<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/NCT04470453</url>
  </required_header>
  <id_info>
    <org_study_id>19CH114</org_study_id>
    <secondary_id>2019-003700-12</secondary_id>
    <nct_id>NCT04470453</nct_id>
  </id_info>
  <brief_title>Association Between Methotrexate Erythrocyte Polyglutamate Concentration and Biological Drug Concentration and Clinical Response in Rheumatoid Arthritis Patients Treated With Subcutaneous Injectable Methotrexate and a First Biological Drug</brief_title>
  <acronym>POLYbio</acronym>
  <official_title>Association Between Methotrexate Erythrocyte Polyglutamate Concentration and Biological Drug Concentration and Clinical Response in Rheumatoid Arthritis Patients Treated With Subcutaneous Injectable Methotrexate and a First Biological Drug</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Saint Etienne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Saint Etienne</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The combination of methotrexate (MTX) with a biological disease-modifying antirheumatic drugs&#xD;
      (bDMARD) is the next step in treatment with MTX monotherapy in rheumatoid arthritis (RA).&#xD;
      Estimation of MTX and bDMARD impregnation could be performed with the erythrocyte MTX&#xD;
      polyglutamate (MTX-PG) and bDMARD assays before to move to a second bDMARD. In RA patients&#xD;
      treated with MTX (prescribed for at least 6 months at a stable dose for at least 3 months) in&#xD;
      combination to a first bDMARD (prescribed since at least 3 months), an assay of MTX-PG and&#xD;
      bDMARD will be performed in tow subsets of RA according to the level of disease activity. The&#xD;
      first subset is active RA defined by a DAS28 (disease activity score 28)&gt;3.2. The second one&#xD;
      is RA in clinical remission defined by a DAS28&lt;2.6. The main hypothesis is the association&#xD;
      between the low concentration of MTX-PG and the clinical response of RA patients treated with&#xD;
      subcutaneous methotrexate injection associated to a first bDMARD. Adherence to MTX will be&#xD;
      reviewed by the Compliance Questionnaire Rheumatology (CQR) questionnaire. This assay could&#xD;
      be useful to improve MTX management before to move to a second bDMARD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 8, 2020</start_date>
  <completion_date type="Anticipated">January 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>MTX-PG concentration</measure>
    <time_frame>Hour 1</time_frame>
    <description>To compare MTX-PG concentration in patients with active rheumatoid arthritis and patients with rheumatoid arthritis in remission</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>metabolites dosing of MTX-PG (nmol/l)</measure>
    <time_frame>Hour 1</time_frame>
    <description>Analysis of different metabolites dosing of MTX-PG by High-performance liquid chromatography technical</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of CQR score response</measure>
    <time_frame>Hour 1</time_frame>
    <description>Compliance Rheumatology Questionnaire (CRQ) is a 19-item self-administered questionnaire to measure overall patient compliance for both MTX and bDMARD treatment with 0 (bad compliance) and 100 (better compliance).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Patients with active rheumatoid arthritis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 patients with active rheumatoid arthritis will be included. They will have a blood sample and Compliance Rheumatology Questionnaire (CRQ).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with rheumatoid arthritis into remission</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 patients with rheumatoid arthritis into remission will be included. They will have a blood sample and Compliance Rheumatology Questionnaire (CRQ).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Blood sample</intervention_name>
    <description>Blood samples will be collected for measuring PG-MTX blood concentration.</description>
    <arm_group_label>Patients with active rheumatoid arthritis</arm_group_label>
    <arm_group_label>Patients with rheumatoid arthritis into remission</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>CRQ</intervention_name>
    <description>Compliance Rheumatology Questionnaire (CQR) is a self-administered questionnaire for to evaluate therapeutic observance during rheumatoid arthritis.</description>
    <arm_group_label>Patients with active rheumatoid arthritis</arm_group_label>
    <arm_group_label>Patients with rheumatoid arthritis into remission</arm_group_label>
    <other_name>Compliance Rheumatology Questionnaire</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years and have social security affiliation.&#xD;
&#xD;
          -  Patients followed in the Rheumatology Department at the hospital of St Etienne.&#xD;
&#xD;
          -  Rheumatoid Arthritis patients in remission (Disease Activity Score 28&lt;2.6) with&#xD;
             methotrexate (MTX) treatment for at least 6months, and with a stable dose for 3months.&#xD;
&#xD;
          -  Patients with a High Disease Activity Rheumatoid Arthritis activity (Disease Activity&#xD;
             Score 28&gt;3.2) with methotrexate (MTX) treatment (≥ 15 mg/week), taking MTX treatment&#xD;
             for at least 6months with a stable subcutaneous weekly MTX injection (≥ 15 mg/week)&#xD;
