Safety and Efficacy Study of Etanercept (Enbrel®) In Children With Systemic Onset Juvenile Rheumatoid Arthritis

Study Overview
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Brief Summary
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The primary objective of this study was to determine the efficacy of etanercept in pediatric patients with systemically active system onset juvenile rheumatoid arthritis (SOJRA).

Detailed Description
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Participants were to receive etanercept at a dose of 0.4 mg/kg twice weekly in Part 1A. Participants who had a partial response (not able to reduce prednisone dose by 50% of the baseline dose in 5 months) while on 0.4 mg/kg twice weekly etanercept in Part 1A were to enter Part 1B for up to 4 months and were to have the dose of etanercept increased to 0.8 mg/kg twice weekly. Participants who did not meet the response criteria in Part 1A or Part 1B of the study were to be withdrawn from the study as non-responders. Participants who responded in either Part 1A or Part 1B were randomized into Part 2, where they received etanercept or matching placebo in a double-blind manner twice weekly for up to 3 months. In Part 2, participants were stratified by the dosage of etanercept (0.4 mg/kg or 0.8 mg/kg) they were receiving in Part 1A or Part 1B. Participants could enter Part 3, the open-label re-treatment portion of the study, only if they had been entered into Part 2 of the study and had either flared in Part 2 or had completed 3 months of treatment in Part 2. The maximum time participants could receive etanercept in Part 2 and Part 3 combined was 12 months.

Official Title
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A Phase 3 Safety and Efficacy Study of Etanercept In Children With Systemic Onset Juvenile Rheumatoid Arthritis

Conditions
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Juvenile Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Etanercept
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: 2 - 18 years of age SOJRA for at least 3 months, with stable systemic features If taking methotrexate, hydroxychloroquine, or NSAIDs, dose must be stable Must take prednisone at a stable dose EXCLUSION CRITERIA: Need for other DMARDs or prestudy requirements for oral or parenteral pulse steroids or intra-articular steroids Pregnant or nursing female Clinically significant abnormal laboratory test results for blood cells, liver or kidney function, or serology Previous receipt of any tumor necrosis factor (TNF) inhibitor Live virus vaccine within 12 weeks of study entry Participation in another study requiring informed consent within 12 weeks of entry Diabetes that requires insulin treatment Infection, chronic, recurrent, or currently active Any serious medical or psychiatric condition or history of alcohol or drug abuse

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Etanercept<br>Participants received 0.4 mg/kg etanercept administered subcutaneously twice a week for up to 6 months in Part 1A. Participants who had a partial response entered Part 1B and received 0.8 mg/kg etanercept twice weekly for up to 4 months. | Drug: Etanercept<br>* Administered by subcutaneous injection twice a week<br>* Other names: Enbrel;|
| Placebo Comparator: Part 2: Placebo<br>Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months. | Drug: Placebo<br>* Administered by subcutaneous injection twice a week<br>|
| Experimental: Part 2: Etanercept<br>Participants who met response criteria in Part 1 were randomized to continue receiving etanercept twice a week at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to 3 months. | Drug: Etanercept<br>* Administered by subcutaneous injection twice a week<br>* Other names: Enbrel;|
| Experimental: Part 3:<br>Participants who experienced a flare or completed 3 months of treatment in Part 2 entered Part 3 and received open-label treatment with etanercept at the same dose as in Part 1 (0.4 or 0.8 mg/kg) for up to a maximum of 12 months, including treatment in Part 2. | Drug: Etanercept<br>* Administered by subcutaneous injection twice a week<br>* Other names: Enbrel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants in Part 2 With Disease Flare | Disease flare was defined as the presence of: 1 major flare criterion plus 1 minor flare criterion or 1 lab criterion, OR 2 minor flare criteria plus 2 lab criteria Major Criteria: Fever of SOJRA, defined as a spike in axillary temperature ≥ 100°F (38°C) for ≥ 2 days per week in the prior 2 weeks or 8 days during the prior month Symptomatic serositis documented by x-ray or other imaging modality Minor Flare Criteria Rash of SOJRA, documented in the daily diary Splenomegaly defined as spleen palpable > 2 cm below the left costal margin Lymphadenopathy defined as ≥ 1 cm in > 1 node area Arthritis defined as ≥ 2 active joints with swelling not due to deformity, or if swelling is absent, then 2 joints with loss of motion with pain on passive motion and/or warmth. Laboratory Criteria: All labs should be outside the normal range and with 30% worsening: Albumin Platelet count Hemoglobin C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) | 3 months during Part 2 (depending on the timing of response, entry into Part 2 was between study months 3 and 10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events |  | Part 1A, maximum duration on treatment was 207 days; Part 1B, maximum duration on treatment was 120 days; Part 2, maximum duration on treatment was 88 days; Part 3, maximum duration on treatment was 130 days; plus 30 days after last dose of study drug. | 
| Time to Flare in Part 2 | Time to flare was defined as the time from first dose of etanercept in Part 1 to the date of flare during Part 2. | From first dose in Part 1 to the end of Part 2 (up to 13 months) | 
| Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 | Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms). | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | 
| Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 | Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms). | Baseline and months 5, 6, 7, 8, and 9 | 
| Change From Baseline in Patient's/Parent's Global Assessment in Part 1 | Patient's/parent's global assessment of overall well-being assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms). | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | 
| Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 | Patient's/parent's global assessment of overall well-being assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms). | Baseline and months 5, 6, 7, 8, and 9 | 
| Change From Baseline in Number of Active Joints in Part 1 | Active joints are those with swelling not due to bony deformity or if swelling is absent, loss of motion (LOM) accompanied by pain on passive motion and/or tenderness and/or warmth. | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | 
| Change From Baseline in Number of Active Joints in Part 2 | Active joints are those with swelling not due to bony deformity or if swelling is absent, loss of motion (LOM) accompanied by pain on passive motion and/or tenderness and/or warmth. | Baseline and months 5, 6, 7, 8, and 9 | 
| Change From Baseline in Number of Joints With Limitation of Motion in Part 1 |  | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | 
| Change From Baseline in Number of Joints With Limitation of Motion in Part 2 |  | Baseline and months 5, 6, 7, 8, and 9 | 
| Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1 | Childhood Health Assessment Questionnaire (CHAQ) disability index is used to assess physical functioning in children with arthritis. The scale consists of 30 questions in 8 domains (dressing, grooming, arising, eating, walking, reach, grip, and activities). Each question is scored on a scale from 0 to 3, where 0 = Without any difficulty; 1 = With some difficulty; 2 = With much difficulty; 3 = Unable to do. The overall score ranges from 0 (no difficulty) to 3 (unable to do). | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | 
| Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 | Childhood Health Assessment Questionnaire (CHAQ) disability index is used to assess physical functioning in children with arthritis. The scale consists of 30 questions in 8 domains (dressing, grooming, arising, eating, walking, reach, grip, and activities). Each question is scored on a scale from 0 to 3, where 0 = Without any difficulty; 1 = With some difficulty; 2 = With much difficulty; 3 = Unable to do. The overall score ranges from 0 (no difficulty) to 3 (unable to do). | Baseline and months 5, 6, 7, 8, and 9 | 
| Change From Baseline in C-reactive Protein (CRP) Levels in Part 1 |  | Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 | 
| Change From Baseline in C-reactive Protein (CRP) Levels in Part 2 |  | Baseline and months 5, 6, 7, 8, and 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Onset Juvenile Rheumatoid Arthritis, SOJRA, Fever, Rash, Joint Pain