Study of Efficacy and Safety of Canakinumab in Japanese Patients With SJIA

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02396212
• Collaborator: (none)
• Enrollment: 19
• Locations: 7
• Arm: 1
• Actual Duration (Months): 38.8
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was a phase III study designed to provide efficacy and safety data for canakinumab administered for at least 48 weeks as subcutaneous (s.c.) injection every 4 weeks (q4wk) in Japanese patients with Systemic Juvenile Idiopathic Arthritis (SJIA). Interim analysis (IA) data at Week 28 and 48 from this study supported a registration submission of canakinumab in the indication of SJIA in Japan.

Condition or Disease	Intervention/Treatment	Phase
Systemic Juvenile Idiopathic Arthritis	Biological: Canakinumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Single-arm, Active-treatment, Efficacy and Safety Study of Canakinumab (ACZ885) Administered for at Least 48 Weeks in Japanese Patients With Systemic Juvenile Idiopathic Arthritis (SJIA)
• Actual Study Start Date: May 7, 2015
• Actual Primary Completion Date: Mar 7, 2017
• Actual Study Completion Date: Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canakinumab All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.	Biological: Canakinumab; canakinumab was provided as a 150 mg/1 mL solution for subcutaneous injection and administered at 4mg/kg every 4 weeks.; Other Names: ACZ885

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved a Minimum Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria [Week 8]

   Minimum Adapted ACR Pediatric 30 criteria is defined as improvement from baseline at least 30% in at least 3 of response variables 1 to 6 in Adapted ACR Pediatric response variables and no intermittent fever (i.e. axillary, oral, or rectal body temperature ≤ 38°C) in the preceding week (variable 7), with no more than one variable 1-6 worsening by more than 30%. Adapted ACR Pediatric response variables consists of following 7 variables: 1. Physician's Global Assessment of disease activity on a 0-100 mm VAS; 2. Parent's or Patient's (if appropriate in age) Global Assessment of Patient's overall wellbeing based upon the 0-100 mm VAS in the Child Health Assessment Questionnaire (CHAQ); 3. Functional ability: CHAQ; 4. Number of joints with active arthritis; 5. Number of joints with limitation of motion; 6. Laboratory measure of inflammation: CRP (mg/L); 7. Absence of intermittent fever due to SJIA during the preceding week.

2. Percentage of Participants With Canakinumab Treatment Who Were Able to Taper Corticosteroids Successfully [Week 28]

   To evaluate the percentage of participants with canakinumab treatment who were able to taper corticosteroids successfully at Week 28

Secondary Outcome Measures

1. Percentage of Participants Who Met the Adapted ACR Pediatric 30/50/70/90/100 Criteria of Canakinumab Over Time [Weeks 4, 8, 28, 48, 96, 144, end of study (EOS) (up to Week 164)]

   Adapted ACR Pediatric 30/50/70/90/100 criteria was assessed based on the following 7 variables: 1. Physician's Global Assessment of disease activity on a 0-100 mm VAS; 2. Parent's or Patient's (if appropriate in age) Global Assessment of Patient's overall wellbeing based upon the 0-100 mm VAS in the CHAQ; 3. Functional ability: CHAQ; 4. Number of joints with active arthritis; 5. Number of joints with limitation of motion; 6. Laboratory measure of inflammation: CRP (mg/L); 7. Absence of intermittent fever due to 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 6 response variables and no intermittent fever in the preceding week (variable 7) with no more than one variable 1-6 worsening by more than 30%.

2. Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Physician's Global Assessment of Disease Activity [Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)]

   ACR component, Physician's Global Assessment of disease activity on a 0 - 100 mm VAS by visit is the first response ACR variable in the ACR pediatric criteria. The VAS scale ranges from no disease activity (0 mm) to very severe disease activity (100 mm). Lower scale indicates decreased disease activity. Change from baseline was calculated by subtracting baseline value from post baseline value.

3. Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: CHAQ: Parent's or Patient's Global Assessment of Patient's Overall Well-being as Part of CHAQ [Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS up to Week 164]

   ACR component, Parent's or Patient's (if appropriate in age)Global Assessment of patient's overall well-being as part of CHAQ on a 0 - 100 mm VAS by visit is the second response variable in the ACR pediatric criteria. The VAS scale ranges from 0-100 mm, from very well (0 mm) to very poor (100 mm). Lower scale indicates improvement of patient's overall well-being. Absolute change is calculated by subtracting baseline value from post baseline value.

4. Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: CHAQ: Functional Ability Score [Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)]

   Disability Score as part of CHAQ per functional ability score (range from 0 to 3) is one of the variable in the ACR ped criteria. The CHAQ was used to assess physical ability & functional status of patients as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activity categories of daily living: dressing & grooming, arising, eating, walking, reaching, personal hygiene, gripping & other "activities". Subjects choose from 4 responses, ranging from 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) & 3 (unable to do). Standard Disability Index (SDI) was computed by summing up the computed scores for each activity category and dividing by the number of categories answered. The lower the response the more positive the results & the higher the response, the less positive the results. Change from baseline was calculated by subtracting baseline value from post baseline value.

5. Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Number of Joints With Active Arthritis [Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)]

   ACR component, Number of joints with active arthritis was assessed as the forth response variables of ACR Pediatric Criteria.

6. Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Number of Joints With Limitation of Motion [Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)]

   ACR component, Number of joints with limitation of motion is the fifth response variable in the ACR ped criteria.

7. Number of Participants Having Fever in the Adapted ACR Pediatric Criteria of Canakinumab Over Time [Baseline, Day 3, Weeks 2, 8, 28, 48, 56, 96, 124, 144, EOS (up to Week 164)]

   ACR component, Number of participants having fever is the seventh response variable in the ACR ped criteria.

8. Percentage Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Standardized C-Reactive Protein (CRP) [Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)]

   ACR component, Standardized CRP is the sixth response variable in the ACR ped criteria. CRP values were standardized to a normal range of 0 to 10 mg/L.

9. Percentage of Participants Who Had Flares With Canakinumab Treatment Over Time [> Day3, to <= Week 124]

   Flare was defined by at least 1 of the following: Reappearance of SJIA-related (e.g., not due to infection) fever (> 38°C) lasting for at least 2 consecutive days &/OR Flare according to the JIA pediatric criteria for flare (all criteria must be met): ≥ 30% worsening in at least 3 of the 6 response variables and ≥ 30% improvement in at not more than 1 of the 6 response variables if the physician's or parent's global assessment is 1of 3 response variables used to define flare, worsening of ≥ 20 mm must be present, if the number of active joints or joints with limitation of motion is one of 3 response variables used to define flare, worsening in ≥ 2 joints must be present if CRP is used to define flare, CRP must be > 30 mg/L

10. Percentage of Participants Who Achieved Inactive Disease (With and Without Duration of Morning Stiffness) With Canakinumab Treatment Over Time [Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)]

    Inactive disease was defined as meeting all of the following: No joints with active arthritis; No fever (body temperature ≤ 38°C); No rheumatoid rash, serositis, splenomegaly, hepatomegaly or generalized lymphadenopathy attributable to JIA; Normal CRP; Physician's global assessment of disease activity score ≤ 10 mm

11. Percentage of Participants With Canakinumab Treatment Who Were Able to Taper Corticosteroids Successfully Over Time [Weeks 28, 48, 96, 144, EOS (up to Week 164)]

    To evaluate the percentage of participants with canakinumab treatment who were able to taper corticosteroids successfully over time

12. Absolute Change From Baseline of Corticosteroids Dose Reduction With Canakinumab Treatment Over Time [Baseline, Weeks 28, 48, 96, 144, EOS (up to Week 164)]

    To evaluate the change from baseline of corticosteroids dose reduction with canakinumab treatment over time

13. Serum Concentration of Canakinumab [Baseline, Weeks 4, 24, 48, 72, 96, EOS (up to Week 164)]

    To evaluate serum concentration (mean, standard deviation) of canakinumab.

14. Pharmacodynamics (PD) Assessment: Total IL-1 Beta [Baseline, Weeks 4, 24, 48, 72, 96, EOS (up to Week 164)]

    To evaluate serum total IL-1 Beta concentration by visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 19 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Confirmed diagnosis of SJIA as per International League Against Rheumatism (ILAR) definition (Petty, et al. 2004) that must have occurred at least 3 months prior to enrollment with an 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: Rash due to SJIA, lymphadenopathy, Hepatomegaly/Splenomegaly, Serositis

• Active disease at the time of baseline 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 epoch and within 1 week before first canakinumab dose

• C-Reactive Protein (CRP) > 30 mg/L(3 mg/dL) (normal range < 10 mg/L(1 mg/dL))

• Negative TB screen (Chest X-ray and T-SPOT test)

Exclusion Criteria:

• With active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infection. Patients with resolved/previous hepatitis B infection (a negative HBs antigen, but a positive anti-HBs antibody and/or anti-HBc antibody).

• With underlying metabolic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromises the patient and /or places the patient at unacceptable risk for participation.

• With neutropenia (absolute neutrophil count < 1500/mm3) at screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Obu	Aichi	Japan	474 8710
2	Novartis Investigative Site	Chiba-city	Chiba	Japan	266-0007
3	Novartis Investigative Site	Kanazawa-city	Ishikawa	Japan	920-8641
4	Novartis Investigative Site	Kagoshima city	Kagoshima	Japan	890 8520
5	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	232-8555
6	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	236-0004
7	Novartis Investigative Site	Sendai-city	Miyagi	Japan	989-3126

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Nov 12, 2014
• Statistical Analysis Plan - Apr 11, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02396212
• Other Study ID Numbers: CACZ885G1301; 2018-002355-15
• First Posted: Mar 24, 2015
• Last Update Posted: Sep 13, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: ACZ885; canakinumab; Juvenile Rheumatoid arthritis (JRA) chronic; systemic inflammatory disorder; painful joints; inflammation of the synovial membrane; auto-immune rheumatoid disease; reactive rheumatoid arthritis; Systemic Juvenile Rheumatoid arthritis (SJRA); Japanese patients
• Additional relevant MeSH terms: Arthritis; Arthritis, Juvenile

Study Results

Participant Flow

Recruitment Details	It was planned to enroll approximately 20 patients in this study. There were19 patients enrolled and data from all patients were analyzed.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Period Title: Overall Study
STARTED	19
COMPLETED	16
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Overall Participants	19
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	9.9 (4.47)
Sex: Female, Male (Count of Participants)
Female	13 68.4%
Male	6 31.6%
Race/Ethnicity, Customized (Number) [Number]
Asian	19 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved a Minimum Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria
Description	Minimum Adapted ACR Pediatric 30 criteria is defined as improvement from baseline at least 30% in at least 3 of response variables 1 to 6 in Adapted ACR Pediatric response variables and no intermittent fever (i.e. axillary, oral, or rectal body temperature ≤ 38°C) in the preceding week (variable 7), with no more than one variable 1-6 worsening by more than 30%. Adapted ACR Pediatric response variables consists of following 7 variables: 1. Physician's Global Assessment of disease activity on a 0-100 mm VAS; 2. Parent's or Patient's (if appropriate in age) Global Assessment of Patient's overall wellbeing based upon the 0-100 mm VAS in the Child Health Assessment Questionnaire (CHAQ); 3. Functional ability: CHAQ; 4. Number of joints with active arthritis; 5. Number of joints with limitation of motion; 6. Laboratory measure of inflammation: CRP (mg/L); 7. Absence of intermittent fever due to SJIA during the preceding week.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Number [Percentage of Participants]	100.0 526.3%

2. Primary Outcome

Title	Percentage of Participants With Canakinumab Treatment Who Were Able to Taper Corticosteroids Successfully
Description	To evaluate the percentage of participants with canakinumab treatment who were able to taper corticosteroids successfully at Week 28
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Number [Percentage of Participants]	73.7 387.9%

3. Secondary Outcome

Title	Percentage of Participants Who Met the Adapted ACR Pediatric 30/50/70/90/100 Criteria of Canakinumab Over Time
Description	Adapted ACR Pediatric 30/50/70/90/100 criteria was assessed based on the following 7 variables: 1. Physician's Global Assessment of disease activity on a 0-100 mm VAS; 2. Parent's or Patient's (if appropriate in age) Global Assessment of Patient's overall wellbeing based upon the 0-100 mm VAS in the CHAQ; 3. Functional ability: CHAQ; 4. Number of joints with active arthritis; 5. Number of joints with limitation of motion; 6. Laboratory measure of inflammation: CRP (mg/L); 7. Absence of intermittent fever due to 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 6 response variables and no intermittent fever in the preceding week (variable 7) with no more than one variable 1-6 worsening by more than 30%.
Time Frame	Weeks 4, 8, 28, 48, 96, 144, end of study (EOS) (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Week 4 adapted ACR Pediatric 30	94.7 498.4%
Week 4 adapted ACR Pediatric 50	94.7 498.4%
Week 4 adapted ACR Pediatric 70	94.7 498.4%
Week 4 adapted ACR Pediatric 90	84.2 443.2%
Week 4 adapted ACR Pediatric 100	47.4 249.5%
Week 8 adapted ACR Pediatric 30	100.0 526.3%
Week 8 adapted ACR Pediatric 50	100.0 526.3%
Week 8 adapted ACR Pediatric 70	100.0 526.3%
Week 8 adapted ACR Pediatric 90	89.5 471.1%
Week 8 adapted ACR Pediatric 100	68.4 360%
Week 28 adapted ACR Pediatric 30	100.0 526.3%
Week 28 adapted ACR Pediatric 50	100.0 526.3%
Week 28 adapted ACR Pediatric 70	100.0 526.3%
Week 28 adapted ACR Pediatric 90	100.0 526.3%
Week 28 adapted ACR Pediatric 100	56.3 296.3%
Week 48 adapted ACR Pediatric 30	100.0 526.3%
Week 48 adapted ACR Pediatric 50	100.0 526.3%
Week 48 adapted ACR Pediatric 70	100.0 526.3%
Week 48 adapted ACR Pediatric 90	87.5 460.5%
Week 48 adapted ACR Pediatric 100	68.8 362.1%
Week 96 adapted ACR Pediatric 30	100.0 526.3%
Week 96 adapted ACR Pediatric 50	100.0 526.3%
Week 96 adapted ACR Pediatric 70	100.0 526.3%
Week 96 adapted ACR Pediatric 90	93.8 493.7%
Week 96 adapted ACR Pediatric 100	62.5 328.9%
Week 144 adapted ACR Pediatric 30	100.0 526.3%
Week 144 adapted ACR Pediatric 50	100.0 526.3%
Week144 adapted ACR Pediatric 70	100.0 526.3%
Week 144 adapted ACR Pediatric 90	100.0 526.3%
Week 144 adapted ACR Pediatric 100	80.0 421.1%
Week EOS adapted ACR Pediatric 30	89.5 471.1%
End of Study (EOS) adapted ACR Pediatric 50	89.5 471.1%
EOS adapted ACR Pediatric 70	89.5 471.1%
EOS adapted ACR Pediatric 90	84.2 443.2%
EOS adapted ACR Pediatric 100	63.2 332.6%

4. Secondary Outcome

Title	Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Physician's Global Assessment of Disease Activity
Description	ACR component, Physician's Global Assessment of disease activity on a 0 - 100 mm VAS by visit is the first response ACR variable in the ACR pediatric criteria. The VAS scale ranges from no disease activity (0 mm) to very severe disease activity (100 mm). Lower scale indicates decreased disease activity. Change from baseline was calculated by subtracting baseline value from post baseline value.
Time Frame	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Week 4	-60.2 (32.27)
Week 8	-62.2 (28.23)
Week 28	-62.2 (28.61)
Week 48	-63.9 (28.81)
Week 96	-63.1 (26.99)
Week 144	-61.0 (37.24)
EOS	-61.4 (31.05)

5. Secondary Outcome

Title	Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: CHAQ: Parent's or Patient's Global Assessment of Patient's Overall Well-being as Part of CHAQ
Description	ACR component, Parent's or Patient's (if appropriate in age)Global Assessment of patient's overall well-being as part of CHAQ on a 0 - 100 mm VAS by visit is the second response variable in the ACR pediatric criteria. The VAS scale ranges from 0-100 mm, from very well (0 mm) to very poor (100 mm). Lower scale indicates improvement of patient's overall well-being. Absolute change is calculated by subtracting baseline value from post baseline value.
Time Frame	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS up to Week 164

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Week 4	-64.4 (40.80)
Week 8	-73.5 (24.05)
Week 28	-71.9 (23.13)
Week 48	-68.6 (28.67)
Week 96	-68.4 (27.72)
Week 144	-72.8 (25.65)
EOS	-68.1 (26.29)

6. Secondary Outcome

Title	Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: CHAQ: Functional Ability Score
Description	Disability Score as part of CHAQ per functional ability score (range from 0 to 3) is one of the variable in the ACR ped criteria. The CHAQ was used to assess physical ability & functional status of patients as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activity categories of daily living: dressing & grooming, arising, eating, walking, reaching, personal hygiene, gripping & other "activities". Subjects choose from 4 responses, ranging from 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) & 3 (unable to do). Standard Disability Index (SDI) was computed by summing up the computed scores for each activity category and dividing by the number of categories answered. The lower the response the more positive the results & the higher the response, the less positive the results. Change from baseline was calculated by subtracting baseline value from post baseline value.
Time Frame	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Week 4	-0.833 (0.7750)
Week 8	-0.912 (0.7338)
Week 28	-0.998 (0.7871)
Week 48	-1.013 (0.7963)
Week 96	-0.951 (0.8381)
Week 144	-1.026 (0.9465)
EOS	-0.938 (0.7682)

7. Secondary Outcome

Title	Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Number of Joints With Active Arthritis
Description	ACR component, Number of joints with active arthritis was assessed as the forth response variables of ACR Pediatric Criteria.
Time Frame	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Week 4	-5.2 (4.87)
Week 8	-6.2 (7.71)
Week 28	-4.4 (3.44)
Week 48	-4.4 (3.44)
Week 96	-4.4 (3.18)
Week 144	-5.2 (2.68)
EOS	-5.6 (8.10)

8. Secondary Outcome

Title	Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Number of Joints With Limitation of Motion
Description	ACR component, Number of joints with limitation of motion is the fifth response variable in the ACR ped criteria.
Time Frame	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Week 4	-3.9 (4.02)
Week 8	-4.2 (4.30)
Week 28	-3.4 (3.79)
Week 48	-3.5 (3.78)
Week 96	-3.4 (3.59)
Week 144	-3.8 (2.86)
EOS	-3.7 (4.81)

9. Secondary Outcome

Title	Number of Participants Having Fever in the Adapted ACR Pediatric Criteria of Canakinumab Over Time
Description	ACR component, Number of participants having fever is the seventh response variable in the ACR ped criteria.
Time Frame	Baseline, Day 3, Weeks 2, 8, 28, 48, 56, 96, 124, 144, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Baseline	19 100%
Day 3	16 84.2%
Week 2	2 10.5%
Week 8	0 0%
Week 28	0 0%
Week 48	0 0%
Week 56	1 5.3%
Week 96	0 0%
Week 124	1 5.3%
Week 144	0 0%
EOS	0 0%

