<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/NCT03227419</url>
  </required_header>
  <id_info>
    <org_study_id>RC-P0055</org_study_id>
    <nct_id>NCT03227419</nct_id>
  </id_info>
  <brief_title>Abatacept vs Tocilizumab for the Treatment of RA in TNF Alpha Inhibitor Inadequate Responders</brief_title>
  <acronym>SUNSTAR</acronym>
  <official_title>Abatacept Versus Tocilizumab by Subcutaneous Administration for the Treatment of Rheumatoid Arthritis in TNF Alpha Inhibitor Inadequate Responder Patients: A Randomized, Open-labeled, Superiority Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lille Catholic University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lille Catholic University</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>
      Rheumatoid arthritis (RA) is the most common inflammatory rheumatoid disease in France,&#xD;
      affecting 0.3% of the general population. Without effective treatment, the persistent&#xD;
      inflammation causes invalidating pain and joint destruction, leading to major functional&#xD;
      disability.&#xD;
&#xD;
      Biological agents have been proposed for patients with RA who have the most severe form of&#xD;
      the disease and that are inadequate responder patients to conventional synthetic&#xD;
      Disease-modifying antirheumatic drugs (csDMARDs). TNF inhibitors (TNFi) are historically&#xD;
      proposed as the first biological DAMRD for inadequate responder patients to csDMARDs. A&#xD;
      diverse therapeutic arsenal has become available in recent years with the development of&#xD;
      non-anti-TNFα drugs whose mechanisms of action are different from the classical TNFi. This&#xD;
      new biotherapy class includes tocilizumab and abatacept, two drugs recently available for&#xD;
      subcutaneous administration that enables ambulatory care for patients who would otherwise&#xD;
      require repeated in-hospital care.&#xD;
&#xD;
      The role of these new treatments in the therapeutic strategy has been emphasized by studies&#xD;
      that demonstrated their efficacy as first-line treatments. However, in clinical practice,&#xD;
      TNFi remain the most common first-line treatment for the majority of patients, non-anti-TNFα&#xD;
      biological agents being reserved for inadequate responder patients.&#xD;
&#xD;
      In second line, several studies have investigated therapeutic strategies for inadequate&#xD;
      responder patients to TNFi. Current data suggest that it could be wise to change the&#xD;
      therapeutic target after failure of a first-line treatment with TNFi.&#xD;
&#xD;
      Data about the comparative efficacy of different biologics proposed after failure of a&#xD;
      first-line treatment with TNFi are in progress. Meta-analyses from registries and academic&#xD;
      trials conducted in France and The Netherlands suggest that non-anti-TNFα agents would have&#xD;
      equivalent or superior efficacy compared with a second TNFi. This finding suggests clinicians&#xD;
      to switch for an alternate therapeutic target after failure of a first-line TNFi.&#xD;
&#xD;
      Data comparing different non-anti-TNFα biologics in inadequate responder patients to TNFi are&#xD;
      scare. Industrial trials have demonstrated sustained biological efficacy of non-anti-TNFα&#xD;
      biologics after failure of a TNFi. However, there is very little solid data on the direct&#xD;
      comparison between them.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rheumatoid arthritis (RA) is the most common inflammatory rheumatoid disease in France,&#xD;
      affecting 0.3% of the general population. Without effective treatment, the persistent&#xD;
      inflammation causes invalidating pain and joint destruction, leading to major functional&#xD;
      disability as well as progressive structural damage resulting in major joint deformity.&#xD;
&#xD;
      Biologic agents are taking on an increasingly important role in the management of patients&#xD;
      with an inadequate response to conventional synthetic disease modifying anti-rheumatic drugs&#xD;
      (csDMARDs).&#xD;
&#xD;
      Biological DMARD (bDMARD) therapy consists in the use of monoclonal antibodies or fusion&#xD;
      proteins, administered intravenously or subcutaneously. The earliest developed biologic&#xD;
      agents have been available for more than 15 years. Tumor necrosis factor alpha (TNFα), a&#xD;
      pro-inflammatory cytokine, was the first cytokine successfully targeted by a biologic agent&#xD;
      for RA treatment. TNF inhibitors (TNFi) are historically proposed as the first bDAMRD for&#xD;
      inadequate responder patients to csDMARDs. More recently non-anti-TNFα drugs have emerged,&#xD;
      with other biological targets such as interleukin-6 receptor (tocilizumab) or B- (rituximab)&#xD;
      and T-lymphocytes (abatacept) that are implicated in the inflammatory response. Initially&#xD;
      administered strictly intravenously, these drugs are now available in formulations adapted to&#xD;
      subcutaneous administration, which allows ambulatory care for patients who otherwise would&#xD;
      require repeated in-hospital care.&#xD;
&#xD;
      National and international guidelines, especially those issued in 2013 by the European League&#xD;
      Against Rheumatism (EULAR) and also in 2013 by the French Society of Rheumatology now&#xD;
      recommend first-line treatment not only with TNFi but also with non-anti-TNFα biologic&#xD;
      agents. However, in routine practice, most clinicians preferably prescribe TNFi for the&#xD;
      first-line regimen, reserving non-anti-TNFα drugs to TNFi inadequate responder patients.&#xD;
&#xD;
      There is a growing body of research focusing on first-line biologic agents but there is very&#xD;
      little solid data on the direct randomized comparison between them. Actually, all three of&#xD;
      the published studies have systematically compared a non-anti-TNFα biomedication versus TNFi&#xD;
      (one study with a blinded design and two open studies).&#xD;
&#xD;
      The therapeutic strategy that should be adapted after failure of a TNFi regimen has also been&#xD;
      investigated. Those studies favor non-anti-TNF drugs over an alternate TNFi.&#xD;
&#xD;
      There is adequate evidence of the efficacy of the different non-anti-TNFα biologic agents&#xD;
      versus placebo after TNFi failure. In other hands, industrial trials have not provided any&#xD;
      comparative data between drugs. An academic trial from The Netherlands using medico-economic&#xD;
      performance as the primary outcome found no difference in efficacy between abatacept and&#xD;
      rituximab (a non-anti-TNFα drug administered exclusively intravenously) after failure of a&#xD;
      TNFi. Meta-analyses using data from care networks have not reported any difference between&#xD;
      different non-anti-TNFα drugs after failure of a TNFi.&#xD;
&#xD;
      Data from national registries have provided interesting complementary information since in&#xD;
      everyday practice these agents are generally used after failure of at least one TNFi. The&#xD;
      Danish registry thus suggests that the therapeutic response would be better with tocilizumab&#xD;
      than with abatacept. This observation was confirmed by an analysis of French registries data&#xD;
      presented at the American College of Rheumatology (ACR) congress in November 2016 showing&#xD;
      that tocilizumab exhibits superiority for treatment persistence over 2 years. These results&#xD;
      were fully in agreement with the findings of the French ROC trial comparing intravenous&#xD;
      administration of a second anti-TNFα drug versus a non-anti-TNFα agent after failure of an&#xD;
      anti-TNFα drug that suggested a superiority of tocilizumab over abatacept in the subgroup of&#xD;
      patients given a non-anti-TNFα agent. A recent Bayesian network meta-analysis showed better&#xD;
      efficacy in the non-anti-TNFα groups for ACR20 in patients who responded insufficiently to an&#xD;
      anti-TNFα.&#xD;
&#xD;
      Subcutaneous formulations have been recently developed for both tocilizumab and abatacept.&#xD;
      Subcutaneous administration is important because it enables ambulatory care for a substantial&#xD;
      number of patients who to date are recurrently hospitalized in day-care units for their&#xD;
      intravenous infusions. Excepting specific situations, the subcutaneous formulation will be&#xD;
      favored for a large majority of patients because of economic as well as practical&#xD;
      considerations. Phase III trials have demonstrated the equivalence of the intravenous versus&#xD;
      subcutaneous routes of administration focusing on efficacy and tolerance. The subcutaneous&#xD;
      formulation is now also available for routine administration of both tocilizumab and&#xD;
      abatacept. Nevertheless, despite large-scale industrial trials on drug equivalence, data&#xD;
      issuing from clinical practice suggest a potential difference in the behavior of these two&#xD;
      formulations which needs to be explored. Rituximab is apart in the treatment strategy because&#xD;
      of its exclusive intravenous administration at spaced intervals and because it is used for&#xD;
      specific patient profiles (extra-articular involvement, history of neoplasia, rheumatoid&#xD;
      factor (RF) and anti-citrullinated protein antibody (ACPA) positivity). There is no&#xD;
      perspective for the development of a subcutaneous formulation of rituximab for RA patients.&#xD;
      Furthermore, the routine treatment schedule for rituximab (one-time injections at a mean&#xD;
      interval of 9 months) would compromise comparison, especially short-term comparison, with&#xD;
      other subcutaneous treatments.&#xD;
&#xD;
      These findings illustrate the need for a new multicentric, prospective, randomized trial&#xD;
      designed to demonstrate the superiority of tocilizumab over abatacept in patients exhibiting&#xD;
      inadequate response to a first anti-TNFα. A direct comparison of subcutaneous formulation is&#xD;
      the need for the promising route of administration for future ambulatory care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 22, 2018</start_date>
  <completion_date type="Anticipated">November 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2024</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>Prospective, multicentric, randomized, open-label, superiority trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline to 6 months of the Clinical Disease Activity Index (CDAI)</measure>
    <time_frame>6 months</time_frame>
    <description>The CDAI is a composite score combining clinical items only: Tender 28-joint count, Swollen 28-joint count, Patient Global Disease Activity (PGA), Evaluator&quot;s Global Disease Activity (EGA). This score provides a numerical assessment reflecting disease activity independently of cute phase reactants.&#xD;
It will be measured at baseline and 6 months after inclusion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of the disease activity score</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>DAS28-ESR and DAS28-CRP: the disease activity score (DAS) is a composite score providing a numerical assessment based on the tender and swollen joint counts, the PGA VAS and the selected acute phase reactant (ESR or CRP).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of the Clinical Disease Activity Index (CDAI)</measure>
    <time_frame>3 and 12 months</time_frame>
    <description>The CDAI is a composite score combining clinical items only: Tender 28-joint count, Swollen 28-joint count, Patient Global Disease Activity (PGA), Evaluator&quot;s Global Disease Activity (EGA). This score provides a numerical assessment reflecting disease activity independently of cute phase reactants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of the SDAI</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>the simple disease activity index (SDAI) is a composite score providing a numerical assessment based on the tender and swollen joint count, the PGAVAS, the EGA VAS, and CRP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in HAQ quality-of-life scores</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in SF-36 quality-of-life scores</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in disease self assessment</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>FLARE-RA score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Patient's Pain Assessment (PPA)</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in PGA visual analogic scale (VAS)</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients having achieved low disease activity</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>Low disease activity (LDA) is defined as DAS28-ESR&lt;3.2 (LDA-DAS28-ESR) and CDAI&lt;10 (LDA-CDAI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients in good or moderate EULAR therapeutic response</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>Good or moderate EULAR therapeutic response is defined as at least 0.6-point reduction in DAS28-ESR and final DAS28-ESR&lt;5.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving ACR20 response</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>ACR20 response correspond to a 20% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving ACR50 response</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>ACR50 responses correspond respectively to a 50% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients achieving ACR70 response</measure>
    <time_frame>3, 6 and 12 months</time_frame>
    <description>ACR70 response correspond respectively to a 70% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of treatment persistence</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of patients presenting at least one adverse events</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of treatment withdrawals for intolerance</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of treatment withdrawals for intolerance requiring in-hospital care</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of cardiovascular events</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of perturbation of the lipid profile</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of severe infection requiring in-hospital care</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of rescue medication use authorized by the protocol and treatment dose of patients achieving treatment persistence</measure>
    <time_frame>3, 6 and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in joint US-Doppler synovitis and Doppler hyperemia grade of the hands and wrists</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Sharp score in hands, wrists and feet X-Ray</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in vascular endothelial growth factor (VEGF) levels</measure>
    <time_frame>At 3 and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in immunoglobulin (quantitative assay)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in interleukin-6 serum levels</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">224</enrollment>
  <condition>Arthritis, Rheumatoid</condition>
  <arm_group>
    <arm_group_label>Tocilizumab Prefilled Syringe</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Market approval recommendations will be respected. Treatment should be started within 7 days of randomization.&#xD;
The treatment protocol has no specific provision for treatment adaptation. Treatment will be managed in compliance with the marketing approval recommendations and drug labeling described below.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Abatacept Prefilled Syringe</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Market approval recommendations will be respected. Treatment should be started within 7 days of randomization.&#xD;
The treatment protocol has no specific provision for treatment adaptation. Treatment will be managed in compliance with the marketing approval recommendations and drug labeling described below.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab Prefilled Syringe</intervention_name>
    <description>Treatment arm: tocilizumab (RoActemra®):&#xD;
162 mg weekly a schema for therapeutic adaptation with injection intervals determined according to transaminase levels or blood cell counts (neutropenia, thrombopenia) as recommended by Roche-Chugaï (see table below).</description>
    <arm_group_label>Tocilizumab Prefilled Syringe</arm_group_label>
    <other_name>RoActemra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abatacept Prefilled Syringe</intervention_name>
    <description>Treatment arm: abatacept (Orencia®)&#xD;
125 mg weekly after an initial dose of 500 mg (body weight &lt;60kg), 750 mg (body weight between 60 and 100 kg), or 1000 mg (body weight &gt;100 mg) 24 hours before the first subcutaneous injection.</description>
    <arm_group_label>Abatacept Prefilled Syringe</arm_group_label>
    <other_name>Orencia</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age &gt;18 years&#xD;
&#xD;
          -  RA according to the ACR/EULAR 2010 criteria&#xD;
&#xD;
          -  inadequate response to a subcutaneously administered first-line TNFi defined as&#xD;
             moderate to high disease activity (DAS28-ESR&gt;3.2 and CDAI&gt;10) after at least 3 months&#xD;
             of treatment with a TNFi&#xD;
&#xD;
          -  beneficiary of the French National Health Insurance Fund&#xD;
&#xD;
          -  signed informed consent form&#xD;
&#xD;
          -  for women of childbearing age: effective contraception during treatment period with&#xD;
             engagement to continue such contraception for 14 weeks after last administration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  counter-indication for one or other of the two drugs under study&#xD;
&#xD;
          -  prior failure of the TNFi due to intolerance&#xD;
&#xD;
          -  receiving ≥15 mg/day prednisone for more than 4 weeks&#xD;
&#xD;
          -  pregnant or nursing women&#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>Pascart Tristan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>GHICL</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Amélie Lansiaux, MD, PhD</last_name>
    <phone>03 20 22 52 69</phone>
    <phone_ext>+33</phone_ext>
    <email>lansiaux.amelie@ghicl.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jean-Jacques Vitagliano, PhD</last_name>
    <phone>03 20 22 57 51</phone>
    <email>vitagliano.jean-jacques@ghicl.net</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hôpital Saint-Philibert</name>
      <address>
        <city>Lomme</city>
        <state>Hauts De France</state>
        <zip>59462</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tristan Pascart, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Tristan Pascart, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Avicenne</name>
      <address>
        <city>Bobigny</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luca SEMERANO, MD</last_name>
    </contact>
    <investigator>
      <last_name>Luca SEMERANO, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Bordeaux</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marie-Elise TRUCHETET, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Christophe RICHEZ, MD</last_name>
    </contact_backup>
    <investigator>
      <last_name>Marie-Elise TRUCHETET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christophe RICHEZ, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nicolas POURSAC, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH de Boulogne-sur-Mer</name>
      <address>
        <city>Boulogne-sur-Mer</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Renaud DESBARBIEUX, MD</last_name>
    </contact>
    <investigator>
      <last_name>Renaud DESBARBIEUX, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ch Cahors</name>
      <address>
        <city>Cahors</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Slim LASSOUED, MD</last_name>
    </contact>
    <investigator>
      <last_name>Slim LASSOUED, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martin SOUBRIER, MD, Pr</last_name>
    </contact>
    <contact_backup>
      <last_name>Anne TOURNADRE, MD, Pr</last_name>
    </contact_backup>
    <investigator>
      <last_name>Martin SOUBRIER, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anne TOURNADRE, MD, Pr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marion COUDERC, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Grenoble Hôpital Sud</name>
      <address>
        <city>Grenoble</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Athan BAILLET, MD, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Athan BAILLET, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHD Vendée</name>
      <address>
        <city>La Roche-sur-Yon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Grégoire CORMIER, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Stéphane VARIN, MD</last_name>
    </contact_backup>
    <investigator>
      <last_name>Grégoire CORMIER, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Bicêtre</name>
      <address>
        <city>Le Kremlin-Bicêtre</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xavier MARIETTE, MD, Pr</last_name>
    </contact>
    <contact_backup>
      <last_name>Frédéric DESMOULINS, MD</last_name>
    </contact_backup>
    <investigator>
      <last_name>Xavier MARIETTE, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU de Lille</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>René-Marc FLIPO, MD, Pr</last_name>
    </contact>
    <investigator>
      <last_name>René-Marc FLIPO, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clinique Infirmerie Protestante de Lyon</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>André BASCH, MD</last_name>
    </contact>
    <investigator>
      <last_name>André BASCH, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Montpellier</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jacques MOREL, MD, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Jacques MOREL, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Nice</name>
      <address>
        <city>Nice</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Véronique BREUIL, MD, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Véronique BREUIL, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Bichat</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sébastien OTTAVIANI, MD</last_name>
    </contact>
    <investigator>
      <last_name>Sébastien OTTAVIANI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jérôme AVOUAC, MD, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Jérôme AVOUAC, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital de la Pitié-Salpêtrière</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bruno FAUTREL, MD, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Bruno FAUTREL, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Lariboisière</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pascal RICHETTE, MD, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Pascal RICHETTE, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Poitiers</name>
      <address>
        <city>Poitiers</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elisabeth GERVAIS, MD, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Elisabeth GERVAIS, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH René-Dubos</name>
      <address>
        <city>Pontoise</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Edouard PERTUISET, MD</last_name>
    </contact>
    <investigator>
      <last_name>Edouard PERTUISET, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Reims</name>
      <address>
        <city>Reims</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Hugues SALMON, MD</last_name>
    </contact>
    <investigator>
      <last_name>Jean-Hugues SALMON, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Rouen</name>
      <address>
        <city>Rouen</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivier VITTECOQ, MD, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Olivier VITTECOQ, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Saint-Etienne</name>
      <address>
        <city>Saint-Étienne</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hubert MAROTTE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Hubert MAROTTE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Saint-Etienne</name>
      <address>
        <city>Saint-Étienne</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hubert MAROTTE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Hubert MAROTTE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHRU de Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jacques-Eric GOTTENBERG, MD, Pr</last_name>
    </contact>
    <investigator>
      <last_name>Jacques-Eric GOTTENBERG, MD, Pr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Tours</name>
      <address>
        <city>Tours</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Isabelle GRIFFOUL, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Jessica RENE, MD</last_name>
    </contact_backup>
    <investigator>
      <last_name>Isabelle GRIFFOUL, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jessica RENE, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Guillermo CARVAJAL ALEGRIA, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Saloua MAMMOU-MRAGHINI, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CH de Valenciennes</name>
      <address>
        <city>Valenciennes</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xavier DEPREZ, MD</last_name>
    </contact>
    <investigator>
      <last_name>Xavier DEPREZ, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 19, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Abatacept</mesh_term>
  </intervention_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/NCT03227419
org study id: RC-P0055
nct id: NCT03227419
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Rheumatoid arthritis (RA) is the most common inflammatory rheumatoid disease in France,
      affecting 0.3% of the general population. Without effective treatment, the persistent
      inflammation causes invalidating pain and joint destruction, leading to major functional
      disability.

      Biological agents have been proposed for patients with RA who have the most severe form of
      the disease and that are inadequate responder patients to conventional synthetic
      Disease-modifying antirheumatic drugs (csDMARDs). TNF inhibitors (TNFi) are historically
      proposed as the first biological DAMRD for inadequate responder patients to csDMARDs. A
      diverse therapeutic arsenal has become available in recent years with the development of
      non-anti-TNFα drugs whose mechanisms of action are different from the classical TNFi. This
      new biotherapy class includes tocilizumab and abatacept, two drugs recently available for
      subcutaneous administration that enables ambulatory care for patients who would otherwise
      require repeated in-hospital care.

      The role of these new treatments in the therapeutic strategy has been emphasized by studies
      that demonstrated their efficacy as first-line treatments. However, in clinical practice,
      TNFi remain the most common first-line treatment for the majority of patients, non-anti-TNFα
      biological agents being reserved for inadequate responder patients.

      In second line, several studies have investigated therapeutic strategies for inadequate
      responder patients to TNFi. Current data suggest that it could be wise to change the
      therapeutic target after failure of a first-line treatment with TNFi.

      Data about the comparative efficacy of different biologics proposed after failure of a
      first-line treatment with TNFi are in progress. Meta-analyses from registries and academic
      trials conducted in France and The Netherlands suggest that non-anti-TNFα agents would have
      equivalent or superior efficacy compared with a second TNFi. This finding suggests clinicians
      to switch for an alternate therapeutic target after failure of a first-line TNFi.

      Data comparing different non-anti-TNFα biologics in inadequate responder patients to TNFi are
      scare. Industrial trials have demonstrated sustained biological efficacy of non-anti-TNFα
      biologics after failure of a TNFi. However, there is very little solid data on the direct
      comparison between them.
Rheumatoid arthritis (RA) is the most common inflammatory rheumatoid disease in France,
      affecting 0.3% of the general population. Without effective treatment, the persistent
      inflammation causes invalidating pain and joint destruction, leading to major functional
      disability as well as progressive structural damage resulting in major joint deformity.

      Biologic agents are taking on an increasingly important role in the management of patients
      with an inadequate response to conventional synthetic disease modifying anti-rheumatic drugs
      (csDMARDs).

      Biological DMARD (bDMARD) therapy consists in the use of monoclonal antibodies or fusion
      proteins, administered intravenously or subcutaneously. The earliest developed biologic
      agents have been available for more than 15 years. Tumor necrosis factor alpha (TNFα), a
      pro-inflammatory cytokine, was the first cytokine successfully targeted by a biologic agent
      for RA treatment. TNF inhibitors (TNFi) are historically proposed as the first bDAMRD for
      inadequate responder patients to csDMARDs. More recently non-anti-TNFα drugs have emerged,
      with other biological targets such as interleukin-6 receptor (tocilizumab) or B- (rituximab)
      and T-lymphocytes (abatacept) that are implicated in the inflammatory response. Initially
      administered strictly intravenously, these drugs are now available in formulations adapted to
      subcutaneous administration, which allows ambulatory care for patients who otherwise would
      require repeated in-hospital care.

      National and international guidelines, especially those issued in 2013 by the European League
      Against Rheumatism (EULAR) and also in 2013 by the French Society of Rheumatology now
      recommend first-line treatment not only with TNFi but also with non-anti-TNFα biologic
      agents. However, in routine practice, most clinicians preferably prescribe TNFi for the
      first-line regimen, reserving non-anti-TNFα drugs to TNFi inadequate responder patients.

      There is a growing body of research focusing on first-line biologic agents but there is very
      little solid data on the direct randomized comparison between them. Actually, all three of
      the published studies have systematically compared a non-anti-TNFα biomedication versus TNFi
      (one study with a blinded design and two open studies).

      The therapeutic strategy that should be adapted after failure of a TNFi regimen has also been
      investigated. Those studies favor non-anti-TNF drugs over an alternate TNFi.

      There is adequate evidence of the efficacy of the different non-anti-TNFα biologic agents
      versus placebo after TNFi failure. In other hands, industrial trials have not provided any
      comparative data between drugs. An academic trial from The Netherlands using medico-economic
      performance as the primary outcome found no difference in efficacy between abatacept and
      rituximab (a non-anti-TNFα drug administered exclusively intravenously) after failure of a
      TNFi. Meta-analyses using data from care networks have not reported any difference between
      different non-anti-TNFα drugs after failure of a TNFi.

      Data from national registries have provided interesting complementary information since in
      everyday practice these agents are generally used after failure of at least one TNFi. The
      Danish registry thus suggests that the therapeutic response would be better with tocilizumab
      than with abatacept. This observation was confirmed by an analysis of French registries data
      presented at the American College of Rheumatology (ACR) congress in November 2016 showing
      that tocilizumab exhibits superiority for treatment persistence over 2 years. These results
      were fully in agreement with the findings of the French ROC trial comparing intravenous
      administration of a second anti-TNFα drug versus a non-anti-TNFα agent after failure of an
      anti-TNFα drug that suggested a superiority of tocilizumab over abatacept in the subgroup of
      patients given a non-anti-TNFα agent. A recent Bayesian network meta-analysis showed better
      efficacy in the non-anti-TNFα groups for ACR20 in patients who responded insufficiently to an
      anti-TNFα.

      Subcutaneous formulations have been recently developed for both tocilizumab and abatacept.
      Subcutaneous administration is important because it enables ambulatory care for a substantial
      number of patients who to date are recurrently hospitalized in day-care units for their
      intravenous infusions. Excepting specific situations, the subcutaneous formulation will be
      favored for a large majority of patients because of economic as well as practical
      considerations. Phase III trials have demonstrated the equivalence of the intravenous versus
      subcutaneous routes of administration focusing on efficacy and tolerance. The subcutaneous
      formulation is now also available for routine administration of both tocilizumab and
      abatacept. Nevertheless, despite large-scale industrial trials on drug equivalence, data
      issuing from clinical practice suggest a potential difference in the behavior of these two
      formulations which needs to be explored. Rituximab is apart in the treatment strategy because
      of its exclusive intravenous administration at spaced intervals and because it is used for
      specific patient profiles (extra-articular involvement, history of neoplasia, rheumatoid
      factor (RF) and anti-citrullinated protein antibody (ACPA) positivity). There is no
      perspective for the development of a subcutaneous formulation of rituximab for RA patients.
      Furthermore, the routine treatment schedule for rituximab (one-time injections at a mean
      interval of 9 months) would compromise comparison, especially short-term comparison, with
      other subcutaneous treatments.

      These findings illustrate the need for a new multicentric, prospective, randomized trial
      designed to demonstrate the superiority of tocilizumab over abatacept in patients exhibiting
      inadequate response to a first anti-TNFα. A direct comparison of subcutaneous formulation is
      the need for the promising route of administration for future ambulatory care.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, multicentric, randomized, open-label, superiority trial.
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline to 6 months of the Clinical Disease Activity Index (CDAI)
time frame: 6 months
description: The CDAI is a composite score combining clinical items only: Tender 28-joint count, Swollen 28-joint count, Patient Global Disease Activity (PGA), Evaluator"s Global Disease Activity (EGA). This score provides a numerical assessment reflecting disease activity independently of cute phase reactants.
It will be measured at baseline and 6 months after inclusion
measure: Change from baseline of the disease activity score
time frame: 3, 6 and 12 months
description: DAS28-ESR and DAS28-CRP: the disease activity score (DAS) is a composite score providing a numerical assessment based on the tender and swollen joint counts, the PGA VAS and the selected acute phase reactant (ESR or CRP).
measure: Change from baseline of the Clinical Disease Activity Index (CDAI)
time frame: 3 and 12 months
description: The CDAI is a composite score combining clinical items only: Tender 28-joint count, Swollen 28-joint count, Patient Global Disease Activity (PGA), Evaluator"s Global Disease Activity (EGA). This score provides a numerical assessment reflecting disease activity independently of cute phase reactants.
measure: Change from baseline of the SDAI
time frame: 3, 6 and 12 months
description: the simple disease activity index (SDAI) is a composite score providing a numerical assessment based on the tender and swollen joint count, the PGAVAS, the EGA VAS, and CRP
measure: Change from baseline in HAQ quality-of-life scores
time frame: 3, 6 and 12 months
measure: Change from baseline in SF-36 quality-of-life scores
time frame: 3, 6 and 12 months
measure: Change from baseline in disease self assessment
time frame: 3, 6 and 12 months
description: FLARE-RA score
measure: Change from baseline in Patient's Pain Assessment (PPA)
time frame: 3, 6 and 12 months
measure: Change from baseline in PGA visual analogic scale (VAS)
time frame: 3, 6 and 12 months
measure: Proportion of patients having achieved low disease activity
time frame: 3, 6 and 12 months
description: Low disease activity (LDA) is defined as DAS28-ESR<3.2 (LDA-DAS28-ESR) and CDAI<10 (LDA-CDAI)
measure: Proportion of patients in good or moderate EULAR therapeutic response
time frame: 3, 6 and 12 months
description: Good or moderate EULAR therapeutic response is defined as at least 0.6-point reduction in DAS28-ESR and final DAS28-ESR<5.1
measure: Proportion of patients achieving ACR20 response
time frame: 3, 6 and 12 months
description: ACR20 response correspond to a 20% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant)
measure: Proportion of patients achieving ACR50 response
time frame: 3, 6 and 12 months
description: ACR50 responses correspond respectively to a 50% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant)
measure: Proportion of patients achieving ACR70 response
time frame: 3, 6 and 12 months
description: ACR70 response correspond respectively to a 70% improvement in the following parameters: number of tender joints; number of swollen joints; 3/5 complementary items (PPA VAS, PGA VAS, EGA VAS, self-administered functional status questionnaire, acute phase reactant)
measure: Rates of treatment persistence
time frame: 3, 6 and 12 months
measure: Rates of patients presenting at least one adverse events
time frame: 3, 6 and 12 months
measure: Rates of treatment withdrawals for intolerance
time frame: 3, 6 and 12 months
measure: Rates of treatment withdrawals for intolerance requiring in-hospital care
time frame: 3, 6 and 12 months
measure: Rates of cardiovascular events
time frame: 3, 6 and 12 months
measure: Rates of perturbation of the lipid profile
time frame: 3, 6 and 12 months
measure: Rates of severe infection requiring in-hospital care
time frame: 3, 6 and 12 months
measure: Rate of rescue medication use authorized by the protocol and treatment dose of patients achieving treatment persistence
time frame: 3, 6 and 12 months
measure: Changes in joint US-Doppler synovitis and Doppler hyperemia grade of the hands and wrists
time frame: 6 months
measure: Changes in Sharp score in hands, wrists and feet X-Ray
time frame: 12 months
measure: Change in vascular endothelial growth factor (VEGF) levels
time frame: At 3 and 6 months
measure: Changes in immunoglobulin (quantitative assay)
time frame: 6 months
measure: Changes in interleukin-6 serum levels
time frame: 6 months
arm group label: Tocilizumab Prefilled Syringe
arm group type: Experimental
description: Market approval recommendations will be respected. Treatment should be started within 7 days of randomization.
The treatment protocol has no specific provision for treatment adaptation. Treatment will be managed in compliance with the marketing approval recommendations and drug labeling described below.
arm group label: Abatacept Prefilled Syringe
arm group type: Experimental
description: Market approval recommendations will be respected. Treatment should be started within 7 days of randomization.
The treatment protocol has no specific provision for treatment adaptation. Treatment will be managed in compliance with the marketing approval recommendations and drug labeling described below.
intervention type: Drug
intervention name: Tocilizumab Prefilled Syringe
description: Treatment arm: tocilizumab (RoActemra®):
162 mg weekly a schema for therapeutic adaptation with injection intervals determined according to transaminase levels or blood cell counts (neutropenia, thrombopenia) as recommended by Roche-Chugaï (see table below).
arm group label: Tocilizumab Prefilled Syringe
other name: RoActemra
intervention type: Drug
intervention name: Abatacept Prefilled Syringe
description: Treatment arm: abatacept (Orencia®)
125 mg weekly after an initial dose of 500 mg (body weight <60kg), 750 mg (body weight between 60 and 100 kg), or 1000 mg (body weight >100 mg) 24 hours before the first subcutaneous injection.
arm group label: Abatacept Prefilled Syringe
other name: Orencia
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pascart Tristan, MD
role: Principal Investigator
affiliation: GHICL
last name: Amélie Lansiaux, MD, PhD
phone: 03 20 22 52 69
phone ext: +33
email: lansiaux.amelie@ghicl.net
last name: Jean-Jacques Vitagliano, PhD
phone: 03 20 22 57 51
email: vitagliano.jean-jacques@ghicl.net
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Abatacept
sharing ipd: No