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NCT02396212

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

Completed Phase 3 Results posted Last updated 13 September 2019
What this trial tests

Phase 3 trial testing Canakinumab in Systemic Juvenile Idiopathic Arthritis in 19 participants. Completed in 1 August 2018.

Timeline
7 May 2015
Primary endpoint
7 March 2017
1 August 2018

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment19
Start date7 May 2015
Primary completion7 March 2017
Estimated completion1 August 2018
Sites7 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 2 to 19, any sex, with Systemic Juvenile Idiopathic Arthritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Achieved a Minimum Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria Primary · 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

GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks100.0
Percentage of Participants With Canakinumab Treatment Who Were Able to Taper Corticosteroids Successfully Primary · Week 28

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

GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks73.7
Percentage of Participants Who Met the Adapted ACR Pediatric 30/50/70/90/100 Criteria of Canakinumab Over Time Secondary · 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 (≥) 3

Week 4 adapted ACR Pediatric 30
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks94.7
Week 4 adapted ACR Pediatric 50
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks94.7
Week 4 adapted ACR Pediatric 70
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks94.7
Week 4 adapted ACR Pediatric 90
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks84.2
Week 4 adapted ACR Pediatric 100
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks47.4
Week 8 adapted ACR Pediatric 30
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks100.0
Week 8 adapted ACR Pediatric 50
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks100.0
Week 8 adapted ACR Pediatric 70
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks100.0
Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Physician's Global Assessment of Disease Activity Secondary · 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.

Week 4
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-60.2± 32.27
Week 8
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-62.2± 28.23
Week 28
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-62.2± 28.61
Week 48
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-63.9± 28.81
Week 96
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-63.1± 26.99
Week 144
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-61.0± 37.24
EOS
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-61.4± 31.05
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 Secondary · 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.

Week 4
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-64.4± 40.80
Week 8
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-73.5± 24.05
Week 28
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-71.9± 23.13
Week 48
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-68.6± 28.67
Week 96
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-68.4± 27.72
Week 144
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-72.8± 25.65
EOS
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-68.1± 26.29
Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: CHAQ: Functional Ability Score Secondary · 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 muc

Week 4
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-0.833± 0.7750
Week 8
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-0.912± 0.7338
Week 28
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-0.998± 0.7871
Week 48
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-1.013± 0.7963
Week 96
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-0.951± 0.8381
Week 144
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-1.026± 0.9465
EOS
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-0.938± 0.7682
Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Number of Joints With Active Arthritis Secondary · 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.

Week 4
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-5.2± 4.87
Week 8
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-6.2± 7.71
Week 28
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-4.4± 3.44
Week 48
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-4.4± 3.44
Week 96
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-4.4± 3.18
Week 144
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-5.2± 2.68
EOS
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-5.6± 8.10
Absolute Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Number of Joints With Limitation of Motion Secondary · 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.

Week 4
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-3.9± 4.02
Week 8
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-4.2± 4.30
Week 28
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-3.4± 3.79
Week 48
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-3.5± 3.78
Week 96
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-3.4± 3.59
Week 144
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-3.8± 2.86
EOS
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-3.7± 4.81
Number of Participants Having Fever in the Adapted ACR Pediatric Criteria of Canakinumab Over Time Secondary · 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.

Baseline
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks19
Day 3
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks16
Week 2
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks2
Week 8
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks0
Week 28
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks0
Week 48
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks0
Week 56
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks1
Week 96
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks0
Percentage Change From Baseline in the Adapted ACR Pediatric Criteria of Canakinumab Over Time: ACR Component: Standardized C-Reactive Protein (CRP) Secondary · 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.

Week 4
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-89.45± 41.431
Week 8
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-96.95± 6.915
Week 28
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-98.19± 2.567
Week 48
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-97.64± 6.333
Week 96
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-97.95± 3.730
Week 144
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-98.58± 1.330
EOS
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks-89.71± 20.717
Percentage of Participants Who Had Flares With Canakinumab Treatment Over Time Secondary · > 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

>Day 3 =<Week 2
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks5.3
>Week 2 =<Week 4
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks5.3
>Week 4 =<Week 8
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks5.3
>Week 8 =<Week 12
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks5.6
>Week 12 =<Week 16
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks5.6
>Week 92 =<Week 96
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks6.3
>Week 104 =<Week 108
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks7.7
>Week 120 =<Week 124
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks12.5
Percentage of Participants Who Achieved Inactive Disease (With and Without Duration of Morning Stiffness) With Canakinumab Treatment Over Time Secondary · 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

