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

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ClinicalTrials.gov Identifier: NCT03781375
Recruitment Status : Terminated
First Posted : December 19, 2018
Results First Posted : August 2, 2019
Last Update Posted : August 2, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

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).

Condition or disease Intervention/treatment Phase
Juvenile Rheumatoid Arthritis Drug: Etanercept Drug: Placebo to Etanerceot Drug: Methotrexate Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : August 24, 2000
Actual Primary Completion Date : June 20, 2002
Actual Study Completion Date : June 24, 2002


Arm Intervention/treatment
Placebo Comparator: Methotrexate + Placebo
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.
Drug: Etanercept
Administered by subcutaneous injection twice a week
Other Name: Enbrel

Drug: Placebo to Etanerceot
Administered by subcutaneous injection twice a week

Drug: Methotrexate
Administered orally or subcutaneously once a week at the same dose as prior to study entry

Experimental: Methotrexate + Etanercept
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.
Drug: Etanercept
Administered by subcutaneous injection twice a week
Other Name: Enbrel

Drug: Methotrexate
Administered orally or subcutaneously once a week at the same dose as prior to study entry




Primary Outcome Measures :
  1. Percentage of Participants With a JRA Response at Month 6 [ Time Frame: Baseline and 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 :
  1. Percentage of Participants With a 50% Improvement in JRA DOI at Month 6 [ Time Frame: Baseline and 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)

  2. Percentage of Participants With a 70% Improvement in JRA DOI at Month 6 [ Time Frame: Baseline and 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)



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03781375


Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03781375     History of Changes
Other Study ID Numbers: 20021628
016.0028 ( Other Identifier: Immunex Corporation )
First Posted: December 19, 2018    Key Record Dates
Results First Posted: August 2, 2019
Last Update Posted: August 2, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Etanercept
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents