An Open-label, Multi-arm, Non-comparative Safety and Tolerability Study of Canakinumab (ACZ885) in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA)
- Conditions
- Systemic Juvenile Idiopathic Arthritis
- Interventions
- Registration Number
- NCT01676948
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This two-part open-label, multi-arm, non-comparative study will collect long-term safety, efficacy and tolerability data from patients who were responsive to canakinumab from study CACZ885G2301E1 (Cohort 1), and from patients who are treatment naïve to canakinumab (Cohort 2). In addition, the effect of inactivated vaccines in an SJIA patient population will be assessed for the development of adequate (protective) antibody levels following immunization according to respective local vaccination guidelines.
Study Part I:
All patients will be treated with canakinumab 4 mg/kg every 4 weeks (or 2 mg/kg every 4 weeks for Cohort 1 patients who are receiving that dose in CACZ885G2301E1) until study end unless discontinuation occurs, or until they qualify for Part II of the study.
Study Part II:
Patients who are eligible will be randomized to receive canakinumab at a reduced dose or prolonged dose interval (see requirements for dose reduction/dose interval prolongation below).
Patients in Cohort 1 receiving 2 mg/kg q4wk in CACZ885G2301E1 will not be randomized but will be part of the treatment arm canakinumab dose reduction if they are eligible.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Canakinumab - Cohort 2, 4mg Canakinumab 4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate) Canakinumab - Cohort 1, 4mg Canakinumab 4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate) Canakinumab - Cohort 1, 2mg Canakinumab 2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate) Canakinumab - Cohort 2, 2mg Canakinumab 2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate) Cohort 2 - canakinumab dose reduction ACZ885 - Cohort 1 - canakinumab dose reduction ACZ885 -
- Primary Outcome Measures
Name Time Method Long-term safety and tolerability of canakinumab and the retention rate of canakinumab-treated patients Days 1 to 533 Outcome Measure Description: The long-term safety and tolerability of canakinumab and the retention rate of canakinumab-treated patients will be evaluated by monitoring of serious adverse events and adverse events leading to discontinuation of study drug.
- Secondary Outcome Measures
Name Time Method The percentage of patients who meet the adapted pediatric ACR, its individual components, and the Juvenile Arthritis Disease Activity Score [JADAS] over time Days 1 to 533 Outcome Measure Description: Patients will be classified into the adapted pediatric ACR categories to characterize their magnitude of efficacy response. JADAS will be derived from physician global assessment, parent/patient global assessment, active joint count and CRP.
The level of systemic corticosteroid tapering achieved in Part I Day 1 to start of Part II Patients will be classified into the following 3 categories: ≥ 0.2 mg/kg at end of Part I, those who reach a corticosteroid dose between \>0-\<0.2 mg/kg and those who reach corticosteroid free regimen.
The level of canakinumab tapering achieved after randomization to the dose reduction arm or dose interval prolongation treatment arm in Part II from start of Part II to Day 533 In the canakinumab dose reduction arm, patients will be classified into the following 3 categories: Number of patients who are able to reach 1mg/kg q4wk at the end of Part II, canakinumab free regimen by the end of Part II and those who come back to 2mg/kg q4wk at the end of Part II.
In the canakinumab dose interval arm, patients will be classified into the following 3 categories: Number of patients who are able to reach 4mg/kg q12wk at the end of Part II, canakinumab-free regimen by the end of Part II and those who come back to 4mg/kg q8wk at the end of Part II.The time to treatment failure in Part II from start of Part II to Day 533 Time to treatment failure (TTF) is defined as time from randomization to the date when the patient's worsened SJIA disease activity requires increasing the doze or shortening the treatment interval of canakinumab or the date the patient is withdrawn from the study due to a safety concern.