Safety and Efficacy Study of Etanercept (Enbrel®) In Children With Systemic Onset Juvenile Rheumatoid Arthritis
- Registration Number
- NCT00078806
- Lead Sponsor
- Amgen
- Brief Summary
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
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 Participants who did not meet the response criteria in Part 1A or Part 1B of the study were to be withdrawn from the study as non-responders.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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 19
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Etanercept Etanercept 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. Part 2: Placebo Placebo Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months. Part 2: Etanercept Etanercept 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. Part 3: Etanercept 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.
- Primary Outcome Measures
Name Time Method Number of Participants in Part 2 With Disease Flare 3 months during Part 2 (depending on the timing of response, entry into Part 2 was between study months 3 and 10) 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)
- Secondary Outcome Measures
Name Time Method Change From Baseline in C-reactive Protein (CRP) Levels in Part 2 Baseline and months 5, 6, 7, 8, and 9 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 From first dose in Part 1 to the end of Part 2 (up to 13 months) Time to flare was defined as the time from first dose of etanercept in Part 1 to the date of flare during Part 2.
Change From Baseline in Physician Global Assessment of Disease Severity in Part 1 Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
Change From Baseline in Physician Global Assessment of Disease Severity in Part 2 Baseline and months 5, 6, 7, 8, and 9 Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
Change From Baseline in Patient's/Parent's Global Assessment in Part 1 Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 Patient's/parent's global assessment of overall well-being assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2 Baseline and months 5, 6, 7, 8, and 9 Patient's/parent's global assessment of overall well-being assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
Change From Baseline in Number of Active Joints in Part 1 Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 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.
Change From Baseline in Number of Active Joints in Part 2 Baseline and months 5, 6, 7, 8, and 9 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.
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 Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9 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).
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 Baseline and months 5, 6, 7, 8, and 9 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).
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