<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/NCT04478591</url>
  </required_header>
  <id_info>
    <org_study_id>2020.191</org_study_id>
    <nct_id>NCT04478591</nct_id>
  </id_info>
  <brief_title>The Wearing-off Phenomenon of Ocrelizumab in Patients With Multiple Sclerosis</brief_title>
  <acronym>WOC</acronym>
  <official_title>The Wearing-off Phenomenon of Ocrelizumab in Patients With Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amsterdam UMC, location VUmc</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amsterdam UMC, location VUmc</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>
      The primary goal of this research is to study the prevalence of the wearing-off effect and&#xD;
      possible risk factors for wearing-off symptoms in patients with multiple sclerosis using&#xD;
      ocrelizumab with the use of questionnaires. Furthermore, the goal is to study whether&#xD;
      patients receiving extended dosing of ocrelizumab experience more wearing-off symptoms or&#xD;
      adverse events in general. Finally, we would like to extend knowledge on wearing-off symptoms&#xD;
      in general.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ocrelizumab is a monoclonal antibody very effective for the treatment of relapsing-remitting&#xD;
      multiple sclerosis and primary progressive multiple sclerosis. Ocrelizumab is usually&#xD;
      administered intravenous every six months. Natalizumab is another type of treatment used for&#xD;
      relapsing-remitting multiple sclerosis and is administered every four weeks. Often patients&#xD;
      report MS-related symptoms just prior to their next infusion such as fatigue, coordination&#xD;
      problems or motor problems, the so-called wearing-off phenomenon. The exact etiology of this&#xD;
      phenomenon remains unknown. Although not studied before, patients do report similar symptoms&#xD;
      when using ocrelizumab. Furthermore, because of the COVID-19 pandemic, some patients receive&#xD;
      extended dosing of ocrelizumab based on b-cell count. Whether this can increase wearing-off&#xD;
      symptoms is unknown.&#xD;
&#xD;
      The goal of this research is to study the prevalence of wearing-off symptoms and possible&#xD;
      risk factors for wearing-off symptoms in patients with multiple sclerosis using ocrelizumab.&#xD;
      All patients using ocrelizumab during one year or more that provided written informed consent&#xD;
      to participate in the study will be asked to complete three questionnaires before or during&#xD;
      their next treatment with ocrelizumab. The questionnaires that will be used are the MSIS-29,&#xD;
      the treatment satisfaction questionnaire and a questionnaire about wearing-off symptoms.&#xD;
      Exact weight of the participants will be measured. Information about age, gender, date of&#xD;
      diagnosis, start date of ocrelizumab, clinical and radiological disease activity, EDSS score,&#xD;
      b-cell count and the biomarker neurofilament light will be extracted from the patient files.&#xD;
      After two weeks, participants receive two additional digital questionnaires, the MSIS-29 and&#xD;
      a follow-up questionnaire about wearing-off symptoms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 12, 2020</start_date>
  <completion_date type="Actual">May 1, 2021</completion_date>
  <primary_completion_date type="Actual">April 1, 2021</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>Wearing-off symptoms</measure>
    <time_frame>Baseline</time_frame>
    <description>Prevalence of wearing-off symptoms prior to ocrelizumab infusion (yes/no assessed on questionnaires)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>% of wearing-off symptoms (yes/no assessed on questionnaires) in correlation to the % of patients with extended dosing versus standard dosing with ocrelizumab.</measure>
    <time_frame>At baseline (prior to next infusion with ocrelizumab)</time_frame>
    <description>% of wearing-off symptoms (yes/no assessed on questionnaires) in correlation to the % of patients with extended dosing versus standard dosing with ocrelizumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurofilament light levels in patients with wearing-off symptoms.</measure>
    <time_frame>At baseline (prior to next infusion with ocrelizumab)</time_frame>
    <description>Neurofilament light levels in patients with wearing-off symptoms compared to patients without wearing-off symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute B-cells count in blood in correlation to the presence of wearing-off symptoms (yes/no assessed on questionnaires)</measure>
    <time_frame>At baseline (prior to next infusion with ocrelizumab)</time_frame>
    <description>Absolute B-cells count in blood in correlation to the presence of wearing-off symptoms (yes/no assessed on questionnaires) levels in patients with wearing-off symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type of multiple sclerosis (either RRMS or PPMS) in correlation to % of patients with wearing-off symptoms (yes/no assessed on questionnaires).</measure>
    <time_frame>At baseline (prior to next infusion with ocrelizumab)</time_frame>
    <description>Type of multiple sclerosis (either RRMS or PPMS) in correlation to % of patients with wearing-off symptoms (yes/no assessed on questionnaires).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment satisfaction score measured by the treatment satisfaction questionnaire in correlation to the % of patients with wearing-off symptoms (yes/no assessed on questionnaires)</measure>
    <time_frame>At baseline (prior to next infusion with ocrelizumab)</time_frame>
