Safety and Effectiveness of Rilonacept for Treating Systemic Juvenile Idiopathic Arthritis in Children and Young Adults

The current standard treatment for SJIA includes nonsteroidal anti-inflammatory drugs
(NSAIDS) and corticosteroids. However, in most people, NSAIDS do not completely control the
disease. Also, no studies have been done to prove which medication or combination of
medications is best to treat children and adolescents with SJIA. Interleukin-1 (IL-1), a
protein secreted by certain cells in the body, assists in regulating immune and inflammatory
responses. Too much IL-1 can be harmful and has been shown to play a role in the
inflammation associated with a variety of diseases, including SJIA. Rilonacept is a drug
that inhibits IL-1 activity. The purpose of this study is to determine whether a rilonacept
drug regimen initiated early is more effective than a similar rilonacept drug regimen
initiated 4 weeks later when treating children and young adults with SJIA. This study will
also evaluate the safety of rilonacept, and various tissue samples will be collected from
participants for future genetic studies.

This study will last 6 months. Participants will be randomly assigned to one of two groups:

- Group 1 participants will receive rilonacept injections at a dose of 4.4mg/kg at study
entry (loading dose), then 2.2 mg/kg weekly until Week 4. At Week 4, they will receive
a loading dose of placebo, followed by weekly rilonacept injections at 2.2 mg/kg for
the duration of the study.

- Group 2 participants will receive placebo at study entry and then during the first 4
weeks of treatment. At Week 4, they will receive a loading dose of rilonacept
injections of 4.4 mg/kg, followed by weekly rilonacept injections at a dose of 2.2
mg/kg for the duration of the study.

Participants will continue any previous corticosteroid therapy, but in tapering doses. All
participants will attend study visits at Weeks 0, 2, 4, 6, 8, 10, 12, 14 and 24. Study
visits will include a physical exam, joint exam, blood collection, interview, and
questionnaires. Urine collection may occur for some female participants. Other evaluations
may be performed by the participant's regular doctor. Throughout the study, participants
will maintain at-home diaries to record fever, morning stiffness and pain, when rilonacept
or placebo was taken, any side effects experienced from treatment, and any additional
medications that were taken.

Inclusion Criteria:

- Fulfills International League Against Rheumatism (ILAR) criteria for SJIA

- Duration of SJIA lasting at least 6 weeks since onset

- Active disease as defined by at least two joints with active disease

- Not currently receiving methotrexate OR if taking methotrexate, the dose has remained
stable or has been discontinued for 4 weeks prior to screening

- Has never received certain biologics OR if previously received biologics,
discontinued etanercept for at least 4 weeks prior to screening and discontinued
infliximab or adalimumab for at least 8 weeks prior to screening

- Not currently receiving corticosteroids OR if taking oral corticosteroids, the dose
has remained stable between 2 and 60 mg/day for at least 2 weeks prior to screening

Exclusion Criteria:

- Past treatment with anakinra, rilonacept, or other biologic IL-1 inhibitor

- Treatment with other disease-modifying antirheumatic drugs (DMARDs) including, but
not limited to, azathioprine, sulfasalazine, cyclosporine, and thalidomide within 4
weeks of screening

- Treatment with leflunomide without cholestyramine washout at the end of therapy

- Treatment with cyclophosphamide within 3 months of study entry

- Treatment with tacrolimus or tocilizumab within 4 weeks of study entry

- Treatment with rituximab within 6 months of study entry

- Treatment with intravenous immunoglobulin (IVIG) within 4 weeks of screening

- Kidney disease

- AST or ALT levels more than two times the upper limit of normal

- Bilirubin levels higher than 1.5 mg/dl

- Thrombocytopenia, leukopenia, or neutropenia

- Abnormal prothrombin time (PT) and partial thromboplastin time (PTT) tests

- Low levels of plasma fibrinogen

- Evidence of chronic recurrent infection or other significant, non-SJIA illness that
might interfere with study participation

- Psychological or cognitive difficulties that might interfere with study participation

- Current drug or alcohol abuse

- Anticipated poor compliance to assigned study regimen

- Participation in another clinical trial within 30 days of study entry

- Major surgical procedure within 3 months of study entry