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

Primary Purpose

Juvenile Rheumatoid Arthritis

Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Etanercept
Placebo
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Juvenile Rheumatoid Arthritis focused on measuring Systemic Onset Juvenile Rheumatoid Arthritis, SOJRA, Fever, Rash, Joint Pain

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Placebo Comparator

    Experimental

    Experimental

    Arm Label

    Part 1: Etanercept

    Part 2: Placebo

    Part 2: Etanercept

    Part 3:

    Arm Description

    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.

    Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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)

    Secondary Outcome Measures

    Number of Participants With Adverse Events
    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.
    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).
    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).
    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).
    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).
    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.
    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.
    Change From Baseline in Number of Joints With Limitation of Motion in Part 1
    Change From Baseline in Number of Joints With Limitation of Motion in Part 2
    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).
    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).
    Change From Baseline in C-reactive Protein (CRP) Levels in Part 1
    Change From Baseline in C-reactive Protein (CRP) Levels in Part 2

    Full Information

    First Posted
    March 5, 2004
    Last Updated
    August 23, 2019
    Sponsor
    Amgen
    Collaborators
    Immunex Corporation
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00078806
    Brief Title
    Safety and Efficacy Study of Etanercept (Enbrel®) In Children With Systemic Onset Juvenile Rheumatoid Arthritis
    Official Title
    A Phase 3 Safety and Efficacy Study of Etanercept In Children With Systemic Onset Juvenile Rheumatoid Arthritis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2019
    Overall Recruitment Status
    Terminated
    Why Stopped
    the study was terminated because of slow enrollment
    Study Start Date
    June 4, 2001 (Actual)
    Primary Completion Date
    May 6, 2004 (Actual)
    Study Completion Date
    May 6, 2004 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen
    Collaborators
    Immunex Corporation

    4. Oversight

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Juvenile Rheumatoid Arthritis
    Keywords
    Systemic Onset Juvenile Rheumatoid Arthritis, SOJRA, Fever, Rash, Joint Pain

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    19 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Part 1: Etanercept
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Part 2: Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants who met response criteria in Part 1 were randomized to receive placebo twice a week for up to 3 months.
    Arm Title
    Part 2: Etanercept
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Part 3:
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Etanercept
    Other Intervention Name(s)
    Enbrel
    Intervention Description
    Administered by subcutaneous injection twice a week
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Administered by subcutaneous injection twice a week
    Primary Outcome Measure Information:
    Title
    Number of Participants in Part 2 With Disease Flare
    Description
    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)
    Time Frame
    3 months during Part 2 (depending on the timing of response, entry into Part 2 was between study months 3 and 10)
    Secondary Outcome Measure Information:
    Title
    Number of Participants With Adverse Events
    Time Frame
    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.
    Title
    Time to Flare in Part 2
    Description
    Time to flare was defined as the time from first dose of etanercept in Part 1 to the date of flare during Part 2.
    Time Frame
    From first dose in Part 1 to the end of Part 2 (up to 13 months)
    Title
    Change From Baseline in Physician Global Assessment of Disease Severity in Part 1
    Description
    Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
    Time Frame
    Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
    Title
    Change From Baseline in Physician Global Assessment of Disease Severity in Part 2
    Description
    Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
    Time Frame
    Baseline and months 5, 6, 7, 8, and 9
    Title
    Change From Baseline in Patient's/Parent's Global Assessment in Part 1
    Description
    Patient's/parent's global assessment of overall well-being assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
    Time Frame
    Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
    Title
    Change From Baseline in Patient's/Parent's Global Assessment of Disease Severity in Part 2
    Description
    Patient's/parent's global assessment of overall well-being assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms).
    Time Frame
    Baseline and months 5, 6, 7, 8, and 9
    Title
    Change From Baseline in Number of Active Joints in Part 1
    Description
    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.
    Time Frame
    Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
    Title
    Change From Baseline in Number of Active Joints in Part 2
    Description
    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.
    Time Frame
    Baseline and months 5, 6, 7, 8, and 9
    Title
    Change From Baseline in Number of Joints With Limitation of Motion in Part 1
    Time Frame
    Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
    Title
    Change From Baseline in Number of Joints With Limitation of Motion in Part 2
    Time Frame
    Baseline and months 5, 6, 7, 8, and 9
    Title
    Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 1
    Description
    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).
    Time Frame
    Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
    Title
    Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2
    Description
    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).
    Time Frame
    Baseline and months 5, 6, 7, 8, and 9
    Title
    Change From Baseline in C-reactive Protein (CRP) Levels in Part 1
    Time Frame
    Baseline and months 1, 2, 3, 4, 5, 6, 7, 8, and 9
    Title
    Change From Baseline in C-reactive Protein (CRP) Levels in Part 2
    Time Frame
    Baseline and months 5, 6, 7, 8, and 9

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    2 Years
    Maximum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website
    URL
    http://download.veritasmedicine.com/REGFILES/amgen/Amgen_results_disclaimer.pdf
    Description
    Notice regarding posted summaries of trial results
    URL
    http://download.veritasmedicine.com/REGFILES/amgen/08D_FDAMA_113_Posting_Summary_916_ENBREL_20021631.pdf
    Description
    To access clinical trial results information click on this link
    URL
    http://www.enbrel.com/
    Description
    FDA-approved Drug Labeling

    Learn more about this trial

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

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