<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/NCT04480307</url>
  </required_header>
  <id_info>
    <org_study_id>GNC-401</org_study_id>
    <secondary_id>2019-004822-15</secondary_id>
    <nct_id>NCT04480307</nct_id>
  </id_info>
  <brief_title>Clinical Trial Assessing Temelimab Following Rituximab Treatment in Patients With Relapsing Forms of Multiple Sclerosis</brief_title>
  <acronym>ProTEct-MS</acronym>
  <official_title>A Randomized, Double-Blind, Placebo Controlled Trial, Examining the Safety, Tolerability, Pharmacodynamic Effects and Pharmacokinetics of Temelimab Following Rituximab Treatment in Patients With Relapsing Forms of Multiple Sclerosis (RMS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GeNeuro Innovation SAS</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GeNeuro SA</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>
      Randomized, double-blind, placebo-controlled Phase IIa clinical study, assessing safety,&#xD;
      tolerability, pharmacodynamic effects and pharmacokinetics of temelimab, administered at&#xD;
      three different dose levels (18 mg/kg or 36 mg/kg or 54 mg/kg).&#xD;
&#xD;
      In this study temelimab is administered subsequently to rituximab therapy, i.e. no&#xD;
      co-administration of rituximab and temelimab is done in this study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 17, 2020</start_date>
  <completion_date type="Actual">January 24, 2022</completion_date>
  <primary_completion_date type="Actual">January 24, 2022</primary_completion_date>
  <phase>Phase 2</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>Safety and tolerability: adverse event</measure>
    <time_frame>48 weeks</time_frame>
    <description>To determine if temelimab treatment is associated with an increase of adverse event</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neuroimaging</measure>
    <time_frame>48 weeks</time_frame>
    <description>Change in brain parenchymal volume fraction at Week 48 compared to Baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuroimaging</measure>
    <time_frame>48 weeks</time_frame>
    <description>Change in magnetization transfer (MTR) in periventricular NAWM at Week 48 compared to Baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuroimaging</measure>
    <time_frame>48 weeks</time_frame>
    <description>Change in thalamic volume fraction at Week 48 compared to Baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuroimaging</measure>
    <time_frame>48 weeks</time_frame>
    <description>Change in magnetization transfer (MTR) in cortex at Week 48 compared to Baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuroimaging</measure>
    <time_frame>48 weeks</time_frame>
    <description>Change in T1 and T2 lesion volume at Week 48 compared to Baseline</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>temelimab 18 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Monthly IV repeated dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>temelimab 36 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Monthly IV repeated dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>temelimab 54 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Monthly IV repeated dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Monthly IV repeated dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>temelimab 18 mg/kg</intervention_name>
    <description>temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).</description>
    <arm_group_label>temelimab 18 mg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>temelimab 36 mg/kg</intervention_name>
    <description>temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).</description>
    <arm_group_label>temelimab 36 mg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>temelimab 54 mg/kg</intervention_name>
    <description>temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).</description>
    <arm_group_label>temelimab 54 mg/kg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          -  Current diagnosis of RMS, based on McDonald 2017 criteria&#xD;
&#xD;
          -  Having received treatment with rituximab, as per local clinical routine for at least&#xD;
             12 months prior to the Screening Visit&#xD;
&#xD;
          -  Having received their last dose of rituximab not more than 8 weeks and not less than 4&#xD;
             weeks before Randomization (Study Day 1)&#xD;
&#xD;
          -  Having expanded disability status scale (EDSS) 2.5 - 5.5 inclusive at Screening&#xD;
&#xD;
          -  Present clinical worsening in one or more neurological domains as assessed by EDSS,&#xD;
             ambulatory function as assessed by 6MWT or T25FW, cognitive functioning as assessed by&#xD;
             SDMT or increased need of walking aids or pharmacological/procedures for bowel and&#xD;
             bladder functions over the last year.&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          -  Current diagnosis of primary progressive MS (PPMS)&#xD;
&#xD;
          -  Any disease other than MS (e.g. myelitis and /or bilateral optic neuritis) that could&#xD;
             better explain the patient's signs and symptoms&#xD;
&#xD;
          -  Usage of any of the following medications prior to the Screening visit:&#xD;
&#xD;
               -  Any usage of interferon beta, glatiramer acetate, IV immunoglobulin (IVIG),&#xD;
                  dimethyl fumarate or teriflunomide within 12 months prior to Screening,&#xD;
&#xD;
               -  Any history of exposure to mitoxantrone, cladribine, alemtuzumab,&#xD;
                  cyclophosphamide, systemic cytotoxic therapy, total lymphoid irradiation, and/or&#xD;
                  bone marrow transplantation at any time,&#xD;
&#xD;
               -  Any usage of natalizumab within 24 months prior to Screening,&#xD;
&#xD;
               -  Any usage of highly potent immune modulating therapy, such as: ocrelizumab,&#xD;
                  ofatumumab, fingolimod, siponimod, ozanimod or anti-cytokine therapy,&#xD;
                  plasmapheresis or azathioprine within 12 months prior to Screening,&#xD;
&#xD;
               -  Any usage of any experimental treatment if not washed out for ≥ 5 half-lives or ≥&#xD;
                  12 months (whichever is longer), except rituximab which is allowed before the&#xD;
                  study.&#xD;
&#xD;
          -  CTCAE Grade 2 or greater lymphopenia&#xD;
&#xD;
          -  Any major medical or psychiatric disorder that would affect the capacity of the&#xD;
             patient to fulfill the requirements of the study&#xD;
&#xD;
          -  History or presence of serious or acute heart disease such as uncontrolled cardiac&#xD;
             dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or&#xD;
             uncontrolled congestive heart failure (NYHA class 3 or 4)&#xD;
&#xD;
          -  Any history of cancer with the exceptions of basal cell carcinoma and/or carcinoma in&#xD;
             situ of the cervix, and only if successfully treated by complete surgical resection,&#xD;
             with documented clean margins and any medically unstable condition as determined by&#xD;
             the investigator&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#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>David Leppert, MD</last_name>
    <role>Study Director</role>
    <affiliation>GeNeuro Innovation SAS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Neurology, Academic Specialist Center</name>
      <address>
        <city>Stockholm</city>
        <zip>113 65</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>July 4, 2022</last_update_submitted>
  <last_update_submitted_qc>July 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Relapsing Forms of Multiple Sclerosis</keyword>
  <keyword>GNbAC1</keyword>
  <keyword>Human Endogenous Retrovirus Type W</keyword>
  <keyword>HERV-W</keyword>
  <keyword>Temelimab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</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/NCT04480307
org study id: GNC-401
secondary id: 2019-004822-15
nct id: NCT04480307
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Randomized, double-blind, placebo-controlled Phase IIa clinical study, assessing safety,
      tolerability, pharmacodynamic effects and pharmacokinetics of temelimab, administered at
      three different dose levels (18 mg/kg or 36 mg/kg or 54 mg/kg).

      In this study temelimab is administered subsequently to rituximab therapy, i.e. no
      co-administration of rituximab and temelimab is done in this study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety and tolerability: adverse event
time frame: 48 weeks
description: To determine if temelimab treatment is associated with an increase of adverse event
measure: Neuroimaging
time frame: 48 weeks
description: Change in brain parenchymal volume fraction at Week 48 compared to Baseline
measure: Neuroimaging
time frame: 48 weeks
description: Change in magnetization transfer (MTR) in periventricular NAWM at Week 48 compared to Baseline
measure: Neuroimaging
time frame: 48 weeks
description: Change in thalamic volume fraction at Week 48 compared to Baseline
measure: Neuroimaging
time frame: 48 weeks
description: Change in magnetization transfer (MTR) in cortex at Week 48 compared to Baseline
measure: Neuroimaging
time frame: 48 weeks
description: Change in T1 and T2 lesion volume at Week 48 compared to Baseline
arm group label: temelimab 18 mg/kg
arm group type: Experimental
description: Monthly IV repeated dose
arm group label: temelimab 36 mg/kg
arm group type: Experimental
description: Monthly IV repeated dose
arm group label: temelimab 54 mg/kg
arm group type: Experimental
description: Monthly IV repeated dose
arm group label: Placebo
arm group type: Placebo Comparator
description: Monthly IV repeated dose
intervention type: Drug
intervention name: temelimab 18 mg/kg
description: temelimab 18 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
arm group label: temelimab 18 mg/kg
intervention type: Drug
intervention name: temelimab 36 mg/kg
description: temelimab 36 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
arm group label: temelimab 36 mg/kg
intervention type: Drug
intervention name: temelimab 54 mg/kg
description: temelimab 54 mg/kg will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
arm group label: temelimab 54 mg/kg
intervention type: Drug
intervention name: Placebo
description: Placebo will be given as monthly (4-weekly) intravenous (IV) infusions over 48 weeks (12 administrations in total).
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: David Leppert, MD
role: Study Director
affiliation: GeNeuro Innovation SAS
facility: 
country: Sweden
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis