Juvenile Idiopathic Arthritis
Conditions
Keywords
Systemic Juvenile Idiopathic Arthritis, Juvenile Rheumatoid Arthritis, Systemic Juvenile Rheumatoid Arthritis
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.
Interventions
BIOLOGICALRilonacept
2.2 mg/kg subcutaneously
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Months to 19 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | At Weeks 0- 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
United States
Participant flow
Pre-assignment details
71 participants enrolled. 1 participant was erroneously randomized and was not included in the analysis. This patient was not exposed to study drug
Participants by arm
| Arm | Count |
|---|---|
| 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
Rilonacept: 2.2 mg/kg subcutaneously | 36 |
| Placebo 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
Rilonacept: 2.2 mg/kg subcutaneously | 35 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| All Active Treatment Phase Week 4-24 | Adverse Event | 1 | 0 | 0 |
| All Active Treatment Phase Week 4-24 | Lack of Efficacy | 1 | 7 | 0 |
| All Active Treatment Phase Week 4-24 | Lost to Follow-up | 1 | 1 | 0 |
| All Active Treatment Phase Week 4-24 | Withdrawal by Subject | 1 | 1 | 0 |
| Double Blind Placebo Phase Week 0-4 | randomized in error | 0 | 1 | 0 |
| Long Term Ext. Phase Week 24-month 21 | Adverse Event | 0 | 0 | 1 |
| Long Term Ext. Phase Week 24-month 21 | Lack of Efficacy | 0 | 0 | 5 |
| Long Term Ext. Phase Week 24-month 21 | non compliance | 0 | 0 | 2 |
| Long Term Ext. Phase Week 24-month 21 | Withdrawal by Subject | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | Rilonacept | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 9.5 years STANDARD_DEVIATION 4.6 | 10 years STANDARD_DEVIATION 4.5 | 10.5 years STANDARD_DEVIATION 4.4 |
| Disease characteristics in the past Complete Macrophage Activation Syndrome | 1 participants | 2 participants | 1 participants |
| Disease characteristics in the past Incomplete Macrophage Activation Syndrome | 1 participants | 4 participants | 3 participants |
| Disease characteristics in the past Serositis | 9 participants | 17 participants | 8 participants |
| Disease characteristics in the past Systemic JIA rash | 32 participants | 65 participants | 33 participants |
| Disease Duration | 2.6 years STANDARD_DEVIATION 3.6 | 2.6 years STANDARD_DEVIATION 3.4 | 2.6 years STANDARD_DEVIATION 3.1 |
| No.of joints with active disease | 11.7 joints STANDARD_DEVIATION 9.6 | 11.1 joints STANDARD_DEVIATION 8.6 | 10.5 joints STANDARD_DEVIATION 7.6 |
| Prior medications Abatacept | 5 participants | 9 participants | 4 participants |
| Prior medications Anakinra | 13 participants | 26 participants | 13 participants |
| Prior medications Corticosteroids | 30 participants | 63 participants | 33 participants |
| Prior medications Etanercept | 12 participants | 28 participants | 16 participants |
| Prior medications Infliximab | 5 participants | 11 participants | 6 participants |
| Prior medications Leflunomide | 1 participants | 3 participants | 2 participants |
| Prior medications Methotrexate | 21 participants | 47 participants | 26 participants |
| Prior medications unknown Anakinra | 4 participants | 8 participants | 4 participants |
| Race/Ethnicity, Customized Black | 5 Participants | 12 Participants | 7 Participants |
| Race/Ethnicity, Customized Hispanic | 7 Participants | 12 Participants | 5 Participants |
| Race/Ethnicity, Customized Non-Hispanic | 29 Participants | 59 Participants | 30 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 11 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 48 Participants | 23 Participants |
| Sex: Female, Male Female | 23 Participants | 46 Participants | 23 Participants |
| Sex: Female, Male Male | 13 Participants | 25 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 36 | 19 / 35 | 27 / 35 | 28 / 33 | 28 / 40 |
| serious Total, serious adverse events | 1 / 36 | 1 / 35 | 3 / 35 | 1 / 33 | 6 / 40 |
Outcome results
Primary
Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS
Time frame: At Weeks 0- 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rilonacept | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | Serious Adverse Events | 4 events |
| Rilonacept | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | Adverse Events | 98 events |
| Rilonacept | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | Infections | 27 events |
| Rilonacept | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | MAS | 1 events |
| Placebo | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | MAS | 0 events |
| Placebo | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | Serious Adverse Events | 2 events |
| Placebo | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | Infections | 31 events |
| Placebo | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | Adverse Events | 186 events |
| Week 24- All Subjects | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | MAS | 0 events |
| Week 24- All Subjects | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | Adverse Events | 110 events |
| Week 24- All Subjects | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | Infections | 37 events |
| Week 24- All Subjects | Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS | Serious Adverse Events | 8 events |
Primary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rilonacept | 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 | 4 weeks |
| Placebo | 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 | 8 weeks |
Secondary
Number of Participants With Presence of Systemic Features ( Fever, Rash)
Time frame: At Weeks 4, 12 and 24
Population: At week 4 ,Rilonacept 36 and Placebo 34 participants , at week 12 , Rilonacept 33 and 29 Placebo participants , and at week 24 combined group with 57 participants, at baseline Rilonacept 36 and Placebo 35 participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rilonacept | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Fever at week12 | 4 participants |
| Rilonacept | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Fever at week 4 | 3 participants |
| Rilonacept | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Rash at week 12 | 3 participants |
| Rilonacept | Number of Participants With Presence of Systemic Features ( Fever, Rash) | beseline Rash | 15 participants |
| Rilonacept | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Rash at week 4 | 3 participants |
| Rilonacept | Number of Participants With Presence of Systemic Features ( Fever, Rash) | week 24 Fever | NA participants |
| Rilonacept | Number of Participants With Presence of Systemic Features ( Fever, Rash) | baseline Fever | 10 participants |
| Rilonacept | Number of Participants With Presence of Systemic Features ( Fever, Rash) | week 24 Rash | NA participants |
| Placebo | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Rash at week 4 | 8 participants |
| Placebo | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Fever at week 4 | 5 participants |
| Placebo | Number of Participants With Presence of Systemic Features ( Fever, Rash) | baseline Fever | 6 participants |
| Placebo | Number of Participants With Presence of Systemic Features ( Fever, Rash) | beseline Rash | 15 participants |
| Placebo | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Fever at week12 | 1 participants |
| Placebo | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Rash at week 12 | 1 participants |
| Placebo | Number of Participants With Presence of Systemic Features ( Fever, Rash) | week 24 Fever | NA participants |
| Placebo | Number of Participants With Presence of Systemic Features ( Fever, Rash) | week 24 Rash | NA participants |
| Week 24- All Subjects | Number of Participants With Presence of Systemic Features ( Fever, Rash) | beseline Rash | NA participants |
| Week 24- All Subjects | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Fever at week 4 | NA participants |
| Week 24- All Subjects | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Rash at week 4 | NA participants |
| Week 24- All Subjects | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Fever at week12 | NA participants |
| Week 24- All Subjects | Number of Participants With Presence of Systemic Features ( Fever, Rash) | Rash at week 12 | NA participants |
| Week 24- All Subjects | Number of Participants With Presence of Systemic Features ( Fever, Rash) | week 24 Fever | NA participants |
| Week 24- All Subjects | Number of Participants With Presence of Systemic Features ( Fever, Rash) | week 24 Rash | 4 participants |
| Week 24- All Subjects | Number of Participants With Presence of Systemic Features ( Fever, Rash) | baseline Fever | NA participants |
Secondary
Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70
Time frame: At Week 4 and week 12
Population: Participants in the study at week 4 (rilonacept 35 and placebo 33).Participants in the study at week 12 ( Rilonacept 33 and placebo 29).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rilonacept | Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70 | week 4 ,ACR 50 | 21 participants |
| Rilonacept | Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70 | week 12, ACR 50 | 26 participants |
| Rilonacept | Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70 | week 4 ,ACR 70 | 21 participants |
| Rilonacept | Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70 | week 12,ACR 70 | 28 participants |
| Placebo | Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70 | week 12,ACR 70 | 19 participants |
| Placebo | Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70 | week 4 ,ACR 50 | 10 participants |
| Placebo | Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70 | week 4 ,ACR 70 | 10 participants |
| Placebo | Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70 | week 12, ACR 50 | 13 participants |
Secondary
Pediatric Quality of Life Inventory
Visual Analog Score (0-100 mm) 0 very well , 100 very poor
Time frame: At Weeks 4, 12 and 24
Population: At Week 4 ,36 Rilonacept and 34 Placebo patient. At week 12, Rilonacept 33 patients and Placebo 29.At baseline Rilonacept 36 and Placebo 35 participants.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rilonacept | Pediatric Quality of Life Inventory | week 4 | 12 units on a scale |
| Rilonacept | Pediatric Quality of Life Inventory | week 12 | 3.5 units on a scale |
| Rilonacept | Pediatric Quality of Life Inventory | week 24 | NA units on a scale |
| Rilonacept | Pediatric Quality of Life Inventory | baseline | 49.5 units on a scale |
| Placebo | Pediatric Quality of Life Inventory | baseline | 53.0 units on a scale |
| Placebo | Pediatric Quality of Life Inventory | week 4 | 34 units on a scale |
| Placebo | Pediatric Quality of Life Inventory | week 24 | NA units on a scale |
| Placebo | Pediatric Quality of Life Inventory | week 12 | 8 units on a scale |
| Week 24- All Subjects | Pediatric Quality of Life Inventory | baseline | NA units on a scale |
| Week 24- All Subjects | Pediatric Quality of Life Inventory | week 12 | NA units on a scale |
| Week 24- All Subjects | Pediatric Quality of Life Inventory | week 24 | 7 units on a scale |
| Week 24- All Subjects | Pediatric Quality of Life Inventory | week 4 | NA units on a scale |
Secondary
Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ)
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
Time frame: At Weeks 12 and 24
Population: 36 Rilonacept and 35 placebo at baseline , 36 Rilonacept and 34 placebo at week 4, 33 Rilonacept and 29 placebo at week 12, and 57 combined at week 24.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rilonacept | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | week 4 | 0.43 units on a scale |
| Rilonacept | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | week 12 | 0.25 units on a scale |
| Rilonacept | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | week 24 | NA units on a scale |
| Rilonacept | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | baseline | 1.00 units on a scale |
| Placebo | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | baseline | 1.25 units on a scale |
| Placebo | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | week 4 | 0.88 units on a scale |
| Placebo | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | week 24 | NA units on a scale |
| Placebo | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | week 12 | 0.25 units on a scale |
| Week 24- All Subjects | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | baseline | NA units on a scale |
| Week 24- All Subjects | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | week 12 | NA units on a scale |
| Week 24- All Subjects | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | week 24 | 0.13 units on a scale |
| Week 24- All Subjects | Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) | week 4 | NA units on a scale |