10. Secondary Outcome

Title	Percentage Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Standardized C-Reactive Protein (CRP)
Description	ACR component, Standardized CRP is the sixth response variable in the ACR ped criteria. CRP values were standardized to a normal range of 0 to 10 mg/L.
Time Frame	Baseline, Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Week 4	-89.45 (41.431)
Week 8	-96.95 (6.915)
Week 28	-98.19 (2.567)
Week 48	-97.64 (6.333)
Week 96	-97.95 (3.730)
Week 144	-98.58 (1.330)
EOS	-89.71 (20.717)

11. Secondary Outcome

Title	Percentage of Participants Who Had Flares With Canakinumab Treatment Over Time
Description	Flare was defined by at least 1 of the following: Reappearance of SJIA-related (e.g., not due to infection) fever (> 38°C) lasting for at least 2 consecutive days &/OR Flare according to the JIA pediatric criteria for flare (all criteria must be met): ≥ 30% worsening in at least 3 of the 6 response variables and ≥ 30% improvement in at not more than 1 of the 6 response variables if the physician's or parent's global assessment is 1of 3 response variables used to define flare, worsening of ≥ 20 mm must be present, if the number of active joints or joints with limitation of motion is one of 3 response variables used to define flare, worsening in ≥ 2 joints must be present if CRP is used to define flare, CRP must be > 30 mg/L
Time Frame	> Day3, to <= Week 124

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
>Day 3 =<Week 2	5.3 27.9%
>Week 2 =<Week 4	5.3 27.9%
>Week 4 =<Week 8	5.3 27.9%
>Week 8 =<Week 12	5.6 29.5%
>Week 12 =<Week 16	5.6 29.5%
>Week 92 =<Week 96	6.3 33.2%
>Week 104 =<Week 108	7.7 40.5%
>Week 120 =<Week 124	12.5 65.8%

12. Secondary Outcome

Title	Percentage of Participants Who Achieved Inactive Disease (With and Without Duration of Morning Stiffness) With Canakinumab Treatment Over Time
Description	Inactive disease was defined as meeting all of the following: No joints with active arthritis; No fever (body temperature ≤ 38°C); No rheumatoid rash, serositis, splenomegaly, hepatomegaly or generalized lymphadenopathy attributable to JIA; Normal CRP; Physician's global assessment of disease activity score ≤ 10 mm
Time Frame	Weeks 4, 8, 28, 48, 96, 144, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Week 4	63.2 332.6%
Week 8	63.2 332.6%
Week 28	75.0 394.7%
Week 48	75.0 394.7%
Week 96	75.0 394.7%
Week 144	80.0 421.1%
EOS	68.4 360%

13. Secondary Outcome

Title	Percentage of Participants With Canakinumab Treatment Who Were Able to Taper Corticosteroids Successfully Over Time
Description	To evaluate the percentage of participants with canakinumab treatment who were able to taper corticosteroids successfully over time
Time Frame	Weeks 28, 48, 96, 144, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Week 28	87.5
Week 48	81.3
Week 96	87.5
Week 144	100.0
EOS	66.7

14. Secondary Outcome

Title	Absolute Change From Baseline of Corticosteroids Dose Reduction With Canakinumab Treatment Over Time
Description	To evaluate the change from baseline of corticosteroids dose reduction with canakinumab treatment over time
Time Frame	Baseline, Weeks 28, 48, 96, 144, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Week 28	-0.133 (0.1676)
Week 48	-0.195 (0.2317)
Week 96	-0.226 (0.2618)
Week 144	-0.296 (0.2545)
EOS	-0.171 (0.2334)

15. Secondary Outcome

Title	Serum Concentration of Canakinumab
Description	To evaluate serum concentration (mean, standard deviation) of canakinumab.
Time Frame	Baseline, Weeks 4, 24, 48, 72, 96, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Baseline	0.01 (0.05)
Week 4	15.7 (5.19)
Week 24	31.3 (11.5)
Week 48	31.1 (9.08)
Week 72	30.6 (8.95)
Week 96	29.5 (8.49)
EOS	28.3 (6.41)

16. Secondary Outcome

Title	Pharmacodynamics (PD) Assessment: Total IL-1 Beta
Description	To evaluate serum total IL-1 Beta concentration by visit.
Time Frame	Baseline, Weeks 4, 24, 48, 72, 96, EOS (up to Week 164)

Outcome Measure Data

Analysis Population Description

The FAS consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
Measure Participants	19
Baseline	0.72 (0.97)
Week 4	49.8 (36.3)
Week 24	85.2 (61.6)
Week 48	81.2 (62.0)
Week 72	75.3 (36.6)
Week 96	74.4 (35.9)
EOS	101 (89.1)

Adverse Events

Time Frame	Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to approximately 39 months.
Arm/Group Title	Canakinumab 4 mg/kg Every 4 Weeks
Arm/Group Description	All patients received canakinumab (ACZ885) as open-label study medication. Patients were administered canakinumab 4 mg/kg every 4 weeks. The maximal total single dose of canakinumab allowed was 300 mg.
All Cause Mortality
	Canakinumab 4 mg/kg Every 4 Weeks
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Serious Adverse Events
	Canakinumab 4 mg/kg Every 4 Weeks
	Affected / at Risk (%)	# Events
Total	10/19 (52.6%)
Blood and lymphatic system disorders
Histiocytosis haematophagic	3/19 (15.8%)
Endocrine disorders
Adrenal insufficiency	2/19 (10.5%)
General disorders
Pyrexia	2/19 (10.5%)
Infections and infestations
Epstein-Barr virus infection	1/19 (5.3%)
Gastroenteritis	1/19 (5.3%)
Influenza	2/19 (10.5%)
Pharyngitis	1/19 (5.3%)
Varicella	1/19 (5.3%)
Viral infection	1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Still's disease	6/19 (31.6%)
Nervous system disorders
Altered state of consciousness	1/19 (5.3%)
Psychiatric disorders
Somatic symptom disorder	1/19 (5.3%)
Other (Not Including Serious) Adverse Events
	Canakinumab 4 mg/kg Every 4 Weeks
	Affected / at Risk (%)	# Events
Total	19/19 (100%)
Blood and lymphatic system disorders
Anaemia	1/19 (5.3%)
Leukopenia	1/19 (5.3%)
Lymphadenitis	1/19 (5.3%)
Lymphadenopathy	1/19 (5.3%)
Cardiac disorders
Ventricular extrasystoles	1/19 (5.3%)
Ear and labyrinth disorders
Motion sickness	1/19 (5.3%)
Endocrine disorders
Adrenal insufficiency	2/19 (10.5%)
Eye disorders
Chalazion	1/19 (5.3%)
Conjunctivitis allergic	2/19 (10.5%)
Gastrointestinal disorders
Abdominal pain	2/19 (10.5%)
Colitis	1/19 (5.3%)
Constipation	6/19 (31.6%)
Dental caries	1/19 (5.3%)
Diarrhoea	2/19 (10.5%)
Enterocolitis	2/19 (10.5%)
Vomiting	1/19 (5.3%)
General disorders
Chest discomfort	1/19 (5.3%)
Injection site pain	1/19 (5.3%)
Injection site reaction	5/19 (26.3%)
Malaise	1/19 (5.3%)
Pyrexia	1/19 (5.3%)
Vessel puncture site pain	1/19 (5.3%)
Hepatobiliary disorders
Hepatic function abnormal	5/19 (26.3%)
Hepatic steatosis	1/19 (5.3%)
Hyperbilirubinaemia	1/19 (5.3%)
Immune system disorders
Allergy to arthropod sting	1/19 (5.3%)
Seasonal allergy	1/19 (5.3%)
Infections and infestations
Angular cheilitis	1/19 (5.3%)
Bronchitis	4/19 (21.1%)
Gastroenteritis	6/19 (31.6%)
Gastroenteritis viral	2/19 (10.5%)
Herpes zoster	1/19 (5.3%)
Hordeolum	4/19 (21.1%)
Impetigo	1/19 (5.3%)
Influenza	4/19 (21.1%)
Lice infestation	1/19 (5.3%)
Nasopharyngitis	12/19 (63.2%)
Otitis media acute	1/19 (5.3%)
Pharyngitis	3/19 (15.8%)
Rhinitis	1/19 (5.3%)
Skin infection	1/19 (5.3%)
Upper respiratory tract infection	4/19 (21.1%)
Viral infection	1/19 (5.3%)
Viral pharyngitis	1/19 (5.3%)
Injury, poisoning and procedural complications
Arthropod bite	2/19 (10.5%)
Arthropod sting	1/19 (5.3%)
Contusion	1/19 (5.3%)
Fall	1/19 (5.3%)
Ligament sprain	4/19 (21.1%)
Investigations
Alanine aminotransferase increased	4/19 (21.1%)
Amylase increased	1/19 (5.3%)
Aspartate aminotransferase increased	1/19 (5.3%)
Blood cholesterol increased	1/19 (5.3%)
Blood creatine phosphokinase decreased	1/19 (5.3%)
Blood creatine phosphokinase increased	1/19 (5.3%)
Blood creatinine increased	1/19 (5.3%)
Blood glucose increased	1/19 (5.3%)
Blood lactate dehydrogenase increased	1/19 (5.3%)
Blood uric acid increased	1/19 (5.3%)
Intraocular pressure increased	1/19 (5.3%)
White blood cell count decreased	1/19 (5.3%)
Metabolism and nutrition disorders
Hyperalbuminaemia	2/19 (10.5%)
Hyperamylasaemia	1/19 (5.3%)
Hypercholesterolaemia	1/19 (5.3%)
Hyperglycaemia	2/19 (10.5%)
Hyperlipidaemia	2/19 (10.5%)
Hyperuricaemia	1/19 (5.3%)
Hypocalcaemia	1/19 (5.3%)
Hypoproteinaemia	1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/19 (10.5%)
Back pain	1/19 (5.3%)
Joint range of motion decreased	1/19 (5.3%)
Limb discomfort	1/19 (5.3%)
Musculoskeletal pain	2/19 (10.5%)
Musculoskeletal stiffness	1/19 (5.3%)
Myalgia	3/19 (15.8%)
Neck pain	3/19 (15.8%)
Pain in extremity	1/19 (5.3%)
Still's disease	2/19 (10.5%)
Tenosynovitis	1/19 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Histiocytic necrotising lymphadenitis	1/19 (5.3%)
Nervous system disorders
Headache	6/19 (31.6%)
Neuropathy peripheral	1/19 (5.3%)
Tremor	1/19 (5.3%)
Psychiatric disorders
Depression	1/19 (5.3%)
Insomnia	1/19 (5.3%)
Reproductive system and breast disorders
Vulvovaginal pruritus	1/19 (5.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/19 (5.3%)
Epistaxis	4/19 (21.1%)
Nasal obstruction	1/19 (5.3%)
Oropharyngeal pain	1/19 (5.3%)
Pneumomediastinum	1/19 (5.3%)
Skin and subcutaneous tissue disorders
Acne	1/19 (5.3%)
Alopecia	1/19 (5.3%)
Blister	1/19 (5.3%)
Dermatitis atopic	3/19 (15.8%)
Dry skin	3/19 (15.8%)
Eczema	4/19 (21.1%)
Eczema asteatotic	1/19 (5.3%)
Haemorrhage subcutaneous	1/19 (5.3%)
Macule	1/19 (5.3%)
Purpura	1/19 (5.3%)
Rash	2/19 (10.5%)
Urticaria	4/19 (21.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.