A Multi-Center, Open label, Repeated Dose Range Finding Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics and Efficacy of an Anti-IL-1β Monoclonal Antibody (ACZ885) Given Subcutaneously in Pediatric Subjects with Active Systemic Juvenile Idiopathic Arthritis (SJIA)

- Male and female subjects aged 4 to 20 years at the time of the screening visit, having passed screening examinations. Parents* or legal guardian*s written informed consent (patient*s informed consent for >= 18 years of age) and child*s assent, if appropriate, are required prior to study participation.
- Female subjects of child-bearing potential may participate if they have a negative serum pregnancy test at screening and prior to dosing, and are willing to practice double-barrier contraception during the study (from the date of screening) and for at least 3 months following the last dose.
- Patient meets the diagnostic criteria for SJIA, has at least 6 months disease duration and has active disease defined at the time of enrollment defined as follows: At least 2 joints with active arthritis (using ACR definition of active joint) / spiking, intermittent fever (body temperature > 38.9°C only for several hours during the day) / CRP > 50 mg/L (normal range < 10 mg/L).
- Anakinra naïve, annakinra failure or willing to discontinue anakinra under close monitoring (run in phase) until relapse (reappearance of fever and/or CRP increase).
- Willing to discontinue second line agent such as disease-modifying and immunosuppressive drugs, not including methotrexate and corticosteroids.
- If part of the treatment at screening visit: Stable dose of methotrexate (maximum of 15 mg/m2/week) for at least eight weeks prior to the screening visit, and folic/folinic acid supplementation (according to standard medical practice of the center). Stable dose of no more than one NSAID for at least four weeks prior to the screening visit. Stable dose of oral prednisone (<= 0.4 mg/kg/day or <= 20 mg/day, whichever is lower) for at least one week prior to the screening visit.
- Body weight of at least 12 kg.
- Negative tuberculin skin test reaction (PPD 5 TU) (< 5 mm induration) at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines. Patients who have a positive PPD skin test with a documentation of BCG vaccination, who are at low environmental risk for tuberculosis infection or reactivation, and have a negative chest X-ray can be included A positive PPD sample will be defined using the MMWR 2000 guidance, summarized as criteria for tuberculin positivity by risk group.

- Etanercept in the four weeks prior to the Baseline visit.
- Adalimumab in the eight weeks prior to the Baseline visit.
- Infliximab in the eight weeks prior to the Baseline visit.
- Any other investigational biologics in the eight weeks prior to the Baseline visit.
- Leflunomide in the four weeks prior to the Baseline visit. Documentation of a completion of a full cholestyramine elimination procedure after most recent leflunomide use will be required.
- Thalidomide, Growth hormone , Cyclosporine, in the four weeks prior to the Baseline visit.
- Sulfasalazine or hydroxychloroquine in the eight weeks prior to the Baseline visit.
- i.v. immunoglobulin (i.v. Ig) in the eight weeks prior to the Baseline visit.
- 6-Merceptopurine, azathioprine, cyclophosphamide, or chlorambucil, in the 24 weeks prior to the Baseline visit.
- History of recurrent bacterial, fungal or viral infection.
- Evidence of currently active bacterial, fungal or viral infection.
- Administration of live attenuated vaccine.
- Uncontrolled severe systemic symptoms and/or biologic features of Macrophage Activation Syndrome (hemorrhages, central nervous system dysfunction, hepatomegaly, serum fibrinogen level < 2.5 g/L, cytopenia, hypertriglyceridemia, decreased platelet count, increased aspartate transaminase, hyperferritinemia).
- Familial and social conditions rendering regular medical assessment not possible.