<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/NCT03301883</url>
  </required_header>
  <id_info>
    <org_study_id>YA39368</org_study_id>
    <nct_id>NCT03301883</nct_id>
  </id_info>
  <brief_title>A Study of Tocilizumab in Chinese Participants With Systemic Juvenile Idiopathic Arthritis (sJIA)</brief_title>
  <official_title>A Phase IV, Multicenter, Single-Arm, Open-Label Study to Assess the Efficacy and Safety of Tocilizumab in Chinese Patients With Systemic Juvenile Idiopathic Arthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase IV, multicenter, single-arm, open-label study will evaluate the efficacy and&#xD;
      safety of tocilizumab in Chinese participants with sJIA with persistent activity and an&#xD;
      inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs) and steroid therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 26, 2018</start_date>
  <completion_date type="Actual">August 5, 2022</completion_date>
  <primary_completion_date type="Actual">September 4, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 (JIA ACR30) Response With Absence of Fever, at Week 12</measure>
    <time_frame>Week 12</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving JIA ACR30 Response With Absence of Fever, at Week 52</measure>
    <time_frame>Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With 30 Percent (%), 50%, 70%, and 90% Improvement From Baseline in JIA Core Set Parameters</measure>
    <time_frame>Baseline, Weeks 12, 24, and 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Inactive Disease Assessed According to Criteria for Inactive Disease and Clinical Remission of sJIA (Wallace et. al. 2011 Criteria)</measure>
    <time_frame>Weeks 24 and 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Clinical Remission Assessed According to Criteria for Inactive Disease and Clinical Remission of sJIA (Wallace et. al. 2011 Criteria)</measure>
    <time_frame>Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With an Elevated High-Sensitivity C-Reactive Protein (hsCRP) Levels at Baseline Who Have Normal hsCRP Levels at Weeks 12, 24, and 52</measure>
    <time_frame>Baseline, Weeks 12, 24, and 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Glucocorticoid Dose</measure>
    <time_frame>Baseline up to Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Methotrexate (MTX) Dose</measure>
    <time_frame>Baseline up to Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Glucocorticoid Dose</measure>
    <time_frame>From Baseline to Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in MTX Dose</measure>
    <time_frame>From Baseline to Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Visual Analog Scale (VAS) Score</measure>
    <time_frame>Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pain VAS Score</measure>
    <time_frame>Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Discontinue Permitted Concomitant Medication for sJIA</measure>
    <time_frame>Baseline up to Week 52</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adverse Events (AEs)</measure>
    <time_frame>Baseline up to end of study (up to Week 60)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Juvenile Idiopathic Arthritis</condition>
  <arm_group>
    <arm_group_label>Tocilizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants weighing greater than or equal to (&gt;/=) 30 kilograms (kg) will receive tocilizumab 8 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks (Q2W), and participants weighing less than (&lt;) 30 kg will receive tocilizumab 12 mg/kg IV infusion Q2W for 52 weeks. After Week 12, the dose of tocilizumab can be adjusted for non-transient changes in body weight (shifting from &lt;30 to &gt;/=30 kg) over a minimum of three consecutive dosing visits. MTX, NSAIDs, and oral corticosteroids (CSs) are permitted but not required during the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab</intervention_name>
    <description>Tocilizumab will be administered as per the schedule specified in the arm description.</description>
    <arm_group_label>Tocilizumab</arm_group_label>
    <other_name>RO4877533</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NSAIDs</intervention_name>
    <description>Participants may receive NSAIDs up to the maximum recommended stable daily dose. Study protocol does not enforce any particular NSAID.</description>
    <arm_group_label>Tocilizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CSs</intervention_name>
    <description>Participants may receive CSs at a stable dose of 30 milligrams per day (mg/day) or 0.5 milligrams per kilogram per day (mg/kg/day), whichever is less. Study protocol does not enforce any particular CS.</description>
    <arm_group_label>Tocilizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MTX</intervention_name>
    <description>Participants may receive MTX at a stable dose of less than or equal to (&lt;/=) 20 milligrams per square meter (mg/m^2).</description>
    <arm_group_label>Tocilizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants meeting International League of Associations for Rheumatology (ILAR)&#xD;
             classification for sJIA&#xD;
&#xD;
          -  Greater than (&gt;) 6 months of documented persistent sJIA activity prior to screening&#xD;
&#xD;
          -  Active disease&#xD;
&#xD;
          -  hsCRP &gt;4.3 milligrams per liter (mg/L) or 0.43 milligrams per deciliter (mg/dL)&#xD;
&#xD;
          -  Participant who has recovered from any symptomatic serositis for at least 30 days&#xD;
             prior to the screening visit, and requires a dose of CSs at baseline of &lt;/=30 mg/day&#xD;
             or &lt;/=0.5 mg/kg/day, whichever is less&#xD;
&#xD;
          -  Participants meeting one of the following: Participant who is not receiving MTX or&#xD;
             discontinued MTX &gt;/=4 weeks prior to baseline visit; participant who has been taking&#xD;
             MTX &gt;/=12 weeks immediately prior to the baseline visit and on a stable dose of &lt;/=20&#xD;
             mg/m^2 for &gt;/=8 weeks prior to the baseline visit, together with either folic acid or&#xD;
             folinic acid according to local standard of care&#xD;
&#xD;
          -  Participant who was never treated with biologics or, if was previously treated with&#xD;
             biologics, discontinued etanercept (or Yisaipu, Qiangke, or Anbainuo) &gt;/=2 weeks,&#xD;
             infliximab or adalimumab &gt;/=8 weeks, anakinra &gt;/=1 week, or abatacept &gt;/=12 weeks&#xD;
             prior to the baseline visit&#xD;
&#xD;
          -  Participant who is not currently receiving oral CSs, or is taking oral CSs at a stable&#xD;
             dose for &gt;/=2 weeks prior to the baseline visit at &lt;/=30 mg/day or &lt;/=0.5 mg/kg/day,&#xD;
             whichever is less&#xD;
&#xD;
          -  Participant who is not taking NSAIDs, or taking &lt;/=1 type of NSAID at a stable dose&#xD;
             for &gt;/=2 weeks prior to the baseline visit and is less than or equal to the maximum&#xD;
             recommended daily dose&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Wheelchair bound or bedridden participant&#xD;
&#xD;
          -  Any other autoimmune, rheumatic disease, or overlap syndrome other than sJIA&#xD;
&#xD;
          -  Participant who is not fully recovered from recent surgery or &lt;6 weeks since surgery&#xD;
             at the time of screening visit; or planned surgery during the initial 12 weeks of the&#xD;
             study&#xD;
&#xD;
          -  Lack of peripheral venous access&#xD;
&#xD;
          -  Any significant concurrent medical or surgical condition that would jeopardize the&#xD;
             participant's safety or ability to complete the trial&#xD;
&#xD;
          -  Evidence of serious uncontrolled concomitant diseases&#xD;
&#xD;
          -  Asthma for which the participant has required the use of oral or parenteral CSs for&#xD;
             &gt;/=2 weeks within 6 months prior to the baseline visit&#xD;
&#xD;
          -  Known human immunodeficiency (HIV) infection or other acquired forms of immune&#xD;
             compromise or congenital conditions characterized by a compromised immune system&#xD;
&#xD;
          -  Any active acute, subacute, chronic, or recurrent bacterial, mycobacterial, viral, or&#xD;
             systemic fungal infection or opportunistic infection&#xD;
&#xD;
          -  Any major episode of infection requiring hospitalization or treatment during&#xD;
             screening, treatment with IV antibiotics completing within 4 weeks of the screening&#xD;
             visit, or oral antibiotics completing within 2 weeks of the screening visit&#xD;
&#xD;
          -  History of atypical tuberculosis (TB)&#xD;
&#xD;
          -  Active TB requiring treatment within 2 years prior to screening visit&#xD;
&#xD;
          -  Positive purified protein derivative (PPD) or T-spot test (interferon-gamma&#xD;
             [IFN-γ]-based test) at screen&#xD;
&#xD;
          -  Positive for latent TB&#xD;
&#xD;
          -  History of reactivation or new onset of a systemic infection such as herpes zoster or&#xD;
             Epstein-Barr virus (EBV) within 2 months of the screening visit&#xD;
&#xD;
          -  Hepatitis B surface antigen (Ag)- or hepatitis C antibody (Ab)-positive&#xD;
&#xD;
          -  History of macrophage activation syndrome (MAS) within 3 months prior to the screening&#xD;
             visit&#xD;
&#xD;
          -  Evidence of active malignant disease or diagnosed malignancies&#xD;
&#xD;
          -  Uncontrolled diabetes mellitus&#xD;
&#xD;
          -  Previous treatment with tocilizumab&#xD;
&#xD;
          -  Intra-articular, intramuscular, IV, or long-acting CSs administration within 28 days&#xD;
             prior to the baseline visit&#xD;
&#xD;
          -  Treatment with non-biologic disease-modifying antirheumatic drugs (DMARDs; other than&#xD;
             MTX) within 6 weeks prior to the baseline visit&#xD;
&#xD;
          -  Treatment with leflunomide that was not followed by standardized cholestyramine&#xD;
             washout and documented to be below the limit of detection prior to the baseline visit&#xD;
&#xD;
          -  Treatment with cyclophosphamide, etoposide (VP16) and statins within 90 days prior to&#xD;
             the baseline visit&#xD;
&#xD;
          -  Treatment with growth hormone and androgens within 4 weeks prior to the baseline visit&#xD;
&#xD;
          -  Administration of IV immunoglobulin within 28 days prior to the baseline visit&#xD;
&#xD;
          -  Treatment with any cell-depleting therapies&#xD;
&#xD;
          -  Stem cell transplant at any time&#xD;
&#xD;
          -  Participant who has received live or attenuated vaccines within 4 weeks prior to the&#xD;
             baseline visit, or intending to receive while on study drug or 3 months following the&#xD;
             last dose of study drug&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Capital Institute of Pediatrics</name>
      <address>
        <city>Beijing City</city>
        <zip>100020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Children's Hospital, Capital Medical University; rheumatism</name>
