<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/NCT01679951</url>
  </required_header>
  <id_info>
    <org_study_id>CR100734</org_study_id>
    <secondary_id>38518168ARA2002</secondary_id>
    <secondary_id>2011-002840-29</secondary_id>
    <nct_id>NCT01679951</nct_id>
  </id_info>
  <brief_title>A Dose Range Finding Study of JNJ-38518168 in Patients With Active Rheumatoid Arthritis in Spite of Treatment With Methotrexate</brief_title>
  <official_title>A Phase 2b Randomized, Double-blind, Multicenter, Placebo-controlled, Parallel Group, Dose Range Finding Study of JNJ-38518168 in Subjects With Active Rheumatoid Arthritis Despite Concomitant Methotrexate Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this dose range finding study is to assess the effectiveness, safety and&#xD;
      tolerability of JNJ-38518168 at doses of 3, 10, and 30 mg/d compared with placebo in patients&#xD;
      with active rheumatoid arthritis (RA) despite concomitant methotrexate (MTX) therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized (the study medication is assigned by chance), double-blind (neither&#xD;
      physician nor patient knows the treatment that the patient receives), multicenter,&#xD;
      placebo-controlled (an inactive substance that is compared with a drug to test whether the&#xD;
      drug has a real effect in a clinical trial), parallel-group (each group of patients will be&#xD;
      treated at the same time), dose range finding study of JNJ-38518168 in patients with active&#xD;
      RA despite concomitant MTX therapy. The study will consist a screening period, a 24-week&#xD;
      placebo-controlled period and a 4-week follow-up period between the last dose and the last&#xD;
      visit. The duration of participation in the study for an individual patient will be up to 34&#xD;
      weeks (including screening). The patients will be assigned to 1 of 4 treatment groups in a&#xD;
      1:1:1:1 ratio to placebo and JNJ-38518168 (3 mg or 10 mg or 30 mg). Safety assessments and&#xD;
      evaluations to determine the efficacy of JNJ-38518168 to reduce the signs and symptoms of RA&#xD;
      will be performed at study visits. Safety will be monitored throughout the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The decision was made to prematurely discontinue this trial due to lack of efficacy.&#xD;
  </why_stopped>
  <start_date type="Actual">October 31, 2012</start_date>
  <completion_date type="Actual">July 3, 2014</completion_date>
  <primary_completion_date type="Actual">April 17, 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease Activity Score 28 (DAS28) (C-reactive protein [CRP]) at Week 12</measure>
    <time_frame>Baseline and Week 12</time_frame>
    <description>The DAS28 using CRP is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and Patient's Global Assessment of Disease Activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in DAS28 (CRP) at Week 24</measure>
    <time_frame>Baseline and Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in DAS28 (erythrocyte sedimentation rate [ESR]) at Week 12 and Week 24</measure>
    <time_frame>Baseline, Week 12 and Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DAS28 (CRP) response rates at Week 12 and Week 24</measure>
    <time_frame>Week 12 and Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DAS28 (ESR) response rates at Week 12 and Week 24</measure>
    <time_frame>Week 12 and Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DAS28 (CRP) remission rates at Week 12 and Week 24</measure>
    <time_frame>Week 12 and Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DAS28 (ESR) remission rates at Week 12 and Week 24</measure>
    <time_frame>Week 12 and Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>American College of Rheumatology (ACR) 20/50/70 response rates at Week 12 and Week 24</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>An ACR 20/50/70 response is defined as a greater than or equal to 20/50/70 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hybrid ACR response at Week 12 and Week 24</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>The hybrid ACR response is a continuous variable that is limited to an overall score of -100 (maximal worsening) to +100 (maximal improvement).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>According to the ACR/EULAR provisional definition, a patients RA can be defined as being in remission based on either of 2 definitions:&#xD;
when scores on the tender joint count, swollen joint count, CRP (in mg/dL), and patient global assessment (0-10 scale) are all less than or equal to 1 OR when the score on the simplified disease activity index (SDAI) is less than or equal to 3.3 Analyses based on each definition will be performed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24</measure>
    <time_frame>Baseline, Week 12 and Week 24</time_frame>
    <description>The SDAI is the numerical sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient global assessment of disease activity (PGA VAS in cm), physician global assessment of disease activity (MDGA VAS in cm) and C-reactive protein (CRP in mg/dL).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24</measure>
    <time_frame>Baseline, Week 12 and Week 24</time_frame>
    <description>The CDAI is the numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA, and MDGA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24</measure>
    <time_frame>Week 12 and Week 24</time_frame>
    <description>The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in HAQ-DI score at Week 12 and Week 24</measure>
    <time_frame>Baseline, Week 12 and Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change from baseline in ESR levels at Week 12 and Week 24</measure>
    <time_frame>Baseline, Week 12 and Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent change from baseline in ACR components at Week 12 and Week 24</measure>
    <time_frame>Baseline, Week 12 and Week 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to Week 28</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">272</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>JNJ-38518168 (3 mg/d)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>JNJ-38518168 (10 mg/d)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>JNJ-38518168 (30 mg/d)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Form=tablet, route=oral. Placebo will be administered once daily from week 0 to week 24.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JNJ-38518168 (3 mg)</intervention_name>
