<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/NCT02990286</url>
  </required_header>
  <id_info>
    <org_study_id>PHRN15-SMA/EvER-ILD</org_study_id>
    <nct_id>NCT02990286</nct_id>
  </id_info>
  <brief_title>Evaluation of Efficacy and Safety of Rituximab With Mycophenolate Mofetil in Patients With Interstitial Lung Diseases</brief_title>
  <acronym>EvER-ILD</acronym>
  <official_title>Evaluation of Efficacy and Safety of Rituximab in Association With Mycophenolate Mofetil Versus Mycophenolate Mofetil Alone in Patients With Interstitial Lung Diseases (ILD) Non-responders to a First-line Immunosuppressive Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Tours</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Tours</source>
  <oversight_info>
    <has_dmc>Yes</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 purpose of the study is to evaluate the efficacy on lung function 6 months after one&#xD;
      course of rituximab (2 infusions) and mycophénolate mofétil (MMF) treatment compared to one&#xD;
      course of placebo and 6 months of MMF treatment in a broad range of patients with&#xD;
      Interstitial Lung Diseases (ILD) non-responders to a first line immunosuppressive treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 20, 2017</start_date>
  <completion_date type="Actual">February 17, 2020</completion_date>
  <primary_completion_date type="Actual">July 24, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in FVC in % of predicted</measure>
    <time_frame>From baseline to 6 months</time_frame>
    <description>Change in FVC (in % of predicted) since declines in FVC correlates with increased risk of subsequent mortality in ILD patients and FVC is one of the core set of outcomes defined in interstitial lung diseases. Data obtained from the two groups of patients (rituximab and placebo) will be compared to each other. FVC will be performed in each study center in a standardized manner according to the ATS/ERS recommendations and ECCS reference equations</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS).</measure>
    <time_frame>PFS measured at 3, 6 and 12 months</time_frame>
    <description>PFS is defined as the time 1) to the first acute exacerbation, or 2) to an absolute decline of 10 % points in the percentage of the predicted FVC, or 3) to the necessity to withdraw the MMF with/without a new immunosuppressive treatment (except corticoids), or 4) to death or 5) registration to a lung transplantation list. An acute exacerbation is defined by (1) progressive dyspnea over 1 month or less; (2) new pulmonary infiltrates on chest radiography or computed tomography, and (3) the absence of an overt underlying cause of rapid deterioration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the quality of life score</measure>
    <time_frame>Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough</time_frame>
    <description>The quality of life score as measured by the SF-36 v1.3 questionnaire, version developed and validated in interstitial lung disease (ILD) patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the visual analogic scales of dyspnea</measure>
    <time_frame>Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough</time_frame>
    <description>Changes in the visual analogic scales of dyspnea (EVA test)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cough evaluation</measure>
    <time_frame>Changes from baseline to 6 months in cough evaluation</time_frame>
    <description>Changes in cough evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative doses of corticoids for the 2 groups</measure>
    <time_frame>Cumulative doses of corticoids at 6 months</time_frame>
    <description>Cumulative doses of corticoids for the 2 groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the FVC expressed as % of predicted</measure>
    <time_frame>Changes from baseline to 3 and 6 months in the FVC expressed as % of predicted</time_frame>
    <description>Changes in the FVC expressed as % of predicted</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in DLCO</measure>
    <time_frame>Changes from baseline to 6 months in DLCO</time_frame>
    <description>Changes in DLCO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the 6-minutes-walk test</measure>
    <time_frame>Changes from baseline to 6 months in the 6-minutes-walk test</time_frame>
    <description>Changes in the 6-minutes-walk test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in autoantibodies concentration</measure>
    <time_frame>Changes from baseline to 6 months in autoantibodies concentration</time_frame>
    <description>Changes in autoantibodies concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in biological markers related to lymphocyte B depletion: CD19 lymphocytes</measure>
    <time_frame>Changes from baseline to 6 months in lymphocytes B CD19</time_frame>
    <description>Changes in biological markers related to lymphocyte B depletion: CD19 lymphocytes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in gammaglobulins</measure>
    <time_frame>Changes from baseline to 6 months in gammaglobulins</time_frame>
    <description>Changes in gammaglobulins</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in HRCT of the chest images</measure>
    <time_frame>Changes from baseline to 6 months in HRCT of the chest images</time_frame>
    <description>Changes in HRCT of the chest images</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events related to treatment</measure>
    <time_frame>Adverse events during the 6 months of study period</time_frame>
    <description>In particular infectious adverse events and biological blood disorders during the 6 months of study period will be collected</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rituximab PK parameters : distribution volume</measure>
    <time_frame>Points at Day1, Day15, 3 and 6 months</time_frame>
    <description>Rituximab PK parameters : distribution volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rituximab clearance</measure>
    <time_frame>Points at Day1, Day15, 3 and 6 months</time_frame>
    <description>Rituximab clearance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life of rituximab in blood</measure>
    <time_frame>Points at Day1, Day15, 3 and 6 months</time_frame>
    <description>Half-life of rituximab in blood</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">122</enrollment>
  <condition>Lung Disease, Interstitial</condition>
  <arm_group>
    <arm_group_label>Rituximab with Mycophenolate Mofetil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo of rituximab with Mycophenolate Mofetil</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Rituximab 500mg concentrate for solution for infusion. One course of IV rituximab consisting of a first infusion of 1000 mg (500 ml solution) rituximab (day 1 infusion), and a second infusion of 1000 mg (500 ml solution) rituximab two weeks later (day 15 infusion)</description>
    <arm_group_label>Rituximab with Mycophenolate Mofetil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo of Rituximab</intervention_name>
    <description>500 ml of saline (0.9% sodium chloride) for infusion One course of intravenous placebo of rituximab consisting of a first infusion of 500 ml of saline (0.9% sodium chloride) infusion (day 1 infusion), and a second infusion of 500 ml of saline infusion two weeks later (day 15 infusion)</description>
    <arm_group_label>Placebo of rituximab with Mycophenolate Mofetil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate Mofetil</intervention_name>
    <description>Mycophenolate Mofetil 500mg film-coated tablets&#xD;
1 gram twice daily on oral route of MMF (= 2 grams daily) for 6 months.</description>
    <arm_group_label>Placebo of rituximab with Mycophenolate Mofetil</arm_group_label>
    <arm_group_label>Rituximab with Mycophenolate Mofetil</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years&#xD;
&#xD;
          2. A diagnosis of ILD:&#xD;
&#xD;
               -  ILD associated with differentiated CTD or IPAF (based on internationally accepted&#xD;
                  criteria)&#xD;
&#xD;
               -  OR idiopathic ILD&#xD;
&#xD;
          3. A diagnosis of NSIP based on:&#xD;
&#xD;
               -  a histological pattern of NSIP&#xD;
&#xD;
               -  OR HRCT findings suggestive of NSIP defined as basal predominant reticular&#xD;
                  abnormalities with traction bronchiectasis, peri-bronchovascular extension and&#xD;
                  subpleural sparing, frequently associated with ground-glass attenuation&#xD;
&#xD;
          4. Patients who did not respond or relapsed or were not able to continue at least one&#xD;
             first-line immunosuppressive treatment of ILD: corticosteroids, azathioprine,&#xD;
             cyclophosphamide or other immunosuppressants. For the assessment of clinical response,&#xD;
             the absence of response was defined as: either a decrease or an increase, but &lt;10% in&#xD;
             % predicted FVC.&#xD;
&#xD;
          5. Subjects covered by or having the rights to French social security (including CMU),&#xD;
&#xD;
          6. Written informed consent obtained from subject, with a specific check box on the&#xD;
             Consent form of the study, understanding the risk for men and women treated with&#xD;
             mycophenolate mofetil. And additional written consent from subject on the care and&#xD;
             contraception agreement form for women of childbearing potential treated with&#xD;
             mycophenolate.&#xD;
&#xD;
          7. Ability for subject to comply with the requirements of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known diagnosis of significant respiratory disorders (asthma, tuberculosis,&#xD;
             sarcoidosis, aspergillosis, or cystic fibrosis) other than CTD-NSIP, IPAF-NSIP and&#xD;
             iNSIP&#xD;
&#xD;
          2. Evidence of any clinically significant, severe or unstable, acute or chronically&#xD;
             progressive cardiac (severe heart failure New York Heart Association Class IV or&#xD;
             severe uncontrolled cardiac disease), other medical disease (other than NSIP) or&#xD;
             surgical disorder, or any condition that may affect patient safety in the judgment of&#xD;
             the investigator.&#xD;
&#xD;
          3. HRCT pattern of typical usual interstitial pneumonia (UIP)&#xD;
&#xD;
          4. For patients with idiopathic ILD, HRCT pattern of possible UIP (no evocative of NSIP)&#xD;
&#xD;
          5. Histological pattern other than pattern of NSIP&#xD;
&#xD;
          6. A first line treatment with MMF or rituximab&#xD;
&#xD;
          7. Known hypersensitivity to MMF or rituximab or sulfonamide antibiotics&#xD;
&#xD;
          8. Treatment with immunosuppressive treatments other than corticosteroids:&#xD;
&#xD;
               -  azathioprine, cyclophosphamide, methotrexate, cyclosporine, tacrolimus,&#xD;
                  leflunomide within 2 weeks (5 half-lives &lt;= 2 weeks) prior to inclusion&#xD;
&#xD;
               -  intravenous immunoglobulins, hydroxychloroquine or other monoclonal antibody&#xD;
                  therapies (such as but not limited to etanercept, adalimumab, efalizumab,&#xD;
                  infliximab, golimumab, certolizumab) within 6 months (5 half-lives &lt;= 6 months)&#xD;
                  prior to inclusion&#xD;
&#xD;
          9. Patients registered on a pulmonary transplantation list&#xD;
&#xD;
         10. Patients with known hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) hereditary&#xD;
             deficiency (such as Lesch-Nyhan and Kelley-Seegmiller syndrome)&#xD;
&#xD;
         11. Pregnant or breastfeeding women, or women of child-bearing potential not using two&#xD;
             reliable contraceptive methods (including female partners of sexually active men&#xD;
             treated with mycophenolate) and men not using a contraceptive method (condom), or&#xD;
             women and men having a pregnancy project during the year following randomization.&#xD;
&#xD;
         12. Patients at significant risk for infectious complications: HIV positive, other known&#xD;
             immunodeficiency syndromes, untreated tuberculosis, hepatitis B and C or other known&#xD;
             viral infection, infection requiring anti-infectious treatment in the preceding 4&#xD;
             weeks&#xD;
&#xD;
         13. Current history of substance and/or alcohol abuse&#xD;
&#xD;
         14. Deprivation of liberty, under judicial protection&#xD;
&#xD;
         15. Participation in another biomedical research with experimental drug or medical device&#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>TRACLET Julie</last_name>
    <role>Principal Investigator</role>
    <affiliation>HC LYON</affiliation>
  </overall_official>
  <overall_official>
    <last_name>NUNES Hilario</last_name>
    <role>Principal Investigator</role>
    <affiliation>AP-HP - Hôpital Avicenne</affiliation>
  </overall_official>
  <overall_official>
    <last_name>CRESTANI Bruno</last_name>
    <role>Principal Investigator</role>
    <affiliation>AP-HP - Hôpital Bichat</affiliation>
  </overall_official>
  <overall_official>
    <last_name>ISRAEL BIET Dominique</last_name>
    <role>Principal Investigator</role>
    <affiliation>AP-HP HEGP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>NACCACHE Jean-Marc</last_name>
    <role>Principal Investigator</role>
    <affiliation>AP-HP - Hôpital Tenon</affiliation>
  </overall_official>
  <overall_official>
    <last_name>WEMEAU Lidwine</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHRU LILLE</affiliation>
  </overall_official>
  <overall_official>
    <last_name>JOUNEAU Stéphane</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Rennes</affiliation>
  </overall_official>
  <overall_official>
    <last_name>PREVOT Grégoire</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Toulouse</affiliation>
  </overall_official>
  <overall_official>
    <last_name>REYNAUD-GAUBERT Martine</last_name>
    <role>Principal Investigator</role>
    <affiliation>AP-HM Hôpital Nord</affiliation>
  </overall_official>
  <overall_official>
    <last_name>HIRSCHI SANTELMO Sandrine</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHRU Strasbourg</affiliation>
  </overall_official>
  <overall_official>
    <last_name>GONDOUIN Anne</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier Universitaire de Besancon</affiliation>
  </overall_official>
  <overall_official>
    <last_name>COURT-FORTUNE Isabelle</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU ST-ETIENNE</affiliation>
  </overall_official>
  <overall_official>
    <last_name>BONNIAUD Philippe</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU DIJON</affiliation>
  </overall_official>
  <overall_official>
    <last_name>QUETANT Sébastien</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Grenoble</affiliation>
  </overall_official>
  <overall_official>
    <last_name>GOMEZ Emmanuel</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU NANCY</affiliation>
  </overall_official>
  <overall_official>
    <last_name>BLANC François-Xavier</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Nantes</affiliation>
  </overall_official>
  <overall_official>
    <last_name>MARQUETTE Charles-Hugo</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU NICE</affiliation>
  </overall_official>
  <overall_official>
    <last_name>MARCHAND-ADAM Sylvain</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHRU TOURS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chu Besancon</name>
      <address>
        <city>Besancon</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Dijon</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HM Hôpital NORD</name>
      <address>
        <city>Marseille</city>
        <zip>13015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Rennes</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Tours</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>November 25, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <last_update_submitted>November 3, 2020</last_update_submitted>
  <last_update_submitted_qc>November 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non specific intertitial pneumonia</keyword>
  <keyword>interstitial pneumonia with autoimmune feature</keyword>
  <keyword>connective tissue disease</keyword>
  <keyword>rituximab</keyword>
  <keyword>Mycophenolate Mofetil</keyword>
  <keyword>pulmonary fibrosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Interstitial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Rituximab</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/NCT02990286
org study id: PHRN15-SMA/EvER-ILD
nct id: NCT02990286
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of the study is to evaluate the efficacy on lung function 6 months after one
      course of rituximab (2 infusions) and mycophénolate mofétil (MMF) treatment compared to one
      course of placebo and 6 months of MMF treatment in a broad range of patients with
      Interstitial Lung Diseases (ILD) non-responders to a first line immunosuppressive treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in FVC in % of predicted
time frame: From baseline to 6 months
description: Change in FVC (in % of predicted) since declines in FVC correlates with increased risk of subsequent mortality in ILD patients and FVC is one of the core set of outcomes defined in interstitial lung diseases. Data obtained from the two groups of patients (rituximab and placebo) will be compared to each other. FVC will be performed in each study center in a standardized manner according to the ATS/ERS recommendations and ECCS reference equations
measure: Progression Free Survival (PFS).
time frame: PFS measured at 3, 6 and 12 months
description: PFS is defined as the time 1) to the first acute exacerbation, or 2) to an absolute decline of 10 % points in the percentage of the predicted FVC, or 3) to the necessity to withdraw the MMF with/without a new immunosuppressive treatment (except corticoids), or 4) to death or 5) registration to a lung transplantation list. An acute exacerbation is defined by (1) progressive dyspnea over 1 month or less; (2) new pulmonary infiltrates on chest radiography or computed tomography, and (3) the absence of an overt underlying cause of rapid deterioration
measure: Changes in the quality of life score
time frame: Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough
description: The quality of life score as measured by the SF-36 v1.3 questionnaire, version developed and validated in interstitial lung disease (ILD) patients.
measure: Changes in the visual analogic scales of dyspnea
time frame: Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough
description: Changes in the visual analogic scales of dyspnea (EVA test)
measure: Cough evaluation
time frame: Changes from baseline to 6 months in cough evaluation
description: Changes in cough evaluation
measure: Cumulative doses of corticoids for the 2 groups
time frame: Cumulative doses of corticoids at 6 months
description: Cumulative doses of corticoids for the 2 groups
measure: Changes in the FVC expressed as % of predicted
time frame: Changes from baseline to 3 and 6 months in the FVC expressed as % of predicted
description: Changes in the FVC expressed as % of predicted
measure: Changes in DLCO
time frame: Changes from baseline to 6 months in DLCO
description: Changes in DLCO
measure: Changes in the 6-minutes-walk test
time frame: Changes from baseline to 6 months in the 6-minutes-walk test
description: Changes in the 6-minutes-walk test
measure: Changes in autoantibodies concentration
time frame: Changes from baseline to 6 months in autoantibodies concentration
description: Changes in autoantibodies concentration
measure: Changes in biological markers related to lymphocyte B depletion: CD19 lymphocytes
time frame: Changes from baseline to 6 months in lymphocytes B CD19
description: Changes in biological markers related to lymphocyte B depletion: CD19 lymphocytes
measure: Changes in gammaglobulins
time frame: Changes from baseline to 6 months in gammaglobulins
description: Changes in gammaglobulins
measure: Changes in HRCT of the chest images
time frame: Changes from baseline to 6 months in HRCT of the chest images
description: Changes in HRCT of the chest images
measure: Adverse events related to treatment
time frame: Adverse events during the 6 months of study period
description: In particular infectious adverse events and biological blood disorders during the 6 months of study period will be collected
measure: Rituximab PK parameters : distribution volume
time frame: Points at Day1, Day15, 3 and 6 months
description: Rituximab PK parameters : distribution volume
measure: Rituximab clearance
time frame: Points at Day1, Day15, 3 and 6 months
description: Rituximab clearance
measure: Half-life of rituximab in blood
time frame: Points at Day1, Day15, 3 and 6 months
description: Half-life of rituximab in blood
arm group label: Rituximab with Mycophenolate Mofetil
arm group type: Experimental
arm group label: Placebo of rituximab with Mycophenolate Mofetil
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Rituximab
description: Rituximab 500mg concentrate for solution for infusion. One course of IV rituximab consisting of a first infusion of 1000 mg (500 ml solution) rituximab (day 1 infusion), and a second infusion of 1000 mg (500 ml solution) rituximab two weeks later (day 15 infusion)
arm group label: Rituximab with Mycophenolate Mofetil
intervention type: Drug
intervention name: Placebo of Rituximab
description: 500 ml of saline (0.9% sodium chloride) for infusion One course of intravenous placebo of rituximab consisting of a first infusion of 500 ml of saline (0.9% sodium chloride) infusion (day 1 infusion), and a second infusion of 500 ml of saline infusion two weeks later (day 15 infusion)
arm group label: Placebo of rituximab with Mycophenolate Mofetil
intervention type: Drug
intervention name: Mycophenolate Mofetil
description: Mycophenolate Mofetil 500mg film-coated tablets
1 gram twice daily on oral route of MMF (= 2 grams daily) for 6 months.
arm group label: Placebo of rituximab with Mycophenolate Mofetil
arm group label: Rituximab with Mycophenolate Mofetil
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: TRACLET Julie
role: Principal Investigator
affiliation: HC LYON
last name: NUNES Hilario
role: Principal Investigator
affiliation: AP-HP - Hôpital Avicenne
last name: CRESTANI Bruno
role: Principal Investigator
affiliation: AP-HP - Hôpital Bichat
last name: ISRAEL BIET Dominique
role: Principal Investigator
affiliation: AP-HP HEGP
last name: NACCACHE Jean-Marc
role: Principal Investigator
affiliation: AP-HP - Hôpital Tenon
last name: WEMEAU Lidwine
role: Principal Investigator
affiliation: CHRU LILLE
last name: JOUNEAU Stéphane
role: Principal Investigator
affiliation: CHU Rennes
last name: PREVOT Grégoire
role: Principal Investigator
affiliation: CHU Toulouse
last name: REYNAUD-GAUBERT Martine
role: Principal Investigator
affiliation: AP-HM Hôpital Nord
last name: HIRSCHI SANTELMO Sandrine
role: Principal Investigator
affiliation: CHRU Strasbourg
last name: GONDOUIN Anne
role: Principal Investigator
affiliation: Centre Hospitalier Universitaire de Besancon
last name: COURT-FORTUNE Isabelle
role: Principal Investigator
affiliation: CHU ST-ETIENNE
last name: BONNIAUD Philippe
role: Principal Investigator
affiliation: CHU DIJON
last name: QUETANT Sébastien
role: Principal Investigator
affiliation: University Hospital, Grenoble
last name: GOMEZ Emmanuel
role: Principal Investigator
affiliation: CHU NANCY
last name: BLANC François-Xavier
role: Principal Investigator
affiliation: CHU Nantes
last name: MARQUETTE Charles-Hugo
role: Principal Investigator
affiliation: CHU NICE
last name: MARCHAND-ADAM Sylvain
role: Principal Investigator
affiliation: CHRU TOURS
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Interstitial
mesh term: Mycophenolic Acid
mesh term: Rituximab
sharing ipd: No