Research Study Summary
Randomized Placebo Phase Study of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis (RAPPORT)
Purpose of the study: 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.
Protocol summary: 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.
- Fulfill International League against Rheumatism (ILAR) criteria for SJIA
- Age =18 months to <20 years
- Active disease as defined as >2 active joints
- Not receiving methotrexate, or if taking methotrexate the dose has remained stable for 4 weeks prior to the screening visit, or has been discontinued 4 weeks prior to the screening visit
- Never treated with biologics or, if previously treated with biologics, discontinued etanercept for >4 weeks and infliximab or adalimumab >8 weeks prior to the screening visit
- Not receiving corticosteroids, or if taking oral corticosteroids the dose has remained stable for 2 weeks prior to the screening visit at <2 mg/kg/d and no more than 60 mg/d
- Treatment in the past with anakinra, rilonacept or other biologic IL-1 inhibitor
- Treatment with other disease modifying anti-rheumatic drug (DMARD) including but not limited to azathioprine, sulfasalazine, cyclosporine, tacrolimus, tocilizumab and thalidomide within 4 weeks or rituximab for 6 months or cyclophosphomide for 3 months of the screening visit
- Treatment with intra-articular corticosteroids within 4 weeks of the screening visit
- Treatment with pulse IV methylprednisolone within 4 weeks of the screening visit
- Treatment with leflunomide without cholestyramine washout at the end of therapy
- Treatment with cyclophosphamide within 3 months of the screening visit
- Treatment with intravenous immunoglobulin within 4 weeks of the screening visit
- Renal insufficiency Creatinine >1.2 mg/dL
- AST or ALT > 2 times upper limit of normal
- Total bilirubin > 1.5 mg/dL
- Thrombocytopenia <150,000 , leukopenia <3,500, neutropenia <1,500
- Abnormal PT (INR >1.2) or PTT (greater then the upper limit of normal)
- Hypofibrinogenemia (less than the lower limit of normal)
- Positive PPD with no documented history of previous tuberculosis (TB) treatment
- Administration of live or attenuated vaccine within 1 month of the screening visit
- Evidence of current or chronic recurrent infection
- Evidence of significant other non-SJIA illness, which would interfere with ability to complete the study
- Psychological or cognitive difficulties interfering with ability to adhere to study regimen
- Current drug or alcohol abuse
- Anticipated poor compliance
- Participation in another clinical interventional study within 30 days of enrollment
- Major surgical procedure within 6 weeks of enrollment
- Pregnant, lactating, or has the potential to become pregnant and does not agree to use an effective contraceptive method
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