             treatment during the previous 3 months.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients treated with another conventional synthetic Disease Modifying Anti-Rheumatic&#xD;
             Drugs (csDMARD)&#xD;
&#xD;
          -  Another diagnostic than rheumatoid arthritis&#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>Hubert MAROTTE, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU SAINT-ETIENNE</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hubert MAROTTE, MD PhD</last_name>
    <phone>(0)477127643</phone>
    <phone_ext>+33</phone_ext>
    <email>hubert.marotte@chu-st-etienne.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Florence RANCON, CRA</last_name>
    <phone>(0)477120284</phone>
    <phone_ext>+33</phone_ext>
    <email>florence.rancon@chu-st-etienne.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Chu Saint Etienne</name>
      <address>
        <city>Saint-Étienne</city>
        <zip>42055</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Hubert MAROTTE, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Thierry THOMAS, MD PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Béatrice PALLOT-PRADES, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Karima BOUSSOUALIM, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Adamah AMOUZOUGAN, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Astrid COASSY, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>April 25, 2023</last_update_submitted>
  <last_update_submitted_qc>April 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rheumatoid Arthritis</keyword>
  <keyword>Methotrexate</keyword>
  <keyword>Erythrocyte polyglutamate</keyword>
  <keyword>Compliance Questionnaire Rheumatology</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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04470453
org study id: 19CH114
secondary id: 2019-003700-12
nct id: NCT04470453
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The combination of methotrexate (MTX) with a biological disease-modifying antirheumatic drugs
      (bDMARD) is the next step in treatment with MTX monotherapy in rheumatoid arthritis (RA).
      Estimation of MTX and bDMARD impregnation could be performed with the erythrocyte MTX
      polyglutamate (MTX-PG) and bDMARD assays before to move to a second bDMARD. In RA patients
      treated with MTX (prescribed for at least 6 months at a stable dose for at least 3 months) in
      combination to a first bDMARD (prescribed since at least 3 months), an assay of MTX-PG and
      bDMARD will be performed in tow subsets of RA according to the level of disease activity. The
      first subset is active RA defined by a DAS28 (disease activity score 28)>3.2. The second one
      is RA in clinical remission defined by a DAS28<2.6. The main hypothesis is the association
      between the low concentration of MTX-PG and the clinical response of RA patients treated with
      subcutaneous methotrexate injection associated to a first bDMARD. Adherence to MTX will be
      reviewed by the Compliance Questionnaire Rheumatology (CQR) questionnaire. This assay could
      be useful to improve MTX management before to move to a second bDMARD.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MTX-PG concentration
time frame: Hour 1
description: To compare MTX-PG concentration in patients with active rheumatoid arthritis and patients with rheumatoid arthritis in remission
measure: metabolites dosing of MTX-PG (nmol/l)
time frame: Hour 1
description: Analysis of different metabolites dosing of MTX-PG by High-performance liquid chromatography technical
measure: Analysis of CQR score response
time frame: Hour 1
description: Compliance Rheumatology Questionnaire (CRQ) is a 19-item self-administered questionnaire to measure overall patient compliance for both MTX and bDMARD treatment with 0 (bad compliance) and 100 (better compliance).
arm group label: Patients with active rheumatoid arthritis
arm group type: Experimental
description: 30 patients with active rheumatoid arthritis will be included. They will have a blood sample and Compliance Rheumatology Questionnaire (CRQ).
arm group label: Patients with rheumatoid arthritis into remission
arm group type: Experimental
description: 30 patients with rheumatoid arthritis into remission will be included. They will have a blood sample and Compliance Rheumatology Questionnaire (CRQ).
intervention type: Biological
intervention name: Blood sample
description: Blood samples will be collected for measuring PG-MTX blood concentration.
arm group label: Patients with active rheumatoid arthritis
arm group label: Patients with rheumatoid arthritis into remission
intervention type: Diagnostic Test
intervention name: CRQ
description: Compliance Rheumatology Questionnaire (CQR) is a self-administered questionnaire for to evaluate therapeutic observance during rheumatoid arthritis.
arm group label: Patients with active rheumatoid arthritis
arm group label: Patients with rheumatoid arthritis into remission
other name: Compliance Rheumatology Questionnaire
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hubert MAROTTE, MD PhD
role: Principal Investigator
affiliation: CHU SAINT-ETIENNE
last name: Hubert MAROTTE, MD PhD
phone: (0)477127643
phone ext: +33
email: hubert.marotte@chu-st-etienne.fr
last name: Florence RANCON, CRA
phone: (0)477120284
phone ext: +33
email: florence.rancon@chu-st-etienne.fr
facility: 
status: Recruiting
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
sharing ipd: No