Week 4
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks63.2
Week 8
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks63.2
Week 28
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks75.0
Week 48
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks75.0
Week 96
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks75.0
Week 144
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks80.0
EOS
GroupValue95% CI
Canakinumab 4 mg/kg Every 4 Weeks68.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to approximately 39 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Canakinumab 4 mg/kg Every 4 Weeks
Serious: 10/19 (53%)
Deaths: 0/19

Serious adverse events (12 terms)

ReactionSystemCanakinumab 4 mg/kg Every …
Still's diseaseMusculoskeletal and connective tissue disorders
Histiocytosis haematophagicBlood and lymphatic system disorders
Adrenal insufficiencyEndocrine disorders
PyrexiaGeneral disorders
InfluenzaInfections and infestations
Epstein-Barr virus infectionInfections and infestations
GastroenteritisInfections and infestations
PharyngitisInfections and infestations
VaricellaInfections and infestations
Viral infectionInfections and infestations
Altered state of consciousnessNervous system disorders
Somatic symptom disorderPsychiatric disorders
Other adverse events (104 terms — click to expand)

ReactionSystemCanakinumab 4 mg/kg Every …
NasopharyngitisInfections and infestations
ConstipationGastrointestinal disorders
GastroenteritisInfections and infestations
HeadacheNervous system disorders
Injection site reactionGeneral disorders
Hepatic function abnormalHepatobiliary disorders
BronchitisInfections and infestations
HordeolumInfections and infestations
InfluenzaInfections and infestations
Upper respiratory tract infectionInfections and infestations
Ligament sprainInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
EpistaxisRespiratory, thoracic and mediastinal disorders
EczemaSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders
PharyngitisInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
Dermatitis atopicSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
Adrenal insufficiencyEndocrine disorders
Conjunctivitis allergicEye disorders
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
EnterocolitisGastrointestinal disorders
Gastroenteritis viralInfections and infestations
Arthropod biteInjury, poisoning and procedural complications
HyperalbuminaemiaMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
HyperlipidaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
Still's diseaseMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
LymphadenitisBlood and lymphatic system disorders
LymphadenopathyBlood and lymphatic system disorders
Ventricular extrasystolesCardiac disorders
Motion sicknessEar and labyrinth disorders

Most-reported serious reactions: Still's disease, Histiocytosis haematophagic, Adrenal insufficiency, Pyrexia, Influenza, Epstein-Barr virus infection, Gastroenteritis, Pharyngitis.

Data from ClinicalTrials.gov NCT02396212 adverse events section.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. IL-1 Family Cytokine Regulation of Vascular Permeability and Angiogenesis.
    Fahey E, Doyle SL. · · 2019 · cited 215× · PMID 31293586 · DOI 10.3389/fimmu.2019.01426
  2. Inflammasomes and Proteostasis Novel Molecular Mechanisms Associated With Atrial Fibrillation.
    Li N, Brundel BJJM. · · 2020 · cited 81× · PMID 32717176 · DOI 10.1161/circresaha.119.316364
  3. Current Models for Development of Disease-Modifying Osteoarthritis Drugs.
    Makarczyk MJ, Gao Q, He Y, Li Z, et al · · 2021 · cited 50× · PMID 33403944 · DOI 10.1089/ten.tec.2020.0309
  4. Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis: 48-week results from an open-label phase III study in Japanese patients.
    Nishimura K, Hara R, Umebayashi H, Takei S, et al · · 2021 · cited 19× · PMID 32552266 · DOI 10.1080/14397595.2020.1783163
  5. Long-term efficacy and safety of canakinumab in the treatment of systemic juvenile idiopathic arthritis in Japanese patients: Results from an open-label Phase III study.
    Iwata N, Nishimura K, Hara R, Imagawa T, et al · · 2023 · cited 8× · PMID 36399020 · DOI 10.1093/mr/roac128
  6. Targeting pyroptosis in inflammatory bowel disease: A potentially effective therapeutic approach.
    Dong WW, Liu T, He LX, He WT. · · 2025 · cited 1× · PMID 41358180 · DOI 10.3748/wjg.v31.i43.111358

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02396212.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing