An Open-label, Multi-arm, Non-comparative Safety and Tolerability Study of Canakinumab (ACZ885) in Patients With Active Systemic Juvenile Idiopathic Arthritis (SJIA)

NCT01676948 | Withdrawn Phase 3

• 2 other identifiers: CACZ885G24022012-003054-92
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Systemic Juvenile Idiopathic Arthritis

Keywords

SJIA; Systemic Juvenile Idiopathic Arthritis; children; systemic autoinflammatory disease, ACZ885, canakinumab; human monoclonal anti-interleukin-1β (IL-1 β) antibody; hildhood immunizations vaccinations

Outcome Measures

Primary Outcomes (1)

• Long-term safety and tolerability of canakinumab and the retention rate of canakinumab-treated patients

  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.

  Days 1 to 533

Secondary Outcomes (4)

• 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

• The level of systemic corticosteroid tapering achieved in Part I

  Day 1 to start of Part II

• 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

• The time to treatment failure in Part II

  from start of Part II to Day 533

Study Arms (6)

Canakinumab - Cohort 1, 2mg

EXPERIMENTAL

2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate)

Drug: Canakinumab

Canakinumab - Cohort 1, 4mg

EXPERIMENTAL

4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate)

Drug: Canakinumab

Canakinumab - Cohort 2, 2mg

EXPERIMENTAL

2 mg/kg q4wk (followed by taper to 1 mg/kg q4wk and drug discontinuation if appropriate)

Drug: Canakinumab

Canakinumab - Cohort 2, 4mg

EXPERIMENTAL

4 mg/kg q8wk (followed by taper to 4 mg/kg q12wk and drug discontinuation if appropriate)

Drug: Canakinumab

Cohort 2 - canakinumab dose reduction

EXPERIMENTAL

Drug: ACZ885

Cohort 1 - canakinumab dose reduction

EXPERIMENTAL

Drug: ACZ885

Interventions

ACZ885 DRUG

Cohort 1 - canakinumab dose reduction; Cohort 2 - canakinumab dose reduction

Canakinumab DRUG

Canakinumab - Cohort 1, 2mg; Canakinumab - Cohort 1, 4mg

Eligibility Criteria

• Age: 2 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Cohort 1:
• \. All patients currently enrolled in study CACZ885G2301E1, including patients who discontinued canakinumab therapy for inactive disease in CACZ885G2301E1 as per physician discretion and who are now currently in a flare and require canakinumab therapy again
• Cohort 2:
• Male and female patients aged ≥ 2 to \< 20 years at the time of the screening visit
• Confirmed diagnosis of SJIA as per ILAR definition that must have occurred at least 2 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:
• Evanescent non-fixed erythematous rash,
• Generalized lymph node enlargement,
• Hepatomegaly and/ or splenomegaly,
• Serositis
• Active systemic disease at the time of baseline visit 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 (using ACR definition of active joint),
• C-reactive protein (CRP) \> 30 mg/L (normal range \< 10 mg/L),
• Rash,

You may not qualify if:

• Cohort 1 and Cohort 2:
• Active or recurrent bacterial, fungal or viral infection at the time of enrollment
• 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 in an immunomodulatory therapy.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Live vaccinations within 3 months prior to the start of the study.
• Cohort 2:
• Presence of moderate to severe impaired renal function
• Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests at screening
• History/evidence of macrophage activation syndrome within the previous 6 months

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• PRINTO / PRCSG: collaborator

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2012
• First Posted: August 31, 2012
• Study Start: January 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: October 15, 2015

Record last verified: 2015-10