<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/NCT03241108</url>
  </required_header>
  <id_info>
    <org_study_id>NI-0101-04</org_study_id>
    <secondary_id>2016-005017-45</secondary_id>
    <nct_id>NCT03241108</nct_id>
  </id_info>
  <brief_title>Study of an Anti-TLR4 mAb in Rheumatoid Arthritis</brief_title>
  <official_title>Randomized, Placebo-Controlled, Double Blind, Multicenter Phase 2 Study to Explore Tolerability, Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Intravenous Multiple Infusions of NI-0101, an Anti-Toll Like Receptor 4 Monoclonal Antibody in Patients With Rheumatoid Arthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Light Chain Bioscience - Novimmune SA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Light Chain Bioscience - Novimmune SA</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 is a Phase 2, PoC, randomized, placebo-controlled, double blind, international&#xD;
      multicentre study to explore the effect of a new antibody to treat patients with Rheumatoid&#xD;
      Arthritis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study foresees the randomization of at least 81 moderate to severe, ACPA positive, RA&#xD;
      patients who are inadequate responders to MTX, in two double blind arms (NI-0101:placebo,&#xD;
      with a ratio of 2:1). Patients will receive NI-0101 or placebo infusions up to a maximum of 6&#xD;
      administrations (every two weeks for 12 weeks). All patients will continue receiving a stable&#xD;
      dose of MTX. After 12 weeks, patients will enter the follow up period with monthly visits for&#xD;
      a minimum of 12 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 10, 2017</start_date>
  <completion_date type="Actual">June 20, 2018</completion_date>
  <primary_completion_date type="Actual">June 20, 2018</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence, severity, causality and outcomes of Adverse Events (AEs)</measure>
    <time_frame>From screening up to 24 weeks after first treatment administration</time_frame>
    <description>Incidence, severity, causality and outcomes of Adverse Events (AEs) (serious and non-serious), with particular attention being paid to infusion-related reactions and infections</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Withdrawal for safety reasons</measure>
    <time_frame>From randomization up to 24 weeks after first treatment administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Evolution of laboratory parameters</measure>
    <time_frame>From screening up to 24 weeks after first treatment administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Level of potential circulating antibodies against NI-0101</measure>
    <time_frame>From screening up to 24 weeks after first treatment administration</time_frame>
    <description>Level of potential circulating antibodies against NI-0101 to determine immunogenicity; i.e. the development of anti-drug antibodies (ADA).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Levels of CRP</measure>
    <time_frame>From screening up to 24 weeks after first treatment administration</time_frame>
    <description>Levels of C-Reactive protein (CRP)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Levels of inflammatory cytokines/chemokines</measure>
    <time_frame>From screening up to 24 weeks after first treatment administration</time_frame>
    <description>IL-6, TNFa, IP-10, MCP-1, sICAM, CXCL13</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DAS28 CRP</measure>
    <time_frame>From screening to 24 weeks after first treatment administration</time_frame>
    <description>Measure of Disease Activity Scores (DAS) for Rheumatism in 28 tender or swollen joints and C-Reactive protein (CRP) - DAS28-CRP</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ACR criteria</measure>
    <time_frame>From randomization to 24 weeks after first treatment administration</time_frame>
    <description>Proportion of patients achieving American College of Rheumatology Criteria (ACR20, ACR50 and ACR70)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of patient achieving remission</measure>
    <time_frame>From randomization to 24 weeks after first treatment administration</time_frame>
    <description>Proportion of patient achieving remission (defined as DAS28 &lt; 2.6)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>EULAR response</measure>
    <time_frame>From randomization to 24 weeks after first treatment administration</time_frame>
    <description>Proportion of patients achieving European League Against Rheumatism (EULAR) response criteria - good, moderate and no response</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Joint Count</measure>
    <time_frame>From screening to 24 weeks after first treatment administration</time_frame>
    <description>Mean number of Tender Joint Count/Swollen Joint Count.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SDAI score</measure>
    <time_frame>From randomization to 24 weeks after first treatment administration</time_frame>
    <description>Mean improvement from baseline in Simplified Disease Activity Index (SDAI) score</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HAQ-DI score</measure>
    <time_frame>From randomization to 24 weeks after first treatment administration</time_frame>
    <description>Mean improvement from baseline in the Health Assessment Questionnaire without Disability Index (HAQ-DI) score</description>
  </primary_outcome>
  <primary_outcome>
    <measure>SF-36 score</measure>
    <time_frame>from randomization to 24 weeks after first treatment administration</time_frame>
    <description>Mean improvement from baseline in 36-Item Short-Form Health Survey (SF-36) score</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DAS28-ESR</measure>
    <time_frame>From screening to 24 weeks after first treatment administration</time_frame>
    <description>Measure of Disease Activity Scores (DAS) for Rheumatism in 28 tender or swollen joints and Erythrocyte Sedimentation Rate (ESR) levels - DAS28-ESR</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CDAI score</measure>
    <time_frame>From randomization to 24 weeks after first treatment administration</time_frame>
    <description>Mean improvement from baseline in Clinical Disease Activity Index (CDAI) score scores</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Exploratory PK analysis - Cmax</measure>
    <time_frame>From randomization to 24 weeks after first treatment administration</time_frame>
    <description>Peak drug plasma concentration (Cmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Exploratory PK analysis - Tmax</measure>
    <time_frame>From screening up to 24 weeks after first treatment administration</time_frame>
    <description>Time when plasma concentration is at peak (Tmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Exploratory PK analysis - Ctrough</measure>
    <time_frame>From randomization to 24 weeks after first treatment administration</time_frame>
    <description>Plasma drug concentration immediately prior next dosing (Ctrough)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Exploratory PK analysis - AUC</measure>
    <time_frame>From randomization to 24 weeks after first treatment administration</time_frame>
    <description>Area under the plasma concentration versus time curve (AUC)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Exploratory PK analysis - CL</measure>
    <time_frame>From randomization to 24 weeks after first treatment administration</time_frame>
    <description>Systemic drug clearance (CL)</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>NI-0101</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A therapeutic humanized monoclonal antibody, administered by intravenous infusion every 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo matches NI-0101 without active ingredient, administered by intravenous infusion every 2 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NI-0101</intervention_name>
    <description>Humanized immunoglobulin gamma 1 (IgG1) kappa monoclonal antibody targeting TLR4</description>
    <arm_group_label>NI-0101</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients&#xD;
&#xD;
          -  Age &gt;= 18 years old&#xD;
&#xD;
          -  BMI: &lt; 30 and &gt; 18&#xD;
&#xD;
          -  Diagnosis of RA according to 2010 ACR/EULAR criteria and with a disease duration of at&#xD;
             least 6 months since diagnosis&#xD;
&#xD;
          -  Patient must present with active RA, characterized by at least 6 swollen joints out of&#xD;
             66 assessed and 6 tender joints out of 68 assessed and by the presence of synovitis&#xD;
             (measured by ultrasound) in at least one of the 6 swollen joints&#xD;
&#xD;
          -  C-reactive protein (CRP) level &gt; 0.7 mg/dL or if the CRP level is between 0.3 mg/dL&#xD;
             and 0.7 mg/dL (included) then patient must also present an ESR &gt; 30mm/hr&#xD;
&#xD;
          -  Patients must have received MTX treatment for at least 3 months and have been on a&#xD;
             stable dose of MTX for at least 6 weeks prior to start of screening&#xD;
&#xD;
          -  ACPA-positive RA patients&#xD;
&#xD;
          -  Women must be postmenopausal (&gt; 12 months without menses) or surgically sterile or&#xD;
             using two effective contraception methods for at least 4 weeks prior to the&#xD;
             randomization date and agree to continue contraception for the duration of their&#xD;
             participation in the study (until the end of follow up period)&#xD;
&#xD;
          -  Sexually active male patients must use a barrier method of contraception during the&#xD;
             course of the study (and until the end of the follow up period)&#xD;
&#xD;
          -  Patients must give written informed consent for study participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A documented history of an autoimmune disease other than RA by ACR classification, or&#xD;
             Sjögren syndrome&#xD;
&#xD;
          -  Administration of cytotoxic drugs and immune suppressants (other than MTX) within 3&#xD;
             months prior to screening&#xD;
&#xD;
          -  Previous multiple administrations of any biological DMARD or targeted synthetic DMARD&#xD;
&#xD;
          -  Known primary immunodeficiency&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Suspicion of active or latent tuberculosis&#xD;
&#xD;
          -  HIV, HCV, HBV infection&#xD;
&#xD;
          -  Infection reported during screening not recovered 72h prior to first dose&#xD;
&#xD;
          -  History of anaphylactic reactions to any protein therapeutics or excipients&#xD;
&#xD;
          -  Any history of malignancy, excluding cured basal or squamous cell carcinoma of the&#xD;
             skin, or cervical in situ carcinoma&#xD;
&#xD;
          -  Clinically significant cardiac disease requiring medication, such as congestive heart&#xD;
             failure, unstable angina, myocardial infarction within 6 months prior to randomization&#xD;
&#xD;
          -  Moderate to severe renal insufficiency, clinically relevant liver function test&#xD;
             abnormalities or pancytopenia&#xD;
&#xD;
          -  Major psychiatric or neurological disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ernest Choy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Infection and Immunity, Cardiff University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinic for internal medicine with centre for dialysis</name>
      <address>
        <city>Mostar</city>
        <zip>88000</zip>
        <country>Bosnia and Herzegovina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multi-profile Hospital for Active Treatment &quot;Trimontsium&quot;</name>
      <address>
        <city>Plovdiv</city>
        <zip>4000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Multiprofile Hospital for Active Treatment &quot;Kaspela&quot;</name>
      <address>
        <city>Plovdiv</city>
        <zip>4001</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment - Shumen AD</name>
      <address>
        <city>Shumen</city>
        <zip>9705</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Multiprofile Hospital for Active TreatmenT &quot;St. Ivan Rilski&quot;</name>
      <address>
        <city>Sofia</city>
        <zip>1612</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ARENSIA Phase I Unit at the Research Institute of Clinical Medicine</name>
      <address>
        <city>Tbilisi</city>
        <zip>0112</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>High Technology Medical Center; University clinic</name>
      <address>
        <city>Tbilisi</city>
        <zip>0144</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emergency Cardiology Center by Acad. G.Chapidze</name>
      <address>
        <city>Tbilisi</city>
        <zip>0159</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Insitute of Clinical Cardiology</name>
      <address>
        <city>Tbilisi</city>
        <zip>0159</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tbilisi Central Hospital</name>
      <address>
        <city>Tbilisi</city>
        <zip>0159</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Clinic Consilium Medulla</name>
      <address>
        <city>Tbilisi</city>
        <zip>0186</zip>
        <country>Georgia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRU Hungary Ltd</name>
      <address>
        <city>Miskolc</city>
        <zip>3529</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republican Clinical Hospital, ARENSIA Phase I unit</name>
      <address>
        <city>Chisinau</city>
        <zip>MD2025</zip>
        <country>Moldova, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Miriada</name>
      <address>
        <city>Bialystok</city>
        <zip>15-297</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zespól Poradni Specjalistycznych REUMED</name>
      <address>
        <city>Lublin</city>
        <zip>20-582</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Rheumatology</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Kragujevac</name>
      <address>
        <city>Kragujevac</city>
        <zip>34000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Special Hospital for Rheumatic Diseases &quot;Novi Sad&quot;</name>
      <address>
        <city>Novi Sad</city>
        <zip>21112</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>General Hospital &quot;Djordje Joanovic&quot;</name>
      <address>
        <city>Zrenjanin</city>
        <zip>23000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bosnia and Herzegovina</country>
    <country>Bulgaria</country>
    <country>Georgia</country>
    <country>Hungary</country>
    <country>Moldova, Republic of</country>
    <country>Poland</country>
    <country>Serbia</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>June 26, 2017</study_first_submitted>
  <study_first_submitted_qc>August 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>August 13, 2018</last_update_submitted>
  <last_update_submitted_qc>August 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2018</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>
  </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/NCT03241108
org study id: NI-0101-04
secondary id: 2016-005017-45
nct id: NCT03241108
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a Phase 2, PoC, randomized, placebo-controlled, double blind, international
      multicentre study to explore the effect of a new antibody to treat patients with Rheumatoid
      Arthritis
The study foresees the randomization of at least 81 moderate to severe, ACPA positive, RA
      patients who are inadequate responders to MTX, in two double blind arms (NI-0101:placebo,
      with a ratio of 2:1). Patients will receive NI-0101 or placebo infusions up to a maximum of 6
      administrations (every two weeks for 12 weeks). All patients will continue receiving a stable
      dose of MTX. After 12 weeks, patients will enter the follow up period with monthly visits for
      a minimum of 12 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Incidence, severity, causality and outcomes of Adverse Events (AEs)
time frame: From screening up to 24 weeks after first treatment administration
description: Incidence, severity, causality and outcomes of Adverse Events (AEs) (serious and non-serious), with particular attention being paid to infusion-related reactions and infections
measure: Withdrawal for safety reasons
time frame: From randomization up to 24 weeks after first treatment administration
measure: Evolution of laboratory parameters
time frame: From screening up to 24 weeks after first treatment administration
measure: Level of potential circulating antibodies against NI-0101
time frame: From screening up to 24 weeks after first treatment administration
description: Level of potential circulating antibodies against NI-0101 to determine immunogenicity; i.e. the development of anti-drug antibodies (ADA).
measure: Levels of CRP
time frame: From screening up to 24 weeks after first treatment administration
description: Levels of C-Reactive protein (CRP)
measure: Levels of inflammatory cytokines/chemokines
time frame: From screening up to 24 weeks after first treatment administration
description: IL-6, TNFa, IP-10, MCP-1, sICAM, CXCL13
measure: DAS28 CRP
time frame: From screening to 24 weeks after first treatment administration
description: Measure of Disease Activity Scores (DAS) for Rheumatism in 28 tender or swollen joints and C-Reactive protein (CRP) - DAS28-CRP
measure: ACR criteria
time frame: From randomization to 24 weeks after first treatment administration
description: Proportion of patients achieving American College of Rheumatology Criteria (ACR20, ACR50 and ACR70)
measure: Proportion of patient achieving remission
time frame: From randomization to 24 weeks after first treatment administration
description: Proportion of patient achieving remission (defined as DAS28 < 2.6)
measure: EULAR response
time frame: From randomization to 24 weeks after first treatment administration
description: Proportion of patients achieving European League Against Rheumatism (EULAR) response criteria - good, moderate and no response
measure: Joint Count
time frame: From screening to 24 weeks after first treatment administration
description: Mean number of Tender Joint Count/Swollen Joint Count.
measure: SDAI score
time frame: From randomization to 24 weeks after first treatment administration
description: Mean improvement from baseline in Simplified Disease Activity Index (SDAI) score
measure: HAQ-DI score
time frame: From randomization to 24 weeks after first treatment administration
description: Mean improvement from baseline in the Health Assessment Questionnaire without Disability Index (HAQ-DI) score
measure: SF-36 score
time frame: from randomization to 24 weeks after first treatment administration
description: Mean improvement from baseline in 36-Item Short-Form Health Survey (SF-36) score
measure: DAS28-ESR
time frame: From screening to 24 weeks after first treatment administration
description: Measure of Disease Activity Scores (DAS) for Rheumatism in 28 tender or swollen joints and Erythrocyte Sedimentation Rate (ESR) levels - DAS28-ESR
measure: CDAI score
time frame: From randomization to 24 weeks after first treatment administration
description: Mean improvement from baseline in Clinical Disease Activity Index (CDAI) score scores
measure: Exploratory PK analysis - Cmax
time frame: From randomization to 24 weeks after first treatment administration
description: Peak drug plasma concentration (Cmax)
measure: Exploratory PK analysis - Tmax
time frame: From screening up to 24 weeks after first treatment administration
description: Time when plasma concentration is at peak (Tmax)
measure: Exploratory PK analysis - Ctrough
time frame: From randomization to 24 weeks after first treatment administration
description: Plasma drug concentration immediately prior next dosing (Ctrough)
measure: Exploratory PK analysis - AUC
time frame: From randomization to 24 weeks after first treatment administration
description: Area under the plasma concentration versus time curve (AUC)
measure: Exploratory PK analysis - CL
time frame: From randomization to 24 weeks after first treatment administration
description: Systemic drug clearance (CL)
arm group label: NI-0101
arm group type: Experimental
description: A therapeutic humanized monoclonal antibody, administered by intravenous infusion every 2 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: The placebo matches NI-0101 without active ingredient, administered by intravenous infusion every 2 weeks.
intervention type: Drug
intervention name: NI-0101
description: Humanized immunoglobulin gamma 1 (IgG1) kappa monoclonal antibody targeting TLR4
arm group label: NI-0101
intervention type: Other
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ernest Choy, MD
role: Principal Investigator
affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Bosnia and Herzegovina
country: Bulgaria
country: Georgia
country: Hungary
country: Moldova, Republic of
country: Poland
country: Serbia
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid