<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/NCT03016260</url>
  </required_header>
  <id_info>
    <org_study_id>2016-A00556-45</org_study_id>
    <nct_id>NCT03016260</nct_id>
  </id_info>
  <brief_title>RABIOPRED - a Validation Study of Theranostic Test to PREDict Treatment Response of Anti-TNFα BIologicals in Rheumatoid Arthritis</brief_title>
  <acronym>RABIOPRED</acronym>
  <official_title>Proof-of-Performance Study of RABIOPRED Assay as an In Vitro Diagnostic Test to Identify Patients With Rheumatoid Arthritis Who Are Unlikely to Show Response to 1st Treatment With Anti-TNFα and Methotrexate Combination.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>TcLand Expression S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Commission</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>TcLand Expression S.A.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      RABIOPRED is an in vitro non-invasive blood test, which aims to identify patients with&#xD;
      rheumatoid arthritis (RA) who are not likely to respond to anti-TNFα and methotrexate&#xD;
      combination therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multi-centre, non-interventional, open-label, non-comparative, prospective cohort study with&#xD;
      a clinical follow-up between (a) 12 and 14 weeks and (b) 22 and 24 weeks.&#xD;
&#xD;
      The RABIOPRED test is indicated for use in patients:&#xD;
&#xD;
        -  18 years of age or older,&#xD;
&#xD;
        -  Eligible for a first line biologic therapy with anti-TNF alpha. The RABIOPRED test is&#xD;
           indicated for use by rheumatologists as a biological basis for guiding anti-TNF alpha&#xD;
           treatment prior to its initiation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">December 20, 2019</completion_date>
  <primary_completion_date type="Actual">December 20, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>EULAR response criteria</measure>
    <time_frame>13th week (+/- 7 days)</time_frame>
    <description>Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on the EULAR (EUropean League Against Rheumatism) response criteria at 13th week (+/- 7 days) compared with baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ACR response criteria</measure>
    <time_frame>13th week (+/- 7 days)</time_frame>
    <description>Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on ACR (American College of Rheumatology) response criteria at 13th week (+/- 7 days) compared with baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EULAR response criteria</measure>
    <time_frame>23rd week (+/- 7 days) or at the time of treatment switch</time_frame>
    <description>Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on the EULAR (EUropean League Against Rheumatism) response criteria at 23rd week (+/- 7 days) or at the time of treatment switch (whichever comes first) compared with baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SDAI (Simplified Disease Activity Index) score</measure>
    <time_frame>23rd week (+/- 7 days) or at the time of treatment switch</time_frame>
    <description>Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on achieving Low Disease Activity (LDA) according to SDAI score at 23rd week (+/- 7 days) or at the time of treatment switch (whichever comes first) compared with baseline.</description>
  </secondary_outcome>
  <number_of_groups>8</number_of_groups>
  <enrollment type="Actual">250</enrollment>
  <condition>RheumatoId Arthritis</condition>
  <arm_group>
    <arm_group_label>Infliximab (Remicade®)</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Adalimumab (Humira®)</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Etanercept (Enbrel®)</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Golimumab (Simponi®)</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Certolizumab Pegol (Cimzia®)</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Infliximab biosimilar (Remsima®/ Inflectra®)</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Etanercept biosimilar (Benepali®)</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Infliximab biosimilar (Flixabi®)</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Infliximab</intervention_name>
    <description>Anti-TNF alpha originator</description>
    <arm_group_label>Infliximab (Remicade®)</arm_group_label>
    <other_name>Remicade®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Adalimumab</intervention_name>
    <description>Anti-TNF alpha originator</description>
    <arm_group_label>Adalimumab (Humira®)</arm_group_label>
    <other_name>Humira®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Etanercept</intervention_name>
    <description>Anti-TNF alpha originator</description>
    <arm_group_label>Etanercept (Enbrel®)</arm_group_label>
    <other_name>Enbrel®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Golimumab</intervention_name>
    <description>Anti-TNF alpha originator</description>
    <arm_group_label>Golimumab (Simponi®)</arm_group_label>
    <other_name>Simponi®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Certolizumab Pegol</intervention_name>
    <description>Anti-TNF alpha originator</description>
    <arm_group_label>Certolizumab Pegol (Cimzia®)</arm_group_label>
    <other_name>Cimzia®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Infliximab biosimilar</intervention_name>
    <description>Anti-TNF alpha Infliximab biosimilars</description>
    <arm_group_label>Infliximab biosimilar (Remsima®/ Inflectra®)</arm_group_label>
    <other_name>Remsima® or Inflectra®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Etanercept biosimilar</intervention_name>
    <description>Anti-TNF alpha Etanercept biosimilar</description>
    <arm_group_label>Etanercept biosimilar (Benepali®)</arm_group_label>
    <other_name>Benepali®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Infliximab biosimilar</intervention_name>
    <description>Anti-TNF alpha Infliximab biosimilar</description>
    <arm_group_label>Infliximab biosimilar (Flixabi®)</arm_group_label>
    <other_name>Flixabi®</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      DNA, RNA, Plasma, Serum, PBMC and Urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients suffering from rheumatoid arthritis eligible for biologic therapy, for whom the&#xD;
        rheumatologist envisages anyone of anti-TNFα, will be included in this study. As the study&#xD;
        should not modify patient care, it is not authorized to prescribe study biologics if other&#xD;
        biologic is considered for a given patient or if a given patient is not eligible for study&#xD;
        biologic treatment.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient with a confirmed Rheumatoid Arthritis according the American College of&#xD;
             Rheumatology (ACR) classification criteria (Arnett FC, 1988, Arthritis Rheum)&#xD;
&#xD;
          -  Patient with a DAS28 index greater than 3.2.&#xD;
&#xD;
          -  Patient eligible for treatment with an anti-TNFα agent (any one of Remicade®, Humira®,&#xD;
             Enbrel®, Simponi®, Cimzia®, Remsima®/Inflectra®, Benepali® and Flixabi® according to&#xD;
             the &quot;Summary of Product Characteristics&quot; for each product) and Methotrexate&#xD;
             combination therapy,&#xD;
&#xD;
          -  Patient refractory to treatment with at least one classical DMARDs (one of which has&#xD;
             to be MTX) prescribed according to the international recommendations, i.e. for at&#xD;
             least 12 weeks at the maximal tolerated dose prior to anti-TNFα treatment and with&#xD;
             doses which must have been kept stable during the 4 weeks preceding the initiation of&#xD;
             the anti-TNFα therapy. In case of Leflunomide treatment, patients may be included in&#xD;
             the study after a period of at least 3 months of Leflunomide stop, or after a washout&#xD;
             by cholestyramine for at least 11 days.&#xD;
&#xD;
          -  Use of oral steroids (≤ 10 mg/day of prednisone or equivalent dose of another&#xD;
             molecule) and/or NSAIDs will be permitted; doses must have been kept stable during the&#xD;
             4 weeks preceding the initiation of the anti-TNFα therapy&#xD;
&#xD;
          -  Patient (male or female) at 18 years of age or older at inclusion,&#xD;
&#xD;
          -  Negative β-HCG (Human Chorionic Gonadotrophin) pregnancy test, when appropriate,&#xD;
             according to the patient's age and contraceptive method.&#xD;
&#xD;
          -  Written Informed consent signed from the patient.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient having received previously any anti-TNFα biologic therapy or any molecule in&#xD;
             development belonging to anti-TNFα class. Patients having received other biologics&#xD;
             (such as anti-CD20, anti-CTLA4, IL1 blockers, IL6 blockers and other molecules in&#xD;
             development) can be included in the study after a period of at least 6 months,&#xD;
&#xD;
          -  Patient non eligible to anti-TNFα according to the SmPC (Summary of Products),&#xD;
&#xD;
          -  Patient on anti-TNFα monotherapy without methotrexate,&#xD;
&#xD;
          -  Patient with clinically significant, severe and uncontrolled infectious diseases,&#xD;
&#xD;
          -  Patient with symptoms of a significant somatic or psychiatric/mental illness,&#xD;
&#xD;
          -  Patient with other auto-immune diseases (i.e. Inflammatory Bowel Diseases, Systemic&#xD;
             Lupus Erythematosus, vasculitis, uncontrolled asthma, etc.),&#xD;
&#xD;
          -  Patient with evidence of cardiac, pulmonary, metabolic, renal, hepatic,&#xD;
             gastro-intestinal conditions, which, in the opinion of the Investigator, may interfere&#xD;
             with the study,&#xD;
&#xD;
          -  Cancer,&#xD;
&#xD;
          -  Pregnancy,&#xD;
&#xD;
          -  Nursing mothers,&#xD;
&#xD;
          -  Patient who is participating in a clinical trial of other biologics or for whom a&#xD;
             period of exclusion has been defined&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Institute of Rheumatology</name>
      <address>
        <city>Prague</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU-Montpellier</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nice</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Strasbourg Hautepierre</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tel Aviv Surasky Medical Center</name>
      <address>
        <city>Tel Aviv</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leiden University Medical Center</name>
      <address>
        <city>Leiden</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University</name>
      <address>
        <city>Istanbul</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Marmara</name>
      <address>
        <city>İstanbul</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
    <country>France</country>
    <country>Israel</country>
    <country>Netherlands</country>
    <country>Turkey</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 10, 2017</study_first_posted>
  <last_update_submitted>December 21, 2019</last_update_submitted>
  <last_update_submitted_qc>December 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rheumatoid Arthritis</keyword>
  <keyword>Anti TNF</keyword>
  <keyword>Infliximab</keyword>
  <keyword>Adalimumab</keyword>
  <keyword>Etanercept</keyword>
  <keyword>Golimumab</keyword>
  <keyword>Certolizumab Pegol</keyword>
  <keyword>Infliximab biosimilar</keyword>
  <keyword>Etanercept biosimilar</keyword>
  <keyword>Methotrexate</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>Adalimumab</mesh_term>
    <mesh_term>Infliximab</mesh_term>
    <mesh_term>Golimumab</mesh_term>
    <mesh_term>Certolizumab Pegol</mesh_term>
    <mesh_term>Etanercept</mesh_term>
  </intervention_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/NCT03016260
org study id: 2016-A00556-45
nct id: NCT03016260
lead sponsor: 
collaborator: 
has dmc: Yes
RABIOPRED is an in vitro non-invasive blood test, which aims to identify patients with
      rheumatoid arthritis (RA) who are not likely to respond to anti-TNFα and methotrexate
      combination therapy.
Multi-centre, non-interventional, open-label, non-comparative, prospective cohort study with
      a clinical follow-up between (a) 12 and 14 weeks and (b) 22 and 24 weeks.

      The RABIOPRED test is indicated for use in patients:

        -  18 years of age or older,

        -  Eligible for a first line biologic therapy with anti-TNF alpha. The RABIOPRED test is
           indicated for use by rheumatologists as a biological basis for guiding anti-TNF alpha
           treatment prior to its initiation.
observational model: Cohort
time perspective: Prospective
measure: EULAR response criteria
time frame: 13th week (+/- 7 days)
description: Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on the EULAR (EUropean League Against Rheumatism) response criteria at 13th week (+/- 7 days) compared with baseline.
measure: ACR response criteria
time frame: 13th week (+/- 7 days)
description: Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on ACR (American College of Rheumatology) response criteria at 13th week (+/- 7 days) compared with baseline.
measure: EULAR response criteria
time frame: 23rd week (+/- 7 days) or at the time of treatment switch
description: Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on the EULAR (EUropean League Against Rheumatism) response criteria at 23rd week (+/- 7 days) or at the time of treatment switch (whichever comes first) compared with baseline.
measure: SDAI (Simplified Disease Activity Index) score
time frame: 23rd week (+/- 7 days) or at the time of treatment switch
description: Performance of RABIOPRED test to predict treatment response of anti-TNFα agents based on achieving Low Disease Activity (LDA) according to SDAI score at 23rd week (+/- 7 days) or at the time of treatment switch (whichever comes first) compared with baseline.
arm group label: Infliximab (Remicade®)
arm group label: Adalimumab (Humira®)
arm group label: Etanercept (Enbrel®)
arm group label: Golimumab (Simponi®)
arm group label: Certolizumab Pegol (Cimzia®)
arm group label: Infliximab biosimilar (Remsima®/ Inflectra®)
arm group label: Etanercept biosimilar (Benepali®)
arm group label: Infliximab biosimilar (Flixabi®)
intervention type: Biological
intervention name: Infliximab
description: Anti-TNF alpha originator
arm group label: Infliximab (Remicade®)
other name: Remicade®
intervention type: Biological
intervention name: Adalimumab
description: Anti-TNF alpha originator
arm group label: Adalimumab (Humira®)
other name: Humira®
intervention type: Biological
intervention name: Etanercept
description: Anti-TNF alpha originator
arm group label: Etanercept (Enbrel®)
other name: Enbrel®
intervention type: Biological
intervention name: Golimumab
description: Anti-TNF alpha originator
arm group label: Golimumab (Simponi®)
other name: Simponi®
intervention type: Biological
intervention name: Certolizumab Pegol
description: Anti-TNF alpha originator
arm group label: Certolizumab Pegol (Cimzia®)
other name: Cimzia®
intervention type: Biological
intervention name: Infliximab biosimilar
description: Anti-TNF alpha Infliximab biosimilars
arm group label: Infliximab biosimilar (Remsima®/ Inflectra®)
other name: Remsima® or Inflectra®
intervention type: Biological
intervention name: Etanercept biosimilar
description: Anti-TNF alpha Etanercept biosimilar
arm group label: Etanercept biosimilar (Benepali®)
other name: Benepali®
intervention type: Biological
intervention name: Infliximab biosimilar
description: Anti-TNF alpha Infliximab biosimilar
arm group label: Infliximab biosimilar (Flixabi®)
other name: Flixabi®
DNA, RNA, Plasma, Serum, PBMC and Urine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Czechia
country: France
country: Israel
country: Netherlands
country: Turkey
country: Czech Republic
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Adalimumab
mesh term: Infliximab
mesh term: Golimumab
mesh term: Certolizumab Pegol
mesh term: Etanercept