<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/NCT01668641</url>
  </required_header>
  <id_info>
    <org_study_id>GLPG0634-CL-202</org_study_id>
    <nct_id>NCT01668641</nct_id>
  </id_info>
  <brief_title>Dose-ranging Study With GLPG0634 in Methotrexate-refractory Active Rheumatoid Arthritis Patients</brief_title>
  <official_title>Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II Study to Compare Four Dose Regimens of GLPG0634 Versus Placebo, in Combination With Methotrexate, Administered for 4 Weeks in the Treatment of Subjects With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Alone</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Galapagos NV</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Galapagos NV</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      -  Ninety patients suffering from active rheumatoid arthritis despite continued treatment&#xD;
           with methotrexate will be evaluated for improvement of disease activity when taking&#xD;
           GLPG0634 (4 different doses will be evaluated) or matching placebo for 4 weeks.&#xD;
&#xD;
        -  During the course of the study, patients will also be examined for any side effects that&#xD;
           may occur, and the amount of GLPG0634 present in the blood as well as the effects of&#xD;
           GLPG0634 on disease- and mechanism of action-related parameters in the blood will be&#xD;
           determined.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2012</start_date>
  <completion_date type="Actual">October 2012</completion_date>
  <primary_completion_date type="Actual">September 2012</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The number of patients with an ACR20 score at Week 4 as a measure of efficacy</measure>
    <time_frame>Week 4 (end of treatment visit)</time_frame>
    <description>To preliminary evaluate the efficacy of GLPG0634 compared to placebo in terms of the proportion of subjects achieving an ACR20 response at Week 4</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The number of patients with ACR20/50/70 response, time to response and DAS28 score at every visit as a measure of efficacy</measure>
    <time_frame>From Day -1 up to end of treatment visit (week 4)</time_frame>
    <description>To evaluate the efficacy of GLPG0634 compared to placebo in terms of ACR response criteria at every visit (ACR20, ACR50, ACR70), time to response, and disease status (DAS28[C-reactive protein, CRP]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of patients with adverse events, abnormal lab tests, vital signs and ECG as a measure of safety and tolerability</measure>
    <time_frame>From screening up to 10 days after last dose</time_frame>
    <description>To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of adverse events (AEs), laboratory test abnormalities, vital signs and electrocardiogram (ECG)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The plasma levels of GLPG0634 as a measure of PK</measure>
    <time_frame>Week 1, week 2 and week 4 visits</time_frame>
    <description>To characterize the pharmacokinetics (PK) of GLPG0634 by measuring the amount of GLPG0634 in the plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The plasma levels of GLPG0634 and MTX as a measure of PK</measure>
    <time_frame>Day -1 and Week 2 or 4 visit (8 hour-sampling)</time_frame>
    <description>To explore the potential interaction of GLPG0634 on MTX by assessing steady state PK in an 8-hour sampling at Day -1 and at Week 2 or Week 4 visit in a subset of patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The levels of immune- and inflammation-related parameters in plasma as a measure of PD</measure>
    <time_frame>Day -1, Week 1, week 2 and week 4 visits</time_frame>
    <description>To characterize the pharmacodynamics (PD) of GLPG0634 by measuring the levels of immune- and inflammation-related parameters in plasma</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">91</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>capsule, 30mg GLPG0634 once a day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 capsules of 10 mg once a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>capsules, 75mg GLPG0634 once a day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 capsules of 25mg once a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>capsules, 150mg GLPG0634 once a day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 capsules of 50mg once a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>capsules, 300mg GLPG0634 once a day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 capsules of 100mg once a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>capsules, placebo once a day</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>3 capsules placebo once a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GLPG0634</intervention_name>
    <arm_group_label>capsule, 30mg GLPG0634 once a day</arm_group_label>
    <arm_group_label>capsules, 150mg GLPG0634 once a day</arm_group_label>
    <arm_group_label>capsules, 300mg GLPG0634 once a day</arm_group_label>
    <arm_group_label>capsules, 75mg GLPG0634 once a day</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>capsules, placebo once a day</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have active RA as shown by five or more swollen joints (from the 66-joint count), five&#xD;
             or more tender joints (from 68-joint count), and a serum CRP ≥1.0 mg/dL;&#xD;
&#xD;
          -  Have received methotrexate for 12 weeks or longer and at a stable dose of 7.5 to 25&#xD;
             mg/week for at least 4 weeks prior to screening and willing to continue on this&#xD;
             regimen for the duration of the study;&#xD;
&#xD;
          -  If taking oral steroids, these should be at a dose ≤10 mg/day of prednisone or&#xD;
             prednisone equivalent and stable for at least 4 weeks prior to screening;&#xD;
&#xD;
          -  If taking non-steroidal anti-inflammatory drugs (NSAIDs), these must be at a stable&#xD;
             dose for at least 2 weeks prior to screening;&#xD;
&#xD;
          -  Female subjects must have a negative pregnancy test unless they are surgically sterile&#xD;
             or have been post-menopausal for at least one year;&#xD;
&#xD;
          -  Women of childbearing potential must use a medically acceptable means of birth control&#xD;
             and agree to continue its use during the study and for at least 12 weeks after the&#xD;
             last dose of study drug.&#xD;
&#xD;
          -  Sexually active men must agree to use a medically acceptable form of contraception&#xD;
             during the study and continue its use for at least 3 months after the last dose of&#xD;
             study drug; and&#xD;
&#xD;
          -  Able and willing to sign the informed consent prior to screening evaluations and agree&#xD;
             to schedule of assessments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment with disease-modifying antirheumatic drugs (DMARDs), other than background&#xD;
             methotrexate;&#xD;
&#xD;
          -  Current or previous RA treatment with a biological agent, with the exception of&#xD;
             biologics administered in a clinical study setting more than six months prior to&#xD;
             screening (12 months for rituximab or other B cell depleting agents);&#xD;
&#xD;
          -  Previous treatment at any time with a cytotoxic agent, other than methotrexate, before&#xD;
             screening;&#xD;
&#xD;
          -  Previous use of the study drug GLPG0634;&#xD;
&#xD;
          -  Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks&#xD;
             prior to screening;&#xD;
&#xD;
          -  Known hypersensitivity to study drug ingredients or a significant allergic reaction to&#xD;
             any drug as determined by the Investigator;&#xD;
&#xD;
          -  Positive serology for HIV1 or 2 or hepatitis B or C, or any history of hepatitis from&#xD;
             any cause with the exception of hepatitis A;&#xD;
&#xD;
          -  History of any inflammatory rheumatological disorders other than RA;&#xD;
&#xD;
          -  History of tuberculosis (TB) infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frédéric Vanhoutte, MD</last_name>
    <role>Study Director</role>
    <affiliation>Galapagos NV</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Budai Irgalamsrendi Korhaz, II. Reumatologia Osztaly</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orszagos Reumatologiai es Fizioterapias Intezet, I. Reumatologia Osztaly</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Markhot Ferenc Korhaz, Reumatologiai Osztaly</name>
      <address>
        <city>Eger</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pest Megyei Flor Ferenc Korhaz, Reumatologiai es Fizioterapias Osztaly</name>
      <address>
        <city>Kistarcsa</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IMSP Institutel de Cardiologie</name>
      <address>
        <city>Chisinau</city>
        <country>Moldova, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Healthcare Institution of city Moscow 'City Clinical Hospital #7'</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Healthcare Institution 'Ryazan Regional Cardiology Dispensary'</name>
      <address>
        <city>Ryazan</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Petersburg State Healthcare Institution 'City Hospital #26'</name>
      <address>
        <city>Saint-Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Petersburg State Healthcare Institution 'City Mariinskiy Hospital'</name>
      <address>
        <city>Saint-Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Municipal Clinical Healthcare Institution 'Medical-Sanitary Unit of Novoyaroslavskiy Oil Refinery'</name>
      <address>
        <city>Yaroslavl</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chernivtsi Regional Clinical Hospital</name>
      <address>
        <city>Chernivtsi</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Institution 'Institute of Urgent and Recovery Surgery n.a. V.K. Gusaka' of AMS of Ukraine</name>
      <address>
        <city>Donetsk</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Institution of Healthcare</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institution of Therapy of AMS of Ukraine</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Institution 'Institute of Microbiology and Immunology of AMS of Ukraine'</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Institution 'Republican Clinical Hospital of MoH of Ukraine'</name>
      <address>
        <city>Kiev</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lutsk City Clinical Hospital</name>
      <address>
        <city>Lutsk</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vinnytsa Regional Clinical Hospital</name>
      <address>
        <city>Vinnytsa</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zaporizhzhia Regional Clinical Hospital</name>
      <address>
        <city>Zaporizhzhia</city>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hungary</country>
    <country>Moldova, Republic of</country>
    <country>Russian Federation</country>
    <country>Ukraine</country>
  </location_countries>
  <verification_date>June 2013</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <last_update_submitted>June 26, 2013</last_update_submitted>
  <last_update_submitted_qc>June 26, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 27, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Methotrexate insufficient responders</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>
  <!-- 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/NCT01668641
org study id: GLPG0634-CL-202
nct id: NCT01668641
lead sponsor: 
has dmc: No
-  Ninety patients suffering from active rheumatoid arthritis despite continued treatment
           with methotrexate will be evaluated for improvement of disease activity when taking
           GLPG0634 (4 different doses will be evaluated) or matching placebo for 4 weeks.

        -  During the course of the study, patients will also be examined for any side effects that
           may occur, and the amount of GLPG0634 present in the blood as well as the effects of
           GLPG0634 on disease- and mechanism of action-related parameters in the blood will be
           determined.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The number of patients with an ACR20 score at Week 4 as a measure of efficacy
time frame: Week 4 (end of treatment visit)
description: To preliminary evaluate the efficacy of GLPG0634 compared to placebo in terms of the proportion of subjects achieving an ACR20 response at Week 4
measure: The number of patients with ACR20/50/70 response, time to response and DAS28 score at every visit as a measure of efficacy
time frame: From Day -1 up to end of treatment visit (week 4)
description: To evaluate the efficacy of GLPG0634 compared to placebo in terms of ACR response criteria at every visit (ACR20, ACR50, ACR70), time to response, and disease status (DAS28[C-reactive protein, CRP]
measure: The number of patients with adverse events, abnormal lab tests, vital signs and ECG as a measure of safety and tolerability
time frame: From screening up to 10 days after last dose
description: To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of adverse events (AEs), laboratory test abnormalities, vital signs and electrocardiogram (ECG)
measure: The plasma levels of GLPG0634 as a measure of PK
time frame: Week 1, week 2 and week 4 visits
description: To characterize the pharmacokinetics (PK) of GLPG0634 by measuring the amount of GLPG0634 in the plasma
measure: The plasma levels of GLPG0634 and MTX as a measure of PK
time frame: Day -1 and Week 2 or 4 visit (8 hour-sampling)
description: To explore the potential interaction of GLPG0634 on MTX by assessing steady state PK in an 8-hour sampling at Day -1 and at Week 2 or Week 4 visit in a subset of patients
measure: The levels of immune- and inflammation-related parameters in plasma as a measure of PD
time frame: Day -1, Week 1, week 2 and week 4 visits
description: To characterize the pharmacodynamics (PD) of GLPG0634 by measuring the levels of immune- and inflammation-related parameters in plasma
arm group label: capsule, 30mg GLPG0634 once a day
arm group type: Experimental
description: 3 capsules of 10 mg once a day
arm group label: capsules, 75mg GLPG0634 once a day
arm group type: Experimental
description: 3 capsules of 25mg once a day
arm group label: capsules, 150mg GLPG0634 once a day
arm group type: Experimental
description: 3 capsules of 50mg once a day
arm group label: capsules, 300mg GLPG0634 once a day
arm group type: Experimental
description: 3 capsules of 100mg once a day
arm group label: capsules, placebo once a day
arm group type: Placebo Comparator
description: 3 capsules placebo once a day
intervention type: Drug
intervention name: GLPG0634
arm group label: capsule, 30mg GLPG0634 once a day
arm group label: capsules, 150mg GLPG0634 once a day
arm group label: capsules, 300mg GLPG0634 once a day
arm group label: capsules, 75mg GLPG0634 once a day
intervention type: Drug
intervention name: Placebo
arm group label: capsules, placebo once a day
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Frédéric Vanhoutte, MD
role: Study Director
affiliation: Galapagos NV
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Hungary
country: Moldova, Republic of
country: Russian Federation
country: Ukraine
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid