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

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ClinicalTrials.gov Identifier: NCT02396212
Recruitment Status : Completed
First Posted : March 24, 2015
Results First Posted : September 13, 2019
Last Update Posted : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
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 : March 7, 2017
Actual Study Completion Date : August 1, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Canakinumab

Arms and Interventions
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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 Name: ACZ885


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants Who Achieved a Minimum Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: > 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline, Weeks 4, 24, 48, 72, 96, EOS (up to Week 164) ]
    To evaluate serum total IL-1 Beta concentration by visit.


Eligibility Criteria
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Ages Eligible for Study:   2 Years to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02396212


Locations
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Japan
Novartis Investigative Site
Obu, Aichi, Japan, 474 8710
Novartis Investigative Site
Chiba-city, Chiba, Japan, 266-0007
Novartis Investigative Site
Kanazawa-city, Ishikawa, Japan, 920-8641
Novartis Investigative Site
Kagoshima city, Kagoshima, Japan, 890 8520
Novartis Investigative Site
Yokohama-city, Kanagawa, Japan, 232-8555
Novartis Investigative Site
Yokohama-city, Kanagawa, Japan, 236-0004
Novartis Investigative Site
Sendai-city, Miyagi, Japan, 989-3126
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] November 12, 2014
Statistical Analysis Plan  [PDF] April 11, 2017

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02396212    
Other Study ID Numbers: CACZ885G1301
2018-002355-15 ( EudraCT Number )
First Posted: March 24, 2015    Key Record Dates
Results First Posted: September 13, 2019
Last Update Posted: September 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
URL: http://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( 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:
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Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
 Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases