<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03780959</url>
  </required_header>
  <id_info>
    <org_study_id>20021616</org_study_id>
    <secondary_id>016.0016</secondary_id>
    <nct_id>NCT03780959</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Etanercept (Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein [TNFR:Fc]) in Children With Juvenile Rheumatoid Arthritis (JRA)</brief_title>
  <official_title>Safety, Population Pharmacokinetics, and Efficacy of Recombinant Human Tumor Necrosis Factor Receptor Fusion Protein (TNFR:Fc) in Children With Juvenile Rheumatoid Arthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amgen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study was to determine the efficacy of etanercept in children&#xD;
      with polyarticular course JRA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a two-part study. In the first part of the study, all participants received&#xD;
      open-label etanercept twice a week for 90 days. At the end of the 90 days, participants with&#xD;
      disease response as defined by the JRA Definition of Improvement (DOI) using the JRA Core Set&#xD;
      Criteria were randomized in part 2 of the study to receive placebo or continued&#xD;
      administration of etanercept until either disease flare occurred or 4 months elapsed,&#xD;
      whichever was earlier.&#xD;
&#xD;
      Participants who did not meet the DOI at day 90, participants who had disease flare during&#xD;
      part 2 and participants who completed the blinded part of the study were eligible to receive&#xD;
      open-label treatment with etanercept under protocol 16.0018 (NCT00357903).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 1997</start_date>
  <completion_date type="Actual">July 8, 1998</completion_date>
  <primary_completion_date type="Actual">July 8, 1998</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Disease Flare in Part 2</measure>
    <time_frame>End of part 1 (day 90) and months 4 to 7</time_frame>
    <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).&#xD;
The JRA Core Set criteria consisted of:&#xD;
Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms);&#xD;
Patient/parent global assessment of overall well-being assesses on a VAS from 0 (asymptomatic) to 10 (severe symptoms);&#xD;
Number of active joints;&#xD;
Number of joints with limitation of motion (LOM) and with pain, tenderness, or both;&#xD;
Childhood Health Assessment Questionnaire (CHAQ) disability domain;&#xD;
Erythrocyte sedimentation rate (ESR).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Flare in Part 2</measure>
    <time_frame>Months 4 to 7</time_frame>
    <description>The time from day 90 to flare. Participants who withdrew without flare were censored at the time of withdrawal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <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).</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">69</enrollment>
  <condition>Juvenile Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Etanercept/Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Etanercept/Etanercept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etanercept</intervention_name>
    <description>Administered twice weekly by subcutaneous injection</description>
    <arm_group_label>Etanercept/Etanercept</arm_group_label>
    <arm_group_label>Etanercept/Placebo</arm_group_label>
    <other_name>Enbrel</other_name>
    <other_name>TNFR:Fc</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administered twice weekly by subcutaneous injection</description>
    <arm_group_label>Etanercept/Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of JRA by the American College of Rheumatology (ACR) criteria.&#xD;
&#xD;
          -  Disease course must be polyarticular with disease duration long enough to have been&#xD;
             given an adequate trial of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose&#xD;
             methotrexate at a dose of at least 10 mg/m²/week&#xD;
&#xD;
          -  Continuing active disease, defined as ≥ 5 swollen joints and ≥ 3 joints with&#xD;
             limitation of motion accompanied by pain, tenderness or warmth.&#xD;
&#xD;
          -  Disease refractory to methotrexate or intolerant of methotrexate.&#xD;
&#xD;
          -  Have not received disease-modifying anti-rheumatic drugs (DMARDs) within 28 days prior&#xD;
             to enrollment.&#xD;
&#xD;
          -  Have not received methotrexate within 14 days prior to dosing of study drug.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or nursing female&#xD;
&#xD;
          -  Functional class IV by ACR criteria&#xD;
&#xD;
          -  Unable to meet concomitant medication restrictions&#xD;
&#xD;
          -  Intraarticular corticosteroid injection within 4 weeks prior to enrollment&#xD;
&#xD;
          -  Clinically significant deviations from normal, defined as:&#xD;
&#xD;
               -  thrombocytopenia; platelet count &lt; 100,000/cmm&#xD;
&#xD;
               -  leukopenia; total white cell count &lt; 4000 cells/cmm&#xD;
&#xD;
               -  neutropenia; neutrophils &lt; 1000 cells/cmm&#xD;
&#xD;
               -  hepatic transaminase levels &gt; two times the upper limit of normal (ULN)&#xD;
&#xD;
               -  serum bilirubin &gt; 2 times ULN&#xD;
&#xD;
               -  creatinine clearance &lt; 90 mL/min/1.73 m² body surface area (BSA) and/or a&#xD;
                  glomerular filtration rate (GFR) &lt; 90 mL/min/1.73 m² BSA.&#xD;
&#xD;
               -  known human immunodeficiency virus (HIV), hepatitis B surface antigen positivity,&#xD;
                  or hepatitis C positivity.&#xD;
&#xD;
               -  anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies or anti-cardiolipin&#xD;
                  antibodies present.&#xD;
&#xD;
          -  Previously received antibody to TNF, antibody to cluster of differentiation (CD)4, or&#xD;
             diphtheria interleukin (IL)-2-fusion protein (DAB-IL-2)&#xD;
&#xD;
          -  Participated in a study of an investigational drug or biologic requiring informed&#xD;
             consent within 3 months prior to study entry.&#xD;
&#xD;
          -  Any concurrent medical condition which would, in the investigator's opinion,&#xD;
             compromise the patient's ability to tolerate the study drug or make the patient unable&#xD;
             to cooperate with the protocol.&#xD;
&#xD;
          -  History of or current psychiatric illness that would interfere with ability to comply&#xD;
             with protocol requirements or informed consent.&#xD;
&#xD;
          -  History or drug or alcohol abuse that would interfere with ability to comply with&#xD;
             protocol requirements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <results_first_submitted>June 10, 2019</results_first_submitted>
  <results_first_submitted_qc>June 10, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 2, 2019</results_first_posted>
  <last_update_submitted>June 10, 2019</last_update_submitted>
  <last_update_submitted_qc>June 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
    <mesh_term>Arthritis, Juvenile</mesh_term>
    <mesh_term>Necrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Etanercept</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at 9 sites in the United States and Canada. The study consisted of an open-label treatment period (part 1) where all participants received 0.4 mg etanercept twice weekly for 3 months, followed by a randomized double-blind treatment period (part 2).</recruitment_details>
      <pre_assignment_details>At the end of part 1 participants with disease response were randomized to part 2, with stratification according to study center and number of active joints (≤ 2 vs. &gt; 2) at the end of month 3.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part 1: Etanercept 0.4 mg/kg</title>
          <description>Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1.</description>
        </group>
        <group group_id="P2">
          <title>Part 2: Placebo</title>
          <description>In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.</description>
        </group>
        <group group_id="P3">
          <title>Part 2: Etanercept 0.4 mg/kg</title>
          <description>In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="69"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="64"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Parent/Guardian</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Response Status</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="26"/>
                <participants group_id="P3" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="19"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Parent/Guardian</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Response Status</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="18"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline data are included for all enrolled participants in part 1 (69) and all participants who randomized in part 2 (51).</population>
      <group_list>
        <group group_id="B1">
          <title>Part 1: Etanercept 0.4 mg/kg</title>
          <description>Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1.</description>
        </group>
        <group group_id="B2">
          <title>Part 2: Placebo</title>
          <description>In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.</description>
        </group>
        <group group_id="B3">
          <title>Part 2: Etanercept 0.4 mg/kg</title>
          <description>In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="69"/>
            <count group_id="B2" value="26"/>
            <count group_id="B3" value="25"/>
            <count group_id="B4" value="120"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Part 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="69"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="69"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.5" spread="3.9"/>
                    <measurement group_id="B4" value="10.5" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="26"/>
                    <count group_id="B3" value="25"/>
                    <count group_id="B4" value="51"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B2" value="12.2" spread="3.5"/>
                    <measurement group_id="B3" value="8.9" spread="3.7"/>
                    <measurement group_id="B4" value="10.6" spread="3.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <population>Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Part 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="69"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="69"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>4 - 8 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B4" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>9 - 12 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>13 - 17 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B4" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="26"/>
                    <count group_id="B3" value="25"/>
                    <count group_id="B4" value="51"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>4 - 8 years</title>
                  <measurement_list>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>9 - 12 years</title>
                  <measurement_list>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>13 - 17 years</title>
                  <measurement_list>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Part 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="69"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="69"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                    <measurement group_id="B4" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B4" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="26"/>
                    <count group_id="B3" value="25"/>
                    <count group_id="B4" value="51"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <population>Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Part 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="69"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="69"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B4" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hispanic</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="26"/>
                    <count group_id="B3" value="25"/>
                    <count group_id="B4" value="51"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hispanic</title>
                  <measurement_list>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native American</title>
                  <measurement_list>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Type of Onset of Juvenile Rheumatoid Arthritis (JRA)</title>
          <description>Onset type is determined by manifestations during the first 6 months of disease.&#xD;
Pauciarticular JRA: Arthritis in 4 or fewer joints during the first 6 months of disease.&#xD;
Polyarticular JRA: Arthritis in 5 or more joints during the first 6 months of disease.&#xD;
Systemic onset JRA: Arthritis with persistent intermittent fever with or without rheumatoid rash or other organ involvement.</description>
          <population>Part 1 and Part 2 baseline data are reported separately since Part 2 participants represent a subset of Part 1.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Part 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="69"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="69"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Pauciarticular</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Polyarticular</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B4" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Systemic</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B4" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Part 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="26"/>
                    <count group_id="B3" value="25"/>
                    <count group_id="B4" value="51"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Pauciarticular</title>
                  <measurement_list>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Polyarticular</title>
                  <measurement_list>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Systemic</title>
                  <measurement_list>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Disease Flare in Part 2</title>
        <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).&#xD;
The JRA Core Set criteria consisted of:&#xD;
Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms);&#xD;
Patient/parent global assessment of overall well-being assesses on a VAS from 0 (asymptomatic) to 10 (severe symptoms);&#xD;
Number of active joints;&#xD;
Number of joints with limitation of motion (LOM) and with pain, tenderness, or both;&#xD;
Childhood Health Assessment Questionnaire (CHAQ) disability domain;&#xD;
Erythrocyte sedimentation rate (ESR).</description>
        <time_frame>End of part 1 (day 90) and months 4 to 7</time_frame>
        <population>All randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Placebo</title>
            <description>In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Etanercept 0.4 mg/kg</title>
            <description>In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Disease Flare in Part 2</title>
          <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).&#xD;
The JRA Core Set criteria consisted of:&#xD;
Physician global assessment of disease severity assessed on a visual analog scale (VAS) from 0 (asymptomatic) to 10 (severe symptoms);&#xD;
Patient/parent global assessment of overall well-being assesses on a VAS from 0 (asymptomatic) to 10 (severe symptoms);&#xD;
Number of active joints;&#xD;
Number of joints with limitation of motion (LOM) and with pain, tenderness, or both;&#xD;
Childhood Health Assessment Questionnaire (CHAQ) disability domain;&#xD;
Erythrocyte sedimentation rate (ESR).</description>
          <population>All randomized participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0030</p_value>
            <method>Mantel Haenszel</method>
            <method_desc>Stratified by study center and the number of active joints at randomization</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Flare in Part 2</title>
        <description>The time from day 90 to flare. Participants who withdrew without flare were censored at the time of withdrawal.</description>
        <time_frame>Months 4 to 7</time_frame>
        <population>All randomized participants</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Placebo</title>
            <description>In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Etanercept 0.4 mg/kg</title>
            <description>In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Flare in Part 2</title>
          <description>The time from day 90 to flare. Participants who withdrew without flare were censored at the time of withdrawal.</description>
          <population>All randomized participants</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.0" lower_limit="6" upper_limit="123"/>
                    <measurement group_id="O2" value="116.0" lower_limit="28" upper_limit="127"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0001</p_value>
            <method>Log Rank</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <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).</time_frame>
        <population>All participants who received at least one dose of study drug</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Etanercept 0.4 mg/kg</title>
            <description>Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: Placebo</title>
            <description>In Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.</description>
          </group>
          <group group_id="O3">
            <title>Part 2: Etanercept 0.4 mg/kg</title>
            <description>In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <population>All participants who received at least one dose of study drug</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
                <count group_id="O2" value="26"/>
                <count group_id="O3" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Noninfectious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Injection site reactions</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infections</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Deaths</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_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).</time_frame>
      <desc>Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.</desc>
      <group_list>
        <group group_id="E1">
          <title>Part 1: Etanercept 0.4 mg/kg</title>
          <description>Participants received 0.4 mg/kg etanercept twice weekly for 90 days during Part 1.</description>
        </group>
        <group group_id="E2">
          <title>Part 2: Placebo</title>
          <description>n Part 2 participants were randomized to receive placebo subcutaneous injection twice weekly for up to 4 months.</description>
        </group>
        <group group_id="E3">
          <title>Part 2: Etanercept 0.4 mg/kg</title>
          <description>In Part 2 participants were randomized to continue receiving 0.4 mg/kg etanercept twice weekly for up to 4 additional months.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal behaviour</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="59" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Injection site pruritus</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Injection site swelling</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Tinea pedis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Vasculitic rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to1 review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Amgen Inc.</organization>
      <phone>866-572-6436</phone>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03780959
org study id: 20021616
secondary id: 016.0016
nct id: NCT03780959
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of this study was to determine the efficacy of etanercept in children
      with polyarticular course JRA.
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Percentage of Participants With Disease Flare in Part 2
time frame: End of part 1 (day 90) and months 4 to 7
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).
measure: Time to Flare in Part 2
time frame: Months 4 to 7
description: The time from day 90 to flare. Participants who withdrew without flare were censored at the time of withdrawal.
measure: 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).
arm group label: Etanercept/Placebo
arm group type: Placebo Comparator
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 group label: Etanercept/Etanercept
arm group type: Experimental
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: Etanercept
description: Administered twice weekly by subcutaneous injection
arm group label: Etanercept/Etanercept
arm group label: Etanercept/Placebo
other name: Enbrel
other name: TNFR:Fc
intervention type: Drug
intervention name: Placebo
description: Administered twice weekly by subcutaneous injection
arm group label: Etanercept/Placebo
criteria: 
gender: All
minimum age: 4 Years
maximum age: 18 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Arthritis, Juvenile
mesh term: Necrosis
mesh term: Etanercept
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 