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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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ClinicalTrials.gov Identifier: NCT03780959
Recruitment Status : Completed
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 in children with polyarticular course JRA.

Condition or disease Intervention/treatment Phase
Juvenile Rheumatoid Arthritis Drug: Etanercept Drug: Placebo Phase 2 Phase 3

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).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 69 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Safety, Population Pharmacokinetics, and Efficacy of Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein (TNFR:Fc) in Children With Juvenile Rheumatoid Arthritis
Actual Study Start Date : May 1, 1997
Actual Primary Completion Date : July 8, 1998
Actual Study Completion Date : July 8, 1998


Arm Intervention/treatment
Placebo Comparator: Etanercept/Placebo
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.
Drug: Etanercept
Administered twice weekly by subcutaneous injection
Other Names:
  • Enbrel
  • TNFR:Fc

Drug: Placebo
Administered twice weekly by subcutaneous injection

Experimental: Etanercept/Etanercept
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.
Drug: Etanercept
Administered twice weekly by subcutaneous injection
Other Names:
  • Enbrel
  • TNFR:Fc




Primary Outcome Measures :
  1. Percentage of Participants With Disease Flare in Part 2 [ Time Frame: End of part 1 (day 90) and months 4 to 7 ]

    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 :
  1. Time to Flare in Part 2 [ Time Frame: Months 4 to 7 ]
    The time from day 90 to flare. Participants who withdrew without flare were censored at the time of withdrawal.

  2. 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). ]


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Ages Eligible for Study:   4 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03780959     History of Changes
Other Study ID Numbers: 20021616
016.0016 ( 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
Necrosis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Etanercept
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors