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Safety and Efficacy of Etanercept (Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein [TNFR:Fc]) in Children With Juvenile Rheumatoid Arthritis (JRA)

Primary Purpose

Juvenile Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
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

Eligibility Criteria

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

Inclusion Criteria:

  • Diagnosis of JRA by the American College of Rheumatology (ACR) criteria.
  • Disease course must be polyarticular with disease duration long enough to have been given an adequate trial of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose methotrexate at a dose of at least 10 mg/m²/week
  • Continuing active disease, defined as ≥ 5 swollen joints and ≥ 3 joints with limitation of motion accompanied by pain, tenderness or warmth.
  • Disease refractory to methotrexate or intolerant of methotrexate.
  • Have not received disease-modifying anti-rheumatic drugs (DMARDs) within 28 days prior to enrollment.
  • Have not received methotrexate within 14 days prior to dosing of study drug.

Exclusion Criteria:

  • Pregnant or nursing female
  • Functional class IV by ACR criteria
  • Unable to meet concomitant medication restrictions
  • Intraarticular corticosteroid injection within 4 weeks prior to enrollment
  • Clinically significant deviations from normal, defined as:

    • 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 > 2 times ULN
    • creatinine clearance < 90 mL/min/1.73 m² body surface area (BSA) and/or a glomerular filtration rate (GFR) < 90 mL/min/1.73 m² BSA.
    • known human immunodeficiency virus (HIV), hepatitis B surface antigen positivity, or hepatitis C positivity.
    • anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies or anti-cardiolipin antibodies present.
  • Previously received antibody to TNF, antibody to cluster of differentiation (CD)4, or diphtheria interleukin (IL)-2-fusion protein (DAB-IL-2)
  • Participated in a study of an investigational drug or biologic requiring informed consent within 3 months prior to study entry.
  • Any concurrent medical condition which would, in the investigator's opinion, compromise the patient's ability to tolerate the study drug or make the patient unable to cooperate with the protocol.
  • History of or current psychiatric illness that would interfere with ability to comply with protocol requirements or informed consent.
  • History or drug or alcohol abuse that would interfere with ability to comply with protocol requirements

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Experimental

    Arm Label

    Etanercept/Placebo

    Etanercept/Etanercept

    Arm Description

    Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1. In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.

    Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1. In Part 2 participants were randomized to continue receiving etanercept twice weekly for up to 4 additional months.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants With Disease Flare in Part 2
    Disease flare was defined as a 30% or greater worsening in three of the six JRA Core Set Criteria and ≥ 30% improvement in one or less of the six JRA Core Set Criteria compared to day 90 and a minimum of two active joints (joints with swelling or limitation of movement plus pain and/or tenderness). The JRA Core Set criteria consisted of: Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms); Patient/parent global assessment of overall well-being assesses on a VAS from 0 (asymptomatic) to 10 (severe symptoms); Number of active joints; Number of joints with limitation of motion (LOM) and with pain, tenderness, or both; Childhood Health Assessment Questionnaire (CHAQ) disability domain; Erythrocyte sedimentation rate (ESR).

    Secondary Outcome Measures

    Time to Flare in Part 2
    The time from day 90 to flare. Participants who withdrew without flare were censored at the time of withdrawal.
    Number of Participants With Adverse Events

    Full Information

    First Posted
    December 18, 2018
    Last Updated
    June 10, 2019
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03780959
    Brief Title
    Safety and Efficacy of Etanercept (Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein [TNFR:Fc]) in Children With Juvenile Rheumatoid Arthritis (JRA)
    Official Title
    Safety, Population Pharmacokinetics, and Efficacy of Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein (TNFR:Fc) in Children With Juvenile Rheumatoid Arthritis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    May 1, 1997 (Actual)
    Primary Completion Date
    July 8, 1998 (Actual)
    Study Completion Date
    July 8, 1998 (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 in children with polyarticular course JRA.
    Detailed Description
    This was a two-part study. In the first part of the study, all participants received open-label etanercept twice a week for 90 days. At the end of the 90 days, participants with disease response as defined by the JRA Definition of Improvement (DOI) using the JRA Core Set Criteria were randomized in part 2 of the study to receive placebo or continued administration of etanercept until either disease flare occurred or 4 months elapsed, whichever was earlier. Participants who did not meet the DOI at day 90, participants who had disease flare during part 2 and participants who completed the blinded part of the study were eligible to receive open-label treatment with etanercept under protocol 16.0018 (NCT00357903).

    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 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    69 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Etanercept/Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1. In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.
    Arm Title
    Etanercept/Etanercept
    Arm Type
    Experimental
    Arm Description
    Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1. In Part 2 participants were randomized to continue receiving etanercept twice weekly for up to 4 additional months.
    Intervention Type
    Drug
    Intervention Name(s)
    Etanercept
    Other Intervention Name(s)
    Enbrel, TNFR:Fc
    Intervention Description
    Administered twice weekly by subcutaneous injection
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Administered twice weekly by subcutaneous injection
    Primary Outcome Measure Information:
    Title
    Percentage of Participants With Disease Flare in Part 2
    Description
    Disease flare was defined as a 30% or greater worsening in three of the six JRA Core Set Criteria and ≥ 30% improvement in one or less of the six JRA Core Set Criteria compared to day 90 and a minimum of two active joints (joints with swelling or limitation of movement plus pain and/or tenderness). The JRA Core Set criteria consisted of: Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms); Patient/parent global assessment of overall well-being assesses on a VAS from 0 (asymptomatic) to 10 (severe symptoms); Number of active joints; Number of joints with limitation of motion (LOM) and with pain, tenderness, or both; Childhood Health Assessment Questionnaire (CHAQ) disability domain; Erythrocyte sedimentation rate (ESR).
    Time Frame
    End of part 1 (day 90) and months 4 to 7
    Secondary Outcome Measure Information:
    Title
    Time to Flare in Part 2
    Description
    The time from day 90 to flare. Participants who withdrew without flare were censored at the time of withdrawal.
    Time Frame
    Months 4 to 7
    Title
    Number of Participants With Adverse Events
    Time Frame
    Part 1: 90 days (months 1-3) plus 30 days for participants who were not randomized into part 2. Part 2: From first dose of randomized treatment to 30 days after last dose (150 days; months 4-8).

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    4 Years
    Maximum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Diagnosis of JRA by the American College of Rheumatology (ACR) criteria. Disease course must be polyarticular with disease duration long enough to have been given an adequate trial of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose methotrexate at a dose of at least 10 mg/m²/week Continuing active disease, defined as ≥ 5 swollen joints and ≥ 3 joints with limitation of motion accompanied by pain, tenderness or warmth. Disease refractory to methotrexate or intolerant of methotrexate. Have not received disease-modifying anti-rheumatic drugs (DMARDs) within 28 days prior to enrollment. Have not received methotrexate within 14 days prior to dosing of study drug. Exclusion Criteria: Pregnant or nursing female Functional class IV by ACR criteria Unable to meet concomitant medication restrictions Intraarticular corticosteroid injection within 4 weeks prior to enrollment Clinically significant deviations from normal, defined as: 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 > 2 times ULN creatinine clearance < 90 mL/min/1.73 m² body surface area (BSA) and/or a glomerular filtration rate (GFR) < 90 mL/min/1.73 m² BSA. known human immunodeficiency virus (HIV), hepatitis B surface antigen positivity, or hepatitis C positivity. anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies or anti-cardiolipin antibodies present. Previously received antibody to TNF, antibody to cluster of differentiation (CD)4, or diphtheria interleukin (IL)-2-fusion protein (DAB-IL-2) Participated in a study of an investigational drug or biologic requiring informed consent within 3 months prior to study entry. Any concurrent medical condition which would, in the investigator's opinion, compromise the patient's ability to tolerate the study drug or make the patient unable to cooperate with the protocol. History of or current psychiatric illness that would interfere with ability to comply with protocol requirements or informed consent. History or drug or alcohol abuse that would interfere with ability to comply with protocol requirements

    12. IPD Sharing Statement

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    Safety and Efficacy of Etanercept (Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein [TNFR:Fc]) in Children With Juvenile Rheumatoid Arthritis (JRA)

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