    <description>Treatment satisfaction score measured by the treatment satisfaction questionnaire in correlation to the % of patients with wearing-off symptoms (yes/no assessed on questionnaires)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported disability (MSIS-29 questionnaire) compared before and after ocrelizumab infusion in patients with wearing-off symptoms</measure>
    <time_frame>At baseline (prior to next infusion with ocrelizumab) and after two weeks</time_frame>
    <description>Self-reported disability before ocrelizumab infusion compared before and after ocrelizumab (delta scores) in patients with wearing-off symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Self-reported disability (MSIS-29 questionnaire) after ocrelizumab infusion in patients without wearing-off symptoms</measure>
    <time_frame>At baseline (prior to next infusion with ocrelizumab) and after two weeks</time_frame>
    <description>Self-reported disability after ocrelizumab infusioSelf-reported disability before ocrelizumab infusion compared before and after ocrelizumab (delta scores) in patients with wearing-off symptomsn in patients without wearing-off symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of wearing-off symptoms after ocrelizumab infusion in patients with wearing-off symptoms</measure>
    <time_frame>Two weeks after ocrelizumab infusion</time_frame>
    <description>Change of wearing-off symptoms after ocrelizumab infusion in patients with wearing-off symptoms as measured with the wearing-off questionnaire (questionnaire designed for this study evaluating wearing-off symptoms).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-dose symptoms after ocrelizumab infusion</measure>
    <time_frame>Two weeks after ocrelizumab infusion</time_frame>
    <description>Post-dose symptoms after ocrelizumab infusion as measured with the wearing-off questionnaire (questionnaire designed for this study evaluating wearing-off symptoms).</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">117</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Patients with multiple sclerosis using ocrelizumab.</arm_group_label>
    <description>Patients with multiple sclerosis using ocrelizumab for a minimum of one year.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaires</intervention_name>
    <description>All participants will fill in two questionnaires before or during their next treatment with ocrelizumab: the MSIS-29 questionnaire and a wearing-off questionnaire. After two weeks, participants fill in two digital questionnaires (MSIS-29, additional wearing-off questionnaire).</description>
    <arm_group_label>Patients with multiple sclerosis using ocrelizumab.</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with multiple sclerosis using ocrelizumab.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years or older&#xD;
&#xD;
          -  Diagnosis multiple sclerosis&#xD;
&#xD;
          -  Use of ocrelizumab as a treatment for multiple sclerosis for a minimum of one year&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to answer questionnaires in Dutch&#xD;
&#xD;
          -  Different infusion protocol during the previous ocrelizumab infusion (e.g. 300 mg of&#xD;
             ocrelizumab instead of 600 mg).&#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>Joep Killestein, MD, PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Amsterdam UMC, location VUmc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Amsterdam UMC, location VUmc</name>
      <address>
        <city>Amsterdam</city>
        <state>North-Holland</state>
        <zip>1007 MB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>September 22, 2021</last_update_submitted>
  <last_update_submitted_qc>September 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Amsterdam UMC, location VUmc</investigator_affiliation>
    <investigator_full_name>Zoé van Kempen</investigator_full_name>
    <investigator_title>principal investigator</investigator_title>
  </responsible_party>
  <keyword>Multiple Sclerosis</keyword>
  <keyword>Ocrelizumab</keyword>
  <keyword>Wearing-off effect</keyword>
  <keyword>Neurofilament Light</keyword>
  <keyword>Extended dosing</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>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04478591
org study id: 2020.191
nct id: NCT04478591
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary goal of this research is to study the prevalence of the wearing-off effect and
      possible risk factors for wearing-off symptoms in patients with multiple sclerosis using
      ocrelizumab with the use of questionnaires. Furthermore, the goal is to study whether
      patients receiving extended dosing of ocrelizumab experience more wearing-off symptoms or
      adverse events in general. Finally, we would like to extend knowledge on wearing-off symptoms
      in general.
Ocrelizumab is a monoclonal antibody very effective for the treatment of relapsing-remitting
      multiple sclerosis and primary progressive multiple sclerosis. Ocrelizumab is usually
      administered intravenous every six months. Natalizumab is another type of treatment used for
      relapsing-remitting multiple sclerosis and is administered every four weeks. Often patients
      report MS-related symptoms just prior to their next infusion such as fatigue, coordination
      problems or motor problems, the so-called wearing-off phenomenon. The exact etiology of this
      phenomenon remains unknown. Although not studied before, patients do report similar symptoms
      when using ocrelizumab. Furthermore, because of the COVID-19 pandemic, some patients receive
      extended dosing of ocrelizumab based on b-cell count. Whether this can increase wearing-off
      symptoms is unknown.

      The goal of this research is to study the prevalence of wearing-off symptoms and possible
      risk factors for wearing-off symptoms in patients with multiple sclerosis using ocrelizumab.
      All patients using ocrelizumab during one year or more that provided written informed consent
      to participate in the study will be asked to complete three questionnaires before or during
      their next treatment with ocrelizumab. The questionnaires that will be used are the MSIS-29,
      the treatment satisfaction questionnaire and a questionnaire about wearing-off symptoms.
      Exact weight of the participants will be measured. Information about age, gender, date of
      diagnosis, start date of ocrelizumab, clinical and radiological disease activity, EDSS score,
      b-cell count and the biomarker neurofilament light will be extracted from the patient files.
      After two weeks, participants receive two additional digital questionnaires, the MSIS-29 and
      a follow-up questionnaire about wearing-off symptoms.
observational model: Cohort
time perspective: Prospective
measure: Wearing-off symptoms
time frame: Baseline
description: Prevalence of wearing-off symptoms prior to ocrelizumab infusion (yes/no assessed on questionnaires)
measure: % of wearing-off symptoms (yes/no assessed on questionnaires) in correlation to the % of patients with extended dosing versus standard dosing with ocrelizumab.
time frame: At baseline (prior to next infusion with ocrelizumab)
description: % of wearing-off symptoms (yes/no assessed on questionnaires) in correlation to the % of patients with extended dosing versus standard dosing with ocrelizumab.
measure: Neurofilament light levels in patients with wearing-off symptoms.
time frame: At baseline (prior to next infusion with ocrelizumab)
description: Neurofilament light levels in patients with wearing-off symptoms compared to patients without wearing-off symptoms.
measure: Absolute B-cells count in blood in correlation to the presence of wearing-off symptoms (yes/no assessed on questionnaires)
time frame: At baseline (prior to next infusion with ocrelizumab)
description: Absolute B-cells count in blood in correlation to the presence of wearing-off symptoms (yes/no assessed on questionnaires) levels in patients with wearing-off symptoms.
measure: Type of multiple sclerosis (either RRMS or PPMS) in correlation to % of patients with wearing-off symptoms (yes/no assessed on questionnaires).
time frame: At baseline (prior to next infusion with ocrelizumab)
description: Type of multiple sclerosis (either RRMS or PPMS) in correlation to % of patients with wearing-off symptoms (yes/no assessed on questionnaires).
measure: Treatment satisfaction score measured by the treatment satisfaction questionnaire in correlation to the % of patients with wearing-off symptoms (yes/no assessed on questionnaires)
time frame: At baseline (prior to next infusion with ocrelizumab)
description: Treatment satisfaction score measured by the treatment satisfaction questionnaire in correlation to the % of patients with wearing-off symptoms (yes/no assessed on questionnaires)
measure: Self-reported disability (MSIS-29 questionnaire) compared before and after ocrelizumab infusion in patients with wearing-off symptoms
time frame: At baseline (prior to next infusion with ocrelizumab) and after two weeks
description: Self-reported disability before ocrelizumab infusion compared before and after ocrelizumab (delta scores) in patients with wearing-off symptoms
measure: Self-reported disability (MSIS-29 questionnaire) after ocrelizumab infusion in patients without wearing-off symptoms
time frame: At baseline (prior to next infusion with ocrelizumab) and after two weeks
description: Self-reported disability after ocrelizumab infusioSelf-reported disability before ocrelizumab infusion compared before and after ocrelizumab (delta scores) in patients with wearing-off symptomsn in patients without wearing-off symptoms
measure: Change of wearing-off symptoms after ocrelizumab infusion in patients with wearing-off symptoms
time frame: Two weeks after ocrelizumab infusion
description: Change of wearing-off symptoms after ocrelizumab infusion in patients with wearing-off symptoms as measured with the wearing-off questionnaire (questionnaire designed for this study evaluating wearing-off symptoms).
measure: Post-dose symptoms after ocrelizumab infusion
time frame: Two weeks after ocrelizumab infusion
description: Post-dose symptoms after ocrelizumab infusion as measured with the wearing-off questionnaire (questionnaire designed for this study evaluating wearing-off symptoms).
arm group label: Patients with multiple sclerosis using ocrelizumab.
description: Patients with multiple sclerosis using ocrelizumab for a minimum of one year.
intervention type: Other
intervention name: Questionnaires
description: All participants will fill in two questionnaires before or during their next treatment with ocrelizumab: the MSIS-29 questionnaire and a wearing-off questionnaire. After two weeks, participants fill in two digital questionnaires (MSIS-29, additional wearing-off questionnaire).
arm group label: Patients with multiple sclerosis using ocrelizumab.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joep Killestein, MD, PhD.
role: Principal Investigator
affiliation: Amsterdam UMC, location VUmc
facility: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Amsterdam UMC, location VUmc
investigator full name: Zoé van Kempen
investigator title: principal investigator
mesh term: Multiple Sclerosis
mesh term: Sclerosis
sharing ipd: Undecided