<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/NCT04410965</url>
  </required_header>
  <id_info>
    <org_study_id>BDR16019</org_study_id>
    <secondary_id>U1111-1233-0136</secondary_id>
    <nct_id>NCT04410965</nct_id>
  </id_info>
  <brief_title>Evaluation of the Relationship Between ABCG2 Mutation and Teriflunomide Exposure and Safety in Chinese RMS Patients Treated With Teriflunomide 14 mg Once Daily for 24 Weeks</brief_title>
  <acronym>TERI-PK</acronym>
  <official_title>Evaluation of the Relationship Between ABCG2 Mutation and Teriflunomide Exposure and Safety in Chinese RMS Patients Treated With Teriflunomide 14 mg Once Daily for 24 Weeks</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</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>
      Primary Objective:&#xD;
&#xD;
      Evaluate the relationship between ABCG2 mutation (rs2231142) and teriflunomide exposure,&#xD;
      during 6-month treatment with teriflunomide 14 mg&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
      Characterize the safety (AEs, such as ALT enhancement, hair thinning, diarrhea, nausea, etc.)&#xD;
      during 6-month treatment with teriflunomide&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study duration per participant is approximately 28 weeks including a 24-week treatment period&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 20, 2020</start_date>
  <completion_date type="Actual">July 12, 2021</completion_date>
  <primary_completion_date type="Actual">July 12, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PK exposure: Cmax</measure>
    <time_frame>From Week 8 to Week 24</time_frame>
    <description>PK exposure Cmax will be estimated by PopPK analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK exposure: AUCtau</measure>
    <time_frame>From Week 8 to Week 24</time_frame>
    <description>PK exposure AUCtau will be estimated by PopPK analysis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Participants with Serious Adverse Events and Adverse Events</measure>
    <time_frame>Screening to Week 24</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>teriflunomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>daily oral administration of teriflunomide 14 mg for 24 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TERIFLUNOMIDE</intervention_name>
    <description>Pharmaceutical form:tablet Route of administration: oral</description>
    <arm_group_label>teriflunomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
        Participants are eligible to be included in the study only if all the following criteria&#xD;
        apply:&#xD;
&#xD;
          -  Participant must be 18 to 55 years of age inclusive, at the time of signing the&#xD;
             informed consent.&#xD;
&#xD;
          -  Participants EDSS score ≤ 5.5 according to the diagnosis of the neurologist (using the&#xD;
             2017 Revised McDonald Diagnostic Criteria for MS) and upon treatment initiation with&#xD;
             teriflunomide according to the approved product information in China.&#xD;
&#xD;
          -  Participants will be genotyped for the rs2231142 mutation, enrolled 80 participants&#xD;
             should include: 40 wildtype patients, 40 patients with ABCG2 (rs2231142) mutation&#xD;
&#xD;
          -  Male and/or female participants:&#xD;
&#xD;
               -  Male participants: A male participant must agree to use contraception during the&#xD;
                  intervention period and undergo the accelerated eliminated procedure after the&#xD;
                  last dose of study intervention and refrain from donating sperm during this&#xD;
                  period.&#xD;
&#xD;
               -  Female participants: A female participant is eligible to participate if she is&#xD;
                  not pregnant, not breastfeeding, and not a woman of childbearing potential&#xD;
                  (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during the&#xD;
                  intervention period and undergo the accelerated elimination procedure (if&#xD;
                  necessary) after the last dose of study intervention.&#xD;
&#xD;
          -  Participants who has signed written informed consent prior to entering the screening&#xD;
             phase of the study&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
        Participants are excluded from the study if any of the following criteria apply:&#xD;
&#xD;
          -  Participant not willing /being able to complete the questionnaires and examination.&#xD;
&#xD;
          -  Participants who have taken leflunomide within 2 years prior to screening.&#xD;
&#xD;
          -  Participants who have taken teriflunomide within 2 years prior to screening.&#xD;
&#xD;
          -  Participants with severe hepatic impairment, including active hepatitis B/C diagnosed.&#xD;
&#xD;
          -  Known history of active tuberculosis (TB) or latent TB infection not adequately&#xD;
             treated, either diagnosed by standard medical practice or guidelines.&#xD;
&#xD;
          -  Relapse within 30 days prior to enrollment.&#xD;
&#xD;
          -  Participants who have any contraindications to AUBAGIO according to the local product&#xD;
             insert leaflet.&#xD;
&#xD;
          -  History of a hypersensitivity of teriflunomide, leflunomide, or any the inactive&#xD;
             ingredients in Aubagio.&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) positive patients.&#xD;
&#xD;
          -  Participants treated with:&#xD;
&#xD;
               -  glatiramer acetate, interferons, or dimethyl fumarate within 1 month prior to&#xD;
                  enrollment.&#xD;
&#xD;
               -  fingolimod, or intravenous immunoglobulins within 3 months prior to enrollment.&#xD;
&#xD;
               -  natalizumab, other immunosuppressant or immunomodulatory agents, such as&#xD;
                  cyclophosphamide, azathioprine, cyclosporine, methotrexate, mycophenolate, within&#xD;
                  24 weeks prior to enrollment.&#xD;
&#xD;
               -  cladribine or mitoxantrone within 2 years prior to enrollment.&#xD;
&#xD;
               -  adrenocorticotrophic hormone (ACTH) or systemic corticosteroids for 2 weeks prior&#xD;
                  to enrollment.&#xD;
&#xD;
          -  Participant treated with BCRP inhibitors (such as cyclosporine, eltrombopag,&#xD;
             gefitinib).&#xD;
&#xD;
          -  Participant not suitable for participation, as judged by the Investigator, including&#xD;
             medical or clinical conditions, or participants potentially at risk of noncompliance&#xD;
             to study procedures.&#xD;
&#xD;
          -  Any specific situation during study implementation/course that may rise ethics&#xD;
             considerations.&#xD;
&#xD;
          -  Sensitivity to any of the study interventions, or components thereof, or drug or other&#xD;
             allergy that, in the opinion of the Investigator, contraindicates participation in the&#xD;
             study.&#xD;
&#xD;
        The above information is not intended to contain all considerations relevant to a patient's&#xD;
        potential participation in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site Number</name>
      <address>
        <city>China</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>April 5, 2022</last_update_submitted>
  <last_update_submitted_qc>April 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2022</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>Multiple Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Teriflunomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org</ipd_description>
  </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/NCT04410965
org study id: BDR16019
secondary id: U1111-1233-0136
nct id: NCT04410965
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Primary Objective:

      Evaluate the relationship between ABCG2 mutation (rs2231142) and teriflunomide exposure,
      during 6-month treatment with teriflunomide 14 mg

      Secondary Objective:

      Characterize the safety (AEs, such as ALT enhancement, hair thinning, diarrhea, nausea, etc.)
      during 6-month treatment with teriflunomide
Study duration per participant is approximately 28 weeks including a 24-week treatment period
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PK exposure: Cmax
time frame: From Week 8 to Week 24
description: PK exposure Cmax will be estimated by PopPK analysis.
measure: PK exposure: AUCtau
time frame: From Week 8 to Week 24
description: PK exposure AUCtau will be estimated by PopPK analysis
measure: Participants with Serious Adverse Events and Adverse Events
time frame: Screening to Week 24
arm group label: teriflunomide
arm group type: Experimental
description: daily oral administration of teriflunomide 14 mg for 24 weeks
intervention type: Drug
intervention name: TERIFLUNOMIDE
description: Pharmaceutical form:tablet Route of administration: oral
arm group label: teriflunomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
country: China
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Teriflunomide
sharing ipd: Yes
ipd description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org