      <address>
        <city>Beijing City</city>
        <zip>100045</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Hospital of Jilin University</name>
      <address>
        <city>Changchun City</city>
        <zip>130021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital Chongqing Medical university</name>
      <address>
        <city>Chongqing City</city>
        <zip>400014</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Pediatric Rheumatology division</name>
      <address>
        <city>Guangzhou City</city>
        <zip>510120</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospibal ZheJiang University School of Medicine</name>
      <address>
        <city>Hangzhou City</city>
        <zip>310052</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chilren's hospital of nanjing medical university; Rheumatoid immunology</name>
      <address>
        <city>Nanjing</city>
        <zip>210000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Children's Medical Center; Renal rheumatology</name>
      <address>
        <city>Shanghai City</city>
        <zip>200127</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Fudan University</name>
      <address>
        <city>Shanghai</city>
        <zip>201102</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical College</name>
      <address>
        <city>Wenzhou</city>
        <zip>325000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>October 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <last_update_submitted>February 6, 2023</last_update_submitted>
  <last_update_submitted_qc>February 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</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, Juvenile</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03301883
org study id: YA39368
nct id: NCT03301883
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This Phase IV, multicenter, single-arm, open-label study will evaluate the efficacy and
      safety of tocilizumab in Chinese participants with sJIA with persistent activity and an
      inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs) and steroid therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30 (JIA ACR30) Response With Absence of Fever, at Week 12
time frame: Week 12
measure: Percentage of Participants Achieving JIA ACR30 Response With Absence of Fever, at Week 52
time frame: Week 52
measure: Percentage of Participants With 30 Percent (%), 50%, 70%, and 90% Improvement From Baseline in JIA Core Set Parameters
time frame: Baseline, Weeks 12, 24, and 52
measure: Percentage of Participants With Inactive Disease Assessed According to Criteria for Inactive Disease and Clinical Remission of sJIA (Wallace et. al. 2011 Criteria)
time frame: Weeks 24 and 52
measure: Percentage of Participants With Clinical Remission Assessed According to Criteria for Inactive Disease and Clinical Remission of sJIA (Wallace et. al. 2011 Criteria)
time frame: Week 52
measure: Percentage of Participants With an Elevated High-Sensitivity C-Reactive Protein (hsCRP) Levels at Baseline Who Have Normal hsCRP Levels at Weeks 12, 24, and 52
time frame: Baseline, Weeks 12, 24, and 52
measure: Mean Glucocorticoid Dose
time frame: Baseline up to Week 52
measure: Mean Methotrexate (MTX) Dose
time frame: Baseline up to Week 52
measure: Change From Baseline in Glucocorticoid Dose
time frame: From Baseline to Week 52
measure: Change From Baseline in MTX Dose
time frame: From Baseline to Week 52
measure: Pain Visual Analog Scale (VAS) Score
time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Change From Baseline in Pain VAS Score
time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: Percentage of Participants Who Discontinue Permitted Concomitant Medication for sJIA
time frame: Baseline up to Week 52
measure: Percentage of Participants With Adverse Events (AEs)
time frame: Baseline up to end of study (up to Week 60)
arm group label: Tocilizumab
arm group type: Experimental
description: Participants weighing greater than or equal to (>/=) 30 kilograms (kg) will receive tocilizumab 8 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks (Q2W), and participants weighing less than (<) 30 kg will receive tocilizumab 12 mg/kg IV infusion Q2W for 52 weeks. After Week 12, the dose of tocilizumab can be adjusted for non-transient changes in body weight (shifting from <30 to >/=30 kg) over a minimum of three consecutive dosing visits. MTX, NSAIDs, and oral corticosteroids (CSs) are permitted but not required during the study.
intervention type: Drug
intervention name: Tocilizumab
description: Tocilizumab will be administered as per the schedule specified in the arm description.
arm group label: Tocilizumab
other name: RO4877533
intervention type: Drug
intervention name: NSAIDs
description: Participants may receive NSAIDs up to the maximum recommended stable daily dose. Study protocol does not enforce any particular NSAID.
arm group label: Tocilizumab
intervention type: Drug
intervention name: CSs
description: Participants may receive CSs at a stable dose of 30 milligrams per day (mg/day) or 0.5 milligrams per kilogram per day (mg/kg/day), whichever is less. Study protocol does not enforce any particular CS.
arm group label: Tocilizumab
intervention type: Drug
intervention name: MTX
description: Participants may receive MTX at a stable dose of less than or equal to (</=) 20 milligrams per square meter (mg/m^2).
arm group label: Tocilizumab
criteria: 
gender: All
minimum age: 2 Years
maximum age: 17 Years
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Juvenile