 levels (1:no, 2:moderate, 3:severe problem) on: mobility (1=0, 2=0.069, 3=0.314), self-care (1=0, 2=0.104, 3=0.214), usual activities (1=0, 2=0.036, 3=0.094), pain/discomfort (1=0, 2=0, 3=0.386) and anxiety/depression (1=0, 2=0.071, 3=0.2). EQ-5D Total score= 1-0.081-(score of level 2 in present)-0.269 (if at least one of level 3 presents). EQ-5D total score: 1=high quality of life; -0.59 worst quality of life; and EQ-VAS - record participant's self-rated health on vertical, visual analog scale as '100=Best and 0=Worst imaginable health state'. Positive change from baseline score indicated improved health status.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Score to Last Assessment of Study
Sleep patterns in children and adolescents aged between 11 and 15 years were determined using PDSS instrument to evaluate whether canakinumab helps in reducing sleepiness in children with SJIA. Participants were assessed on 8 items of PDSS, on a scale of 0 to 4 (0 - never, 1 - seldom, 2- sometimes, 3 - frequently and 4 - always). The sum of all the items was reported as total score with a range of 0-32. Change from baseline was calculated by using the formula = (post baseline value - baseline value). A positive change from baseline score indicated improvement.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Growth Velocity Parameter for Height to Last Assessment of Study
Growth velocity parameter height percentile was determined. Percentile was based on the growth charts smoothed percentile curve released by Centers for Disease control and prevention (CDC) in 2000, by sex and age.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Percentage of Participants With Inactive Disease
Inactive disease was defined as no joints with active arthritis; no fever (body temperature ≤ 38 degree Celsius); no rheumatoid rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to SJIA; normal CRP, and a rating of no disease activity on the Physician's Global Assessment of disease activity (with a best possible score ≤10 mm on the VAS).
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Growth Velocity Parameters to Last Assessment of Study
Growth velocity parameter weight percentile was determined. Percentile was based on the growth charts smoothed percentile curve released by Centers for Disease control and prevention (CDC) in 2000, by sex and age.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Change From Baseline in Growth Velocity Parameter for BMI to Last Assessment of Study
Growth velocity parameter BMI percentile was determined. Percentile was based on the growth charts smoothed percentile curve released by Centers for Disease control and prevention (CDC) in 2000, by sex and age.
Time frame: Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier