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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00891046
Other study ID # CACZ885G2301E1
Secondary ID EudraCT: 2008-00
Status Completed
Phase Phase 3
First received
Last updated
Start date September 2009
Est. completion date December 2014

Study information

Verified date July 2018
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

Status Completed
Enrollment 270
Est. completion date December 2014
Est. primary completion date December 2014
Accepts healthy volunteers No
Gender All
Age group 2 Years to 19 Years
Eligibility Inclusion criteria:

- Patients from study CACZ885G2305 or CACZ885G2301 who achieved an adapted ACR pediatric 30 response 15 days after their initial dose of canakinumab but clinically deteriorated afterwards or a minimum ACR Pediatric 30 response was not maintained after Day 15 and intervention is deemed necessary by the investigator, or Patients in study CACZ885G2301 who are not eligible to enter Part II (withdrawal part) because they were not able to meet the corticosteroid entry criteria , or Responder patients in Part I or Part II who had not flared when CACZ885G2301 was stopped, or CACZ885G2301 patients who were responders in Part I but experienced a flare in Part II.

- Treatment-naïve patients need to meet the following criteria:

- 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

- Male and female patients aged = 2 to < 20 years of age

- Active disease at the time of enrollment defined as having 2 or more of the following:

- Documented spiking, intermittent fever (body temperature > 38°C) for at least 1 day during the screening period and within 1 week before first canakinumab dose

- At least 2 joints with active arthritis

- AND C-reactive protein (CRP) > 30 mg/L (normal range < 10 mg/L) Rash Serositis Lymphadenopathy Hepatosplenomegaly

- Naïve to canakinumab

Other protocol-defined inclusion criteria may apply

Exclusion criteria:

- History of allergy or hypersensitivity to study drug

- With active or recurrent bacterial, fungal or viral infections at time of enrollment

Other protocol inclusion/exclusion criteria may apply

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Canakinumab
Canakinumab

Locations

Country Name City State
Argentina Novartis Investigative Site Caba Buenos Aires
Austria Novartis Investigative Site Vienna
Belgium Novartis Investigative Site Bruxelles
Belgium Novartis Investigative Site Gent
Belgium Novartis Investigative Site Laeken
Belgium Novartis Investigative Site Leuven
Brazil Novartis Investigative Site Curitiba PR
Brazil Novartis Investigative Site Rio de Janeiro RJ
Brazil Novartis Investigative Site Rio de Janeiro RJ
Brazil Novartis Investigative Site São Paulo SP
Canada Novartis Investigative Site Montreal Quebec
Canada Novartis Investigative Site Toronto Ontario
Canada Novartis Investigative Site Vancouver British Columbia
France Novartis Investigative Site Le Kremlin Bicetre
France Novartis Investigative Site Lyon
France Novartis Investigative Site Paris cedex 15
France Novartis Investigative Site Strasbourg
Germany Novartis Investigative Site Bad Bramstedt
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Freiburg
Germany Novartis Investigative Site Garmisch-Partenkirchen
Germany Novartis Investigative Site Gießen
Germany Novartis Investigative Site Hamburg
Germany Novartis Investigative Site Hamburg
Germany Novartis Investigative Site Hannover
Germany Novartis Investigative Site Heidelberg
Germany Novartis Investigative Site Muenster
Germany Novartis Investigative Site Saint Augustin
Germany Novartis Investigative Site Tübingen
Greece Novartis Investigative Site Ampelokipi GR
Greece Novartis Investigative Site Goudi- Athens
Greece Novartis Investigative Site Thessaloniki GR
Hungary Novartis Investigative Site Budapest
Israel Novartis Investigative Site Haifa
Israel Novartis Investigative Site Kfar-Sava
Israel Novartis Investigative Site Petach-Tikva
Israel Novartis Investigative Site Ramat Gan
Israel Novartis Investigative Site Rehovot
Italy Novartis Investigative Site Firenze FI
Italy Novartis Investigative Site Genova GE
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Napoli
Netherlands Novartis Investigative Site Utrecht
Peru Novartis Investigative Site Breña Lima
Poland Novartis Investigative Site Warszawa
Russian Federation Novartis Investigative Site Moscow
Russian Federation Novartis Investigative Site Moscow
Russian Federation Novartis Investigative Site Saint-Petersburg
Spain Novartis Investigative Site Esplugues de Llobregat Barcelona
Spain Novartis Investigative Site Madrid
Spain Novartis Investigative Site Madrid
Spain Novartis Investigative Site Valencia Comunidad Valenciana
Sweden Novartis Investigative Site Stockholm
Switzerland Novartis Investigative Site Lausanne
Turkey Novartis Investigative Site Ankara
Turkey Novartis Investigative Site Balcova / Izmir
Turkey Novartis Investigative Site Fatih / Istanbul
Turkey Novartis Investigative Site Istanbul
United Kingdom Novartis Investigative Site Bath
United Kingdom Novartis Investigative Site Birmingham
United Kingdom Novartis Investigative Site Liverpool
United Kingdom Novartis Investigative Site London
United Kingdom Novartis Investigative Site Manchester
United Kingdom Novartis Investigative Site Newcastle Upon Tyme
United Kingdom Novartis Investigative Site Oxford
United States Novartis Investigative Site Boston Massachusetts
United States Novartis Investigative Site Cincinnati Ohio
United States Novartis Investigative Site Columbus Ohio
United States Novartis Investigative Site Los Angeles California
United States Novartis Investigative Site Louisville Kentucky
United States Novartis Investigative Site Portland Oregon

Sponsors (2)

Lead Sponsor Collaborator
Novartis Pharmaceuticals Pediatric Rheumatology International Trials Organization

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Canada,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Netherlands,  Peru,  Poland,  Russian Federation,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 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)
Primary 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. 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)
Primary 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. 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)
Primary 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%. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Primary 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%. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Primary 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%. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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%. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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). Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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.
Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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). Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
Secondary 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. Baseline up to last assessment (4 years) or date of discontinuation, which ever occurred earlier
See also
  Status Clinical Trial Phase
Completed NCT01304420 - Ultrasonography in Juvenile Idiopathic Arthritis Phase 0
Completed NCT02334748 - A Study of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis or Hereditary Periodic Fevers Who Participated in the CACZ885G2301E1, CACZ885G2306 or CACZ885N2301 Studies Phase 3
Completed NCT01803321 - Study to Evaluate the Safety and Tolerability of Two Doses of Rilonacept in Pediatric Subjects With Active Systemic Juvenile Idiopathic Arthritis (SJIA) Phase 1
Completed NCT00144664 - Study of MRA for Polyarticular Juvenile Idiopathic Arthritis (pJIA) Phase 3
Completed NCT02396212 - Study of Efficacy and Safety of Canakinumab in Japanese Patients With SJIA Phase 3
Completed NCT00144599 - Study of MRA for Systemic Juvenile Idiopathic Arthritis (sJIA) Phase 3
Terminated NCT00886769 - Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA) Phase 3
Completed NCT00144612 - Long-term Treatment Study of MRA for Systemic Juvenile Idiopathic Arthritis (sJIA) Phase 3
Withdrawn NCT01676948 - An Open-label, Multi-arm, Non-comparative Safety and Tolerability Study of Canakinumab (ACZ885) in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA) Phase 3
Recruiting NCT04088396 - A Study of Baricitinib (LY3009104) in Participants From 1 Year to Less Than 18 Years Old With Systemic Juvenile Idiopathic Arthritis (sJIA) Phase 3
Recruiting NCT05027373 - Safety, Tolerability and Pharmacokinetic of Recombinant Anti-IL-1β Humanized Monoclonal Antibody Injection Phase 1

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