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

• ClinicalTrials.gov Identifier: NCT00534495
• Recruitment Status: Completed
• First Posted: September 26, 2007
• Results First Posted: December 11, 2015
• Last Update Posted: December 11, 2015
• Sponsor: Montefiore Medical Center
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Information provided by (Responsible Party): Norman Ilowite, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Juvenile Idiopathic Arthritis	Biological: Rilonacept	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 71 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Placebo Phase Study of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis (RAPPORT)
• Study Start Date: November 2008
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study	Biological: Rilonacept; 2.2 mg/kg subcutaneously; Other Names: IL-1 Trap; Arcalyst
Placebo Comparator: Group 2; 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	Biological: Rilonacept; 2.2 mg/kg subcutaneously; Other Names: IL-1 Trap; Arcalyst

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: At Week 12 ]
2. Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS [ Time Frame: At Weeks 0- 24 ]

Secondary Outcome Measures :

1. Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70 [ Time Frame: At Week 4 and week 12 ]
2. Pediatric Quality of Life Inventory [ Time Frame: At Weeks 4, 12 and 24 ]
   Visual Analog Score (0-100 mm) 0 very well , 100 very poor
3. Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) [ Time Frame: 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

4. Number of Participants With Presence of Systemic Features ( Fever, Rash) [ Time Frame: At Weeks 4, 12 and 24 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Months to 19 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

Sponsors and Collaborators

Montefiore Medical Center

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

• Principal Investigator: Norman T. Ilowite, MD; Montefiore Medical Center

More Information

• Responsible Party: Norman Ilowite, Chief, Division of Rheumatology, Children's Hospital at Montefiore, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• ClinicalTrials.gov Identifier: NCT00534495 History of Changes
• Other Study ID Numbers: N01 AR070015; 268200700015C-2-0-0 ( U.S. NIH Grant/Contract ); HHSN2682007000015C
• First Posted: September 26, 2007
• Results First Posted: December 11, 2015
• Last Update Posted: December 11, 2015
• Last Verified: November 2015

Keywords provided by Norman Ilowite, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Systemic Juvenile Idiopathic Arthritis; Juvenile Rheumatoid Arthritis; Systemic Juvenile Rheumatoid Arthritis

Additional relevant MeSH terms:

Arthritis; Arthritis, Juvenile; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Rilonacept; Anti-Inflammatory Agents