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

Randomized Placebo Phase Study of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis (RAPPORT)

Systemic juvenile idiopathic arthritis (SJIA) is a type of arthritis that typically occurs before 16 years of age. SJIA usually involves heat, pain, swelling, and stiffness in the body's joints. It can also involve fever, rash, anemia, and inflammation in various parts of the body. Rilonacept is a drug that can reduce inflammation. 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.

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