    <description>Type=exact number, unit=mg, number=3, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.</description>
    <arm_group_label>JNJ-38518168 (3 mg/d)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JNJ-38518168 (10 mg)</intervention_name>
    <description>Type=exact number, unit=mg, number=10, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.</description>
    <arm_group_label>JNJ-38518168 (10 mg/d)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JNJ-38518168 (30 mg)</intervention_name>
    <description>Type=exact number, unit=mg, number=30, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.</description>
    <arm_group_label>JNJ-38518168 (30 mg/d)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>Participants must have been treated with and tolerated Methotrexate (MTX) treatment at dosages from 10 to 25 milligram per week (mg/week) inclusive, for a minimum of 6 months prior to the date of signing the informed consent at screening and must have a stable MTX dose for a minimum of 8 weeks prior to the date of signing the informed consent at screening and continue to receive the same MTX dose at Week 0 through Week 24.</description>
    <arm_group_label>JNJ-38518168 (10 mg/d)</arm_group_label>
    <arm_group_label>JNJ-38518168 (3 mg/d)</arm_group_label>
    <arm_group_label>JNJ-38518168 (30 mg/d)</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has had rheumatoid arthritis for at least 6 months prior to the date of signing the&#xD;
             informed consent at screening&#xD;
&#xD;
          -  Must be positive for either anti-cyclic citrullinated peptide antibody or rheumatoid&#xD;
             factor in serum at screening&#xD;
&#xD;
          -  Must have active rheumatoid arthritis (at least 6 swollen and 6 tender joints using a&#xD;
             66/68 joint count at the time of screening and at baseline and Serum C reactive&#xD;
             protein greater than or equal to 0.80 mg/dL at the time of screening&#xD;
&#xD;
          -  Has been treated with and tolerated methotrexate treatment at dosages from 10 to 25&#xD;
             mg/week inclusive, for a minimum of 6 months with stable dose for at least 8 weeks&#xD;
             prior to the date of signing the informed consent at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has inflammatory diseases other than rheumatoid arthritis, including but not limited&#xD;
             to adult onset Still's disease, psoriatic arthritis, ankylosing spondylitis, systemic&#xD;
             lupus erythematosus, and Lyme disease that might confound the evaluation of the&#xD;
             benefit of study agent therapy&#xD;
&#xD;
          -  Has current signs or symptoms of liver or renal insufficiency or cardiac, vascular,&#xD;
             pulmonary, gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or&#xD;
             metabolic disturbances that are severe, progressive or uncontrolled&#xD;
&#xD;
          -  Has ever received any approved or investigational biologic agent for a rheumatoid&#xD;
             indication&#xD;
&#xD;
          -  Has been treated with any nonbiologic disease modifying antirheumatic drugs within 4&#xD;
             weeks prior to the first administration of study agent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research and Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research and Development LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Huntsville</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Covina</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Palm Harbor</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Granger</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Frederick</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Freehold</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Miguel De Tucuman</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Osorno X Region</city>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Santiago - Macul</city>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Santiago</city>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Viña Del Mar</city>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barranquilla</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bogota</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bucaramanga</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cali</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Medellin</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Medellín</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hlucin</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ostrava</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Praha</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Slany</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zlin</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Balatonfured</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Debrecen</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gyulai</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Veszprem</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chiba</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fukuoka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hokkaido</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kanagawa</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kato</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kawagoe</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kumamoto</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kyoto</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Matsuyama</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Osaka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sapporo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Takasaki</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Daegu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Pucheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Suwon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Adazi</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Riga</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valmiera</city>
        <country>Latvia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Ciudad De Mexico</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Del Gustavo A Madero</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Delegación Cuauhtémoc</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Guadalajara, Jalisco</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Guadalajara</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Guadalaja</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Leon</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>México</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Luis Potosi</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bialystok</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Białystok</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Katowice</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nadarzyn</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Poznan</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sroda Wielkopolska</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Warszawa</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wroclaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bacau</city>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Braila</city>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bucuresti</city>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sibiu</city>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kazan</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Novosibirsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Petrozavodsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint-Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saratov</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Tver</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Yaroslavl</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kaohsiung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bangkok</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chiang Mai</city>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Donetsk</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kyiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Vinnytsya</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Chile</country>
    <country>Colombia</country>
    <country>Czechia</country>
    <country>Hungary</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Latvia</country>
    <country>Mexico</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>September 3, 2012</study_first_submitted>
  <study_first_submitted_qc>September 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 6, 2012</study_first_posted>
  <disposition_first_submitted>December 29, 2014</disposition_first_submitted>
  <disposition_first_submitted_qc>December 29, 2014</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">January 13, 2015</disposition_first_posted>
  <last_update_submitted>March 13, 2019</last_update_submitted>
  <last_update_submitted_qc>March 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rheumatoid arthritis</keyword>
  <keyword>Swollen and tender joints</keyword>
  <keyword>Methotrexate</keyword>
  <keyword>Immunology</keyword>
  <keyword>Dose range finding study</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methotrexate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT01679951
org study id: CR100734
secondary id: 38518168ARA2002
secondary id: 2011-002840-29
nct id: NCT01679951
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
The purpose of this dose range finding study is to assess the effectiveness, safety and
      tolerability of JNJ-38518168 at doses of 3, 10, and 30 mg/d compared with placebo in patients
      with active rheumatoid arthritis (RA) despite concomitant methotrexate (MTX) therapy.
This is a randomized (the study medication is assigned by chance), double-blind (neither
      physician nor patient knows the treatment that the patient receives), multicenter,
      placebo-controlled (an inactive substance that is compared with a drug to test whether the
      drug has a real effect in a clinical trial), parallel-group (each group of patients will be
      treated at the same time), dose range finding study of JNJ-38518168 in patients with active
      RA despite concomitant MTX therapy. The study will consist a screening period, a 24-week
      placebo-controlled period and a 4-week follow-up period between the last dose and the last
      visit. The duration of participation in the study for an individual patient will be up to 34
      weeks (including screening). The patients will be assigned to 1 of 4 treatment groups in a
      1:1:1:1 ratio to placebo and JNJ-38518168 (3 mg or 10 mg or 30 mg). Safety assessments and
      evaluations to determine the efficacy of JNJ-38518168 to reduce the signs and symptoms of RA
      will be performed at study visits. Safety will be monitored throughout the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Disease Activity Score 28 (DAS28) (C-reactive protein [CRP]) at Week 12
time frame: Baseline and Week 12
description: The DAS28 using CRP is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and Patient's Global Assessment of Disease Activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. The values are 0=best to 10=worst.
measure: Change from baseline in DAS28 (CRP) at Week 24
time frame: Baseline and Week 24
measure: Change from baseline in DAS28 (erythrocyte sedimentation rate [ESR]) at Week 12 and Week 24
time frame: Baseline, Week 12 and Week 24
measure: DAS28 (CRP) response rates at Week 12 and Week 24
time frame: Week 12 and Week 24
measure: DAS28 (ESR) response rates at Week 12 and Week 24
time frame: Week 12 and Week 24
measure: DAS28 (CRP) remission rates at Week 12 and Week 24
time frame: Week 12 and Week 24
measure: DAS28 (ESR) remission rates at Week 12 and Week 24
time frame: Week 12 and Week 24
measure: American College of Rheumatology (ACR) 20/50/70 response rates at Week 12 and Week 24
time frame: Week 12 and Week 24
description: An ACR 20/50/70 response is defined as a greater than or equal to 20/50/70 percentage improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity (VAS) (0-10 cm) c. Physician's Global Assessment of Disease Activity (VAS) (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein (CRP).
measure: Hybrid ACR response at Week 12 and Week 24
time frame: Week 12 and Week 24
description: The hybrid ACR response is a continuous variable that is limited to an overall score of -100 (maximal worsening) to +100 (maximal improvement).
measure: ACR/European League Against Rheumatism (EULAR) remission rates at Week 12 and Week 24
time frame: Week 12 and Week 24
description: According to the ACR/EULAR provisional definition, a patients RA can be defined as being in remission based on either of 2 definitions:
when scores on the tender joint count, swollen joint count, CRP (in mg/dL), and patient global assessment (0-10 scale) are all less than or equal to 1 OR when the score on the simplified disease activity index (SDAI) is less than or equal to 3.3 Analyses based on each definition will be performed.
measure: Change from baseline in Simplified Disease Activity Index (SDAI) at Week 12 and Week 24
time frame: Baseline, Week 12 and Week 24
description: The SDAI is the numerical sum of 5 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient global assessment of disease activity (PGA VAS in cm), physician global assessment of disease activity (MDGA VAS in cm) and C-reactive protein (CRP in mg/dL).
measure: Change from baseline in Clinical Disease Activity Index (CDAI) at Week 12 and Week 24
time frame: Baseline, Week 12 and Week 24
description: The CDAI is the numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA, and MDGA.
measure: Health Assessment Questionnaire - Disability Index (HAQ-DI) response at Week 12 and Week 24
time frame: Week 12 and Week 24
description: The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area).
measure: Change from baseline in HAQ-DI score at Week 12 and Week 24
time frame: Baseline, Week 12 and Week 24
measure: Percent change from baseline in ESR levels at Week 12 and Week 24
time frame: Baseline, Week 12 and Week 24
measure: Percent change from baseline in ACR components at Week 12 and Week 24
time frame: Baseline, Week 12 and Week 24
measure: Number of patients with adverse events
time frame: Up to Week 28
arm group label: Placebo
arm group type: Placebo Comparator
arm group label: JNJ-38518168 (3 mg/d)
arm group type: Experimental
arm group label: JNJ-38518168 (10 mg/d)
arm group type: Experimental
arm group label: JNJ-38518168 (30 mg/d)
arm group type: Experimental
intervention type: Drug
intervention name: Placebo
description: Form=tablet, route=oral. Placebo will be administered once daily from week 0 to week 24.
arm group label: Placebo
intervention type: Drug
intervention name: JNJ-38518168 (3 mg)
description: Type=exact number, unit=mg, number=3, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.
arm group label: JNJ-38518168 (3 mg/d)
intervention type: Drug
intervention name: JNJ-38518168 (10 mg)
description: Type=exact number, unit=mg, number=10, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.
arm group label: JNJ-38518168 (10 mg/d)
intervention type: Drug
intervention name: JNJ-38518168 (30 mg)
description: Type=exact number, unit=mg, number=30, form=tablet, route=oral. JNJ-38518168 will be administered once daily up to 24 weeks.
arm group label: JNJ-38518168 (30 mg/d)
intervention type: Drug
intervention name: Methotrexate
description: Participants must have been treated with and tolerated Methotrexate (MTX) treatment at dosages from 10 to 25 milligram per week (mg/week) inclusive, for a minimum of 6 months prior to the date of signing the informed consent at screening and must have a stable MTX dose for a minimum of 8 weeks prior to the date of signing the informed consent at screening and continue to receive the same MTX dose at Week 0 through Week 24.
arm group label: JNJ-38518168 (10 mg/d)
arm group label: JNJ-38518168 (3 mg/d)
arm group label: JNJ-38518168 (30 mg/d)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Janssen Research and Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research and Development LLC
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country: Argentina
country: Chile
country: Colombia
country: Czechia
country: Hungary
country: Japan
country: Korea, Republic of
country: Latvia
country: Mexico
country: Poland
country: Romania
country: Russian Federation
country: Taiwan
country: Thailand
country: Ukraine
country: United States
country: Czech Republic
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Methotrexate