<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/NCT04472169</url>
  </required_header>
  <id_info>
    <org_study_id>2019_75</org_study_id>
    <secondary_id>2020-A00584-35</secondary_id>
    <nct_id>NCT04472169</nct_id>
  </id_info>
  <brief_title>UPLC-MS/MS Monitoring of Emicizumab Therapy</brief_title>
  <acronym>EMICARE</acronym>
  <official_title>Value of Emicizumab Monitoring With UPLC-MS/MS for Bleeding Risk Prediction in Severe Hemophilia A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Groupement Interrégional de Recherche Clinique et d'Innovation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Lille</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>
      Emicizumab is a monoclonal bispecific antibody with a terminal half-life of 28 days which is&#xD;
      now licensed in the treatment of severe haemophilia A with or without inhibitors. Some&#xD;
      heterogeneity in residual emicizumab concentrations have been reported according to age, body&#xD;
      mass index or drug therapeutic regimen. Some cases of neutralizing antidrug antibodies have&#xD;
      been also reported. Whether monitoring emicizumab plasma concentration could predict the&#xD;
      residual bleeding risk under emicizumab is unknown. As conventional coagulation assays are&#xD;
      not adapted for emicizumab monitoring, this study aims to assess the value of monitoring&#xD;
      residual emicizumab plasma concentration by UPLC-MS/MS in bleeding risk prediction.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 13, 2022</start_date>
  <completion_date type="Anticipated">February 2024</completion_date>
  <primary_completion_date type="Anticipated">February 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the curve ROC of Residual plasma level of emicizumab</measure>
    <time_frame>At Week 5 (end of emicizumab loading period)</time_frame>
    <description>At least one clinically significant bleeding (defined as any bleeding treated with FVIII, rFVIIa or aPCC) from loading period completion (week 5) to the end of study, an average of 1 year</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Residual plasma level of emicizumab measured by UPLC-MS/MS</measure>
    <time_frame>At Week 5 (end of emicizumab loading period)</time_frame>
    <description>At least one hemarthrosis from loading period completion (week 5) to the end of study, an average of 1 year</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Residual plasma level of emicizumab measured by UPLC-MS/MS</measure>
    <time_frame>At each breakthrough bleeding until end of study</time_frame>
    <description>Post-traumatic or spontaneous nature of bleeding event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Residual plasma level of emicizumab (UPLC-MS/MS dosing)</measure>
    <time_frame>At Week 5 and at each breakthrough bleeding until end of study</time_frame>
    <description>Emicizumab FVIII-like activity (chromogenic FVIII BIOPHEN™assay system with emicizumab calibration)</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Hemophilia A</condition>
  <arm_group>
    <arm_group_label>Severe haemophila A patients with or without inhibitors</arm_group_label>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum, poor-platelet plasma, whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        100 patients with severe hemophilia A will be included in the study on 2 french Hemophilia&#xD;
        Treatement Centers (CHU Lille and CHU Caen)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult or child with Clinical diagnosis of severe hemophilia A (FVIII activity &lt; 1%)&#xD;
             with or without inhibitor&#xD;
&#xD;
          -  Clinical indication to emicizumab therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to give informed consent&#xD;
&#xD;
          -  acquired hemophilia A&#xD;
&#xD;
          -  other inherited or acquired bleeding disorder&#xD;
&#xD;
          -  bodyweight &lt; 10 kgs&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antoine Rauch, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Lille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Antoine Rauch, MD,PhD</last_name>
    <phone>0320445962</phone>
    <phone_ext>+33</phone_ext>
    <email>antoine.rauch@chru-lille.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>CHU de Caen</name>
      <address>
        <city>Caen</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Yohann Repesse, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Coeur-Poumon, Pôle d'Hématologie-Transfusion, CHU</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>0320445962</phone>
    </contact>
    <investigator>
      <last_name>Antoine Rauch, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>February 9, 2023</last_update_submitted>
  <last_update_submitted_qc>February 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Drug monitoring</keyword>
  <keyword>Severe Hemophilia A</keyword>
  <keyword>Emicizumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemophilia A</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04472169
org study id: 2019_75
secondary id: 2020-A00584-35
nct id: NCT04472169
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Emicizumab is a monoclonal bispecific antibody with a terminal half-life of 28 days which is
      now licensed in the treatment of severe haemophilia A with or without inhibitors. Some
      heterogeneity in residual emicizumab concentrations have been reported according to age, body
      mass index or drug therapeutic regimen. Some cases of neutralizing antidrug antibodies have
      been also reported. Whether monitoring emicizumab plasma concentration could predict the
      residual bleeding risk under emicizumab is unknown. As conventional coagulation assays are
      not adapted for emicizumab monitoring, this study aims to assess the value of monitoring
      residual emicizumab plasma concentration by UPLC-MS/MS in bleeding risk prediction.
observational model: Cohort
time perspective: Prospective
measure: Area under the curve ROC of Residual plasma level of emicizumab
time frame: At Week 5 (end of emicizumab loading period)
description: At least one clinically significant bleeding (defined as any bleeding treated with FVIII, rFVIIa or aPCC) from loading period completion (week 5) to the end of study, an average of 1 year
measure: Residual plasma level of emicizumab measured by UPLC-MS/MS
time frame: At Week 5 (end of emicizumab loading period)
description: At least one hemarthrosis from loading period completion (week 5) to the end of study, an average of 1 year
measure: Residual plasma level of emicizumab measured by UPLC-MS/MS
time frame: At each breakthrough bleeding until end of study
description: Post-traumatic or spontaneous nature of bleeding event
measure: Residual plasma level of emicizumab (UPLC-MS/MS dosing)
time frame: At Week 5 and at each breakthrough bleeding until end of study
description: Emicizumab FVIII-like activity (chromogenic FVIII BIOPHEN™assay system with emicizumab calibration)
arm group label: Severe haemophila A patients with or without inhibitors
Serum, poor-platelet plasma, whole blood
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Antoine Rauch, MD,PhD
role: Principal Investigator
affiliation: University Hospital, Lille
last name: Antoine Rauch, MD,PhD
phone: 0320445962
phone ext: +33
email: antoine.rauch@chru-lille.fr
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Hemophilia A