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

Phase 2

Completed

Conditions: Juvenile Idiopathic Arthritis

Interventions: Biological: Rilonacept

Registration Number: NCT00534495

Lead Sponsor: Montefiore Medical Center

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 71

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	Rilonacept	Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study
Group 2	Rilonacept	Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study

Primary Outcome Measures

Name	Time	Method
Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS	At Weeks 0- 24
Time to Response to Treatment, as Determined by a Modified JIA ACR30 Requiring no Fever, Coupled With a Requirement for Corticosteroid Taper in Participants Who Are Taking Corticosteroids	At Week 12

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70	At Week 4 and week 12
Pediatric Quality of Life Inventory	At Weeks 4, 12 and 24	Visual Analog Score (0-100 mm) 0 very well , 100 very poor
Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ)	At Weeks 12 and 24	Childhood Health Assesment Questionairre dissability index (C-HAQ)-DI, Disability Index Calculation: The index is calculated by adding the scores for each of the categories and dividing by the number of categories answered. This gives a score in the 0 to 3.0 range. lower is better
Number of Participants With Presence of Systemic Features ( Fever, Rash)	At Weeks 4, 12 and 24