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Etanercept Plus Methotrexate Versus Methotrexate Alone in Children With Polyarticular Course Juvenile Rheumatoid Arthritis

Primary Purpose

Juvenile Rheumatoid Arthritis

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

About this trial

This is an interventional treatment trial for Juvenile Rheumatoid Arthritis

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)Does not accept healthy volunteers

Inclusion Criteria:

  • Patients must have had a diagnosis of JRA by the American College of Rheumatology (ACR) criteria. Disease onset may have been systemic, polyarticular, or pauciarticular
  • Disease course must have been polyarticular with at least 5 active joints
  • Duration of disease was not limited, but must have been long enough for the patient to have been given a 3-month trial of non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate at a dose between 0.3 and 1.0 mg/kg/week, orally (PO) or subcutaneously (SC)
  • Receiving methotrexate at a dose between 0.3 mg/kg/wk and 1 mg/kg/wk at time of randomization. The dose of methotrexate must have been stable for one month prior to entry
  • Patients may have failed prednisone, or been on a dosage of prednisone not to have exceeded 10 mg/day or 0.20 mg/kg/day (whichever was less)
  • At the time of qualification (screening) for study and prior to wash-out of all disease modifying anti-rheumatic drugs (DMARDs), the patient must have had active disease, defined as ≥ 5 swollen joints accompanied by pain, and/or tenderness and/or warmth, and ≥ 3 joints with limitation of motion (LOM). (The joints with LOM may have been the same as those with swelling)
  • Had good venous access and stable hematocrit ≥ 24 mL/dL
  • Patients must have been pre-pubescent, or if post-pubertal at anytime during the study, and of child-bearing potential, must have been practicing adequate contraception
  • Parent or legal guardian was able and willing to give informed consent
  • Parent or legal guardian must have been willing to actively supervise storage and administration of study drug and ensure that the date and time of each dose was accurately recorded in the subject's diary

Exclusion Criteria:

  • Was unable to meet the concurrent medication restrictions as described in the protocol
  • Pregnant or nursing female

  • Patients were excluded if they demonstrated clinically significant deviations from normal (as defined below) in any of the following laboratory parameters:

    • thrombocytopenia; platelet count < 100,000/cmm
    • leukopenia; total white cell count < 4000 cells/cmm
    • neutropenia; neutrophils < 1000 cells/cmm
    • hepatic transaminase levels > two times the upper limit of normal (ULN)
    • serum bilirubin > two times the ULN
    • estimated creatinine clearance of < 90 mL/min/1.73 M² body surface area (BSA)
    • known human immunodeficiency virus (HIV), hepatitis B surface antigen positivity not related to vaccination, or hepatitis C antibody positivity
  • Had received etanercept, antibody to tumor necrosis factor (TNF) (i.e. infliximab or D2E7), antibody to cluster of differentiation (CD)4 (anti-CD4), diphtheria interleukin (IL)-2 fusion protein (DAB-IL-2) or leflunomide
  • Had received DMARDs including D-penicillamine, hydroxychloroquine, sulfasalazine, oral or injectable gold, cyclosporin, azathioprine; intravenous immunoglobulin (IV Ig); or broadly immunosuppressant chemotherapeutic agents (e.g. cyclophosphamide, FK506, mycophenolate mofetil [CellCept]), for at least 28 days prior to enrollment and dosing of study drug. All DMARDs, other than methotrexate, must have been washed-out for a minimum of 28 days
  • Had received intraarticular glucocorticoid injection within 28 days prior to enrollment on study
  • Had previously received live virus vaccine within 3 months prior to study entry
  • Had participated in a study of an investigational drug or biologic requiring informed-consent within three months prior to study entry
  • Any concurrent medical condition which would have, in the investigator's opinion, compromised the patient's ability to tolerate the study drug or would have made the patient unable to cooperate with the protocol
  • History of/or current psychiatric illness that would have interfered with ability to comply with protocol requirements or give informed consent
  • Chronic or recurrent infections, or currently active infection at screening
  • History of alcohol or drug abuse that would have interfered with ability to comply with protocol requirements
  • Inability to have complied with the study requirements

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Experimental

    Arm Label

    Methotrexate + Placebo

    Methotrexate + Etanercept

    Arm Description

    Participants received placebo subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.

    Participants received 0.4 mg/kg etanercept subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants With a JRA Response at Month 6
    Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 30% improvement from baseline in at least three of the six JRA Core Set Criteria and ≥ 30% worsening in not more than one of the six assessments. The JRA Core Set Criteria consist of: Physician's global assessment of disease severity assessed on a visual analog scale (VAS) from 1 to 10 Patient's/Parent's global assessment of overall well being assessed on a VAS from 1 to 10 Number of active joints (swelling, not due to deformity, or if no swelling is present, limitation of motion accompanied by pain on passive motion and/or tenderness and/or warmth) Number of joints with limitation of motion Childhood Health Assessment Questionnaire (CHAQ) Erythrocyte sedimentation rate (ESR)

    Secondary Outcome Measures

    Percentage of Participants With a 50% Improvement in JRA DOI at Month 6
    Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 50% improvement from baseline in at least three of the six JRA Core Set Criteria and ≥ 30% worsening in not more than one of the six assessments. The JRA Core Set Criteria consist of: Physician's global assessment of disease severity assessed on a visual analog scale (VAS) from 1 to 10 Patient's/Parent's global assessment of overall well being assessed on a VAS from 1 to 10 Number of active joints (swelling, not due to deformity, or if no swelling is present, limitation of motion accompanied by pain on passive motion and/or tenderness and/or warmth) Number of joints with limitation of motion Childhood Health Assessment Questionnaire (CHAQ) Erythrocyte sedimentation rate (ESR)
    Percentage of Participants With a 70% Improvement in JRA DOI at Month 6
    Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 70% improvement from baseline in at least three of the six JRA Core Set Criteria and ≥ 30% worsening in not more than one of the six assessments. The JRA Core Set Criteria consist of: Physician's global assessment of disease severity assessed on a visual analog scale (VAS) from 1 to 10 Patient's/Parent's global assessment of overall well being assessed on a VAS from 1 to 10 Number of active joints (swelling, not due to deformity, or if no swelling is present, limitation of motion accompanied by pain on passive motion and/or tenderness and/or warmth) Number of joints with limitation of motion Childhood Health Assessment Questionnaire (CHAQ) Erythrocyte sedimentation rate (ESR)

    Full Information

    First Posted
    December 18, 2018
    Last Updated
    June 12, 2019
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03781375
    Brief Title
    Etanercept Plus Methotrexate Versus Methotrexate Alone in Children With Polyarticular Course Juvenile Rheumatoid Arthritis
    Official Title
    A Phase III Double Blind Randomized Study Comparing Etanercept (Enbrel) Combined With Methotrexate vs Methotrexate Alone in Children With Polyarticular Course Juvenile Rheumatoid Arthritis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2019
    Overall Recruitment Status
    Terminated
    Study Start Date
    August 24, 2000 (Actual)
    Primary Completion Date
    June 20, 2002 (Actual)
    Study Completion Date
    June 24, 2002 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The primary objective of this study was to determine the efficacy of etanercept plus methotrexate vs methotrexate alone in pediatric patients with active polyarticular course juvenile rheumatoid arthritis (JRA).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Juvenile Rheumatoid Arthritis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    25 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Methotrexate + Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants received placebo subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.
    Arm Title
    Methotrexate + Etanercept
    Arm Type
    Experimental
    Arm Description
    Participants received 0.4 mg/kg etanercept subcutaneous injections twice weekly and methotrexate once a week at the same dose as prior to study entry for 6 months. After month 6 participants received open-label 0.4 mg/kg etanercept twice weekly plus methotrexate for an additional 6 months.
    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 to Etanerceot
    Intervention Description
    Administered by subcutaneous injection twice a week
    Intervention Type
    Drug
    Intervention Name(s)
    Methotrexate
    Intervention Description
    Administered orally or subcutaneously once a week at the same dose as prior to study entry
    Primary Outcome Measure Information:
    Title
    Percentage of Participants With a JRA Response at Month 6
    Description
    Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 30% improvement from baseline in at least three of the six JRA Core Set Criteria and ≥ 30% worsening in not more than one of the six assessments. The JRA Core Set Criteria consist of: Physician's global assessment of disease severity assessed on a visual analog scale (VAS) from 1 to 10 Patient's/Parent's global assessment of overall well being assessed on a VAS from 1 to 10 Number of active joints (swelling, not due to deformity, or if no swelling is present, limitation of motion accompanied by pain on passive motion and/or tenderness and/or warmth) Number of joints with limitation of motion Childhood Health Assessment Questionnaire (CHAQ) Erythrocyte sedimentation rate (ESR)
    Time Frame
    Baseline and month 6
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With a 50% Improvement in JRA DOI at Month 6
    Description
    Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 50% improvement from baseline in at least three of the six JRA Core Set Criteria and ≥ 30% worsening in not more than one of the six assessments. The JRA Core Set Criteria consist of: Physician's global assessment of disease severity assessed on a visual analog scale (VAS) from 1 to 10 Patient's/Parent's global assessment of overall well being assessed on a VAS from 1 to 10 Number of active joints (swelling, not due to deformity, or if no swelling is present, limitation of motion accompanied by pain on passive motion and/or tenderness and/or warmth) Number of joints with limitation of motion Childhood Health Assessment Questionnaire (CHAQ) Erythrocyte sedimentation rate (ESR)
    Time Frame
    Baseline and month 6
    Title
    Percentage of Participants With a 70% Improvement in JRA DOI at Month 6
    Description
    Response was defined using the JRA definition of improvement (JRA DOI) as a ≥ 70% improvement from baseline in at least three of the six JRA Core Set Criteria and ≥ 30% worsening in not more than one of the six assessments. The JRA Core Set Criteria consist of: Physician's global assessment of disease severity assessed on a visual analog scale (VAS) from 1 to 10 Patient's/Parent's global assessment of overall well being assessed on a VAS from 1 to 10 Number of active joints (swelling, not due to deformity, or if no swelling is present, limitation of motion accompanied by pain on passive motion and/or tenderness and/or warmth) Number of joints with limitation of motion Childhood Health Assessment Questionnaire (CHAQ) Erythrocyte sedimentation rate (ESR)
    Time Frame
    Baseline and month 6

    10. Eligibility

    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients must have had a diagnosis of JRA by the American College of Rheumatology (ACR) criteria. Disease onset may have been systemic, polyarticular, or pauciarticular Disease course must have been polyarticular with at least 5 active joints Duration of disease was not limited, but must have been long enough for the patient to have been given a 3-month trial of non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate at a dose between 0.3 and 1.0 mg/kg/week, orally (PO) or subcutaneously (SC) Receiving methotrexate at a dose between 0.3 mg/kg/wk and 1 mg/kg/wk at time of randomization. The dose of methotrexate must have been stable for one month prior to entry Patients may have failed prednisone, or been on a dosage of prednisone not to have exceeded 10 mg/day or 0.20 mg/kg/day (whichever was less) At the time of qualification (screening) for study and prior to wash-out of all disease modifying anti-rheumatic drugs (DMARDs), the patient must have had active disease, defined as ≥ 5 swollen joints accompanied by pain, and/or tenderness and/or warmth, and ≥ 3 joints with limitation of motion (LOM). (The joints with LOM may have been the same as those with swelling) Had good venous access and stable hematocrit ≥ 24 mL/dL Patients must have been pre-pubescent, or if post-pubertal at anytime during the study, and of child-bearing potential, must have been practicing adequate contraception Parent or legal guardian was able and willing to give informed consent Parent or legal guardian must have been willing to actively supervise storage and administration of study drug and ensure that the date and time of each dose was accurately recorded in the subject's diary Exclusion Criteria: Was unable to meet the concurrent medication restrictions as described in the protocol Pregnant or nursing female Patients were excluded if they demonstrated clinically significant deviations from normal (as defined below) in any of the following laboratory parameters: thrombocytopenia; platelet count < 100,000/cmm leukopenia; total white cell count < 4000 cells/cmm neutropenia; neutrophils < 1000 cells/cmm hepatic transaminase levels > two times the upper limit of normal (ULN) serum bilirubin > two times the ULN estimated creatinine clearance of < 90 mL/min/1.73 M² body surface area (BSA) known human immunodeficiency virus (HIV), hepatitis B surface antigen positivity not related to vaccination, or hepatitis C antibody positivity Had received etanercept, antibody to tumor necrosis factor (TNF) (i.e. infliximab or D2E7), antibody to cluster of differentiation (CD)4 (anti-CD4), diphtheria interleukin (IL)-2 fusion protein (DAB-IL-2) or leflunomide Had received DMARDs including D-penicillamine, hydroxychloroquine, sulfasalazine, oral or injectable gold, cyclosporin, azathioprine; intravenous immunoglobulin (IV Ig); or broadly immunosuppressant chemotherapeutic agents (e.g. cyclophosphamide, FK506, mycophenolate mofetil [CellCept]), for at least 28 days prior to enrollment and dosing of study drug. All DMARDs, other than methotrexate, must have been washed-out for a minimum of 28 days Had received intraarticular glucocorticoid injection within 28 days prior to enrollment on study Had previously received live virus vaccine within 3 months prior to study entry Had participated in a study of an investigational drug or biologic requiring informed-consent within three months prior to study entry Any concurrent medical condition which would have, in the investigator's opinion, compromised the patient's ability to tolerate the study drug or would have made the patient unable to cooperate with the protocol History of/or current psychiatric illness that would have interfered with ability to comply with protocol requirements or give informed consent Chronic or recurrent infections, or currently active infection at screening History of alcohol or drug abuse that would have interfered with ability to comply with protocol requirements Inability to have complied with the study requirements
    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

    Learn more about this trial

    Etanercept Plus Methotrexate Versus Methotrexate Alone in Children With Polyarticular Course Juvenile Rheumatoid Arthritis

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