<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/NCT02977533</url>
  </required_header>
  <id_info>
    <org_study_id>TDU14981</org_study_id>
    <secondary_id>2016-002415-18</secondary_id>
    <secondary_id>U1111-1184-8607</secondary_id>
    <nct_id>NCT02977533</nct_id>
  </id_info>
  <brief_title>A Single Ascending Dose Study of GZ402668 in Patients With Progressive Multiple Sclerosis</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Subcutaneous Dose of GZ402668 in Men and Women With Progressive Multiple Sclerosis</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To assess the safety and tolerability of GZ402668 after a single subcutaneous (SC) dose in&#xD;
      men and women with progressive multiple sclerosis.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
      To assess in men and women with progressive multiple sclerosis:&#xD;
&#xD;
        -  The pharmacokinetic (PK) parameters of GZ402668 after a single SC dose.&#xD;
&#xD;
        -  The pharmacodynamic (PD) response to GZ402668 after a single SC dose.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The total study duration from screening for a patient can be approximately up to 8 weeks.&#xD;
      Upon completion of this trial, patients treated with GZ402668 will be required to enroll in a&#xD;
      4 year safety follow-up study for continued safety observation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2016</start_date>
  <completion_date type="Actual">May 16, 2018</completion_date>
  <primary_completion_date type="Actual">May 16, 2018</primary_completion_date>
  <phase>Phase 1</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>Number of participants with treatment emergent adverse events</measure>
    <time_frame>4 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of PK parameter: maximum concentration (Cmax)</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of PK parameter: area under curve (AUC)</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with lymphocyte depletion</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with anti-drug antibodies</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with injection site reactions</measure>
    <time_frame>4 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Progressive Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>GZ402668</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose 1 (up to a maximum optional Dose 2) will be given as a single subcutaneous administration under fed conditions. Acyclovir will be given twice daily starting on Day 1 and continuing for 28 days after investigational medicinal product administration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A dose of matching placebo will be given as a single subcutaneous administration under fed conditions. Acyclovir will be given twice daily starting on Day 1 and continuing for 28 days after investigational medicinal product administration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GZ402668</intervention_name>
    <description>Pharmaceutical form: solution&#xD;
Route of administration: subcutaneous</description>
    <arm_group_label>GZ402668</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Pharmaceutical form: solution&#xD;
Route of administration: subcutaneous</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acyclovir</intervention_name>
    <description>Pharmaceutical form: tablet&#xD;
Route of administration: oral</description>
    <arm_group_label>GZ402668</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          -  Male or female adult with a diagnosis of progressive multiple sclerosis (MS) including&#xD;
             primary progressive MS, secondary progressive MS, or progressive relapsing MS.&#xD;
&#xD;
          -  Aged between 18 and 65 years, inclusive.&#xD;
&#xD;
          -  Body weight greater than 40.0 kg.&#xD;
&#xD;
          -  Female patients of child bearing potential must use 2 highly effective contraception&#xD;
             methods.&#xD;
&#xD;
          -  Male patients, whose partners are of childbearing potential (including lactating&#xD;
             women), must accept to use, during sexual intercourse, 2 highly effective&#xD;
             contraception methods. Males patient, whose partners are pregnant, must use, during&#xD;
             sexual intercourse, a condom from the inclusion up to 4 months after investigational&#xD;
             medicinal product administration.&#xD;
&#xD;
          -  Males patient who has agreed not to donate sperm for 4 months after product&#xD;
             administration.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Significant medical diseases or conditions, including poorly controlled hypertension,&#xD;
             cardiovascular disease, inflammatory disorders, immunodeficiency, autoimmune disease,&#xD;
             renal failure, liver dysfunction, cancer (except treated basal skin cell carcinoma),&#xD;
             or active infection.&#xD;
&#xD;
          -  Frequent headaches and/or migraine, recurrent nausea and/or vomiting.&#xD;
&#xD;
          -  History or presence of drug or alcohol abuse.&#xD;
&#xD;
          -  Smoking more than 5 cigarettes or equivalent per day.&#xD;
&#xD;
          -  If female, pregnancy, lactating, or breast-feeding.&#xD;
&#xD;
          -  Patients with relapsing-remitting MS.&#xD;
&#xD;
          -  Treatment with natalizumab, methotrexate, azathioprine, or cyclosporine in the past 6&#xD;
             months.&#xD;
&#xD;
          -  Treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab or any other&#xD;
             immunosuppressant or cytotoxic therapy (other than steroids) in the last 12 months, or&#xD;
             determined by the treating physician to have residual immune suppression from these&#xD;
             treatments.&#xD;
&#xD;
          -  Treatment with glatiramer acetate or interferon beta in the past 4 weeks.&#xD;
&#xD;
          -  Treatment with fingolimod within the past 2 months.&#xD;
&#xD;
          -  Treatment with dimethyl fumarate in past 4 weeks.&#xD;
&#xD;
          -  Treatment with teriflunomide within the past 12 months unless patient has completed an&#xD;
             accelerated clearance with cholestyramine.&#xD;
&#xD;
          -  Previous treatment with alemtuzumab.&#xD;
&#xD;
          -  Live, attenuated vaccine within 3 months prior to the randomization visit, such as&#xD;
             varicella-zoster, oral polio, and rubella vaccines.&#xD;
&#xD;
          -  Clinically significant abnormality in thyroid function.&#xD;
&#xD;
          -  Inability to undergo magnetic resonance imaging with gadolinium administration.&#xD;
&#xD;
          -  Hypersensitivity or contraindication to acyclovir.&#xD;
&#xD;
          -  Known bleeding disorder.&#xD;
&#xD;
          -  Significant autoimmune disease.&#xD;
&#xD;
          -  Active infection or at high risk for infection.&#xD;
&#xD;
          -  Latent or active tuberculosis.&#xD;
&#xD;
          -  Major psychiatric disorder that is not adequately controlled by treatment.&#xD;
&#xD;
          -  Epileptic seizures that are not adequately controlled by treatment.&#xD;
&#xD;
          -  Prior history of invasive fungal infections.&#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>65 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 276001</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>April 22, 2022</last_update_submitted>
  <last_update_submitted_qc>April 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 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>
    <mesh_term>Multiple Sclerosis, Chronic Progressive</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acyclovir</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/NCT02977533
org study id: TDU14981
secondary id: 2016-002415-18
secondary id: U1111-1184-8607
nct id: NCT02977533
lead sponsor: 
has dmc: No
Primary Objective:

      To assess the safety and tolerability of GZ402668 after a single subcutaneous (SC) dose in
      men and women with progressive multiple sclerosis.

      Secondary Objectives:

      To assess in men and women with progressive multiple sclerosis:

        -  The pharmacokinetic (PK) parameters of GZ402668 after a single SC dose.

        -  The pharmacodynamic (PD) response to GZ402668 after a single SC dose.
The total study duration from screening for a patient can be approximately up to 8 weeks.
      Upon completion of this trial, patients treated with GZ402668 will be required to enroll in a
      4 year safety follow-up study for continued safety observation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of participants with treatment emergent adverse events
time frame: 4 weeks
measure: Assessment of PK parameter: maximum concentration (Cmax)
time frame: 4 weeks
measure: Assessment of PK parameter: area under curve (AUC)
time frame: 4 weeks
measure: Number of participants with lymphocyte depletion
time frame: 4 weeks
measure: Number of participants with anti-drug antibodies
time frame: 4 weeks
measure: Number of participants with injection site reactions
time frame: 4 weeks
arm group label: GZ402668
arm group type: Experimental
description: Dose 1 (up to a maximum optional Dose 2) will be given as a single subcutaneous administration under fed conditions. Acyclovir will be given twice daily starting on Day 1 and continuing for 28 days after investigational medicinal product administration.
arm group label: Placebo
arm group type: Placebo Comparator
description: A dose of matching placebo will be given as a single subcutaneous administration under fed conditions. Acyclovir will be given twice daily starting on Day 1 and continuing for 28 days after investigational medicinal product administration.
intervention type: Drug
intervention name: GZ402668
description: Pharmaceutical form: solution
Route of administration: subcutaneous
arm group label: GZ402668
intervention type: Drug
intervention name: Placebo
description: Pharmaceutical form: solution
Route of administration: subcutaneous
arm group label: Placebo
intervention type: Drug
intervention name: Acyclovir
description: Pharmaceutical form: tablet
Route of administration: oral
arm group label: GZ402668
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Chronic Progressive
mesh term: Sclerosis
mesh term: Acyclovir
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