<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/NCT04466150</url>
  </required_header>
  <id_info>
    <org_study_id>RO-IIS-2018-10828</org_study_id>
    <nct_id>NCT04466150</nct_id>
  </id_info>
  <brief_title>Impact of Ocrelizumab on Cerebrospinal Fluid Biomarkers at Multiple Sclerosis Onset</brief_title>
  <acronym>IMPACT MS</acronym>
  <official_title>Impact of Ocrelizumab on Cerebrospinal Fluid Biomarkers at Multiple Sclerosis Onset</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Valhalla Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Newly diagnosed relapsing multiple sclerosis (MS) and high risk clinically isolated syndrome&#xD;
      (CIS) patients will be treated with ocrelizumab at disease onset to see if treatment&#xD;
      favorably alters CSF markers of chronic inflammation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Newly diagnosed relapsing multiple sclerosis (MS) and high risk clinically isolated syndrome&#xD;
      (CIS) patients age 18-50 will be treated with ocrelizumab within 90 days of first clinical&#xD;
      MS/CIS presentation and re-dosed as maintenance therapy every 6 months for 3 years to see if&#xD;
      treatment favorably alters CSF markers of chronic inflammation&#xD;
&#xD;
      Investigators hope data that will provide a foundation for further studies that treating&#xD;
      relapsing MS patients at clinical onset (using a B-cell depleting therapy) may improve&#xD;
      longer-term outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 30, 2020</start_date>
  <completion_date type="Anticipated">July 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a nested case-controlled study.&#xD;
By nesting this ocrelizumab interventional treatment arm within an observational study, the investigators will be able to compare treatment with ocrelizumab to usual care for patients who are matched for the same disease duration. Because the same clinical and biomarker assessments will be acquired for both the ocrelizumab interventional arm and the usual care observational cohort, this study will allow direct comparison of ocrelizumab with a usual care control group.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Comparison of intrathecal synthesis of gammaglobulins in treatment-naïve relapsing MS and clinically isolated syndrome participants before and after treatment with ocrelizumab</measure>
    <time_frame>3 years</time_frame>
    <description>Comparison of intrathecal synthesis of gammaglobulins in treatment-naïve relapsing MS and clinically isolated syndrome participants before and after 3 years of treatment with ocrelizumab. Intrathecal synthesis is measured by either a) normalization of the IgG Index (0.6 is the upper limit of normal) or b) eradication of oligoclonal bands</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Relapsing Multiple Sclerosis</condition>
  <condition>Clinically Isolated Syndrome</condition>
  <arm_group>
    <arm_group_label>Ocrelizumab treated</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants age 18-50 with a first clinical presentation of MS or high-risk CIS diagnosed within 90 days of screening will be treated with ocrelizumab (300 mg IV x 2 doses given 2 weeks apart) at disease origin and with maintenance ocrelizumab 600 mg every 6 months through 30 months with a final study visit at 3 years</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observational study cohort</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subjects enrolled into an observational study matched for the same disease duration and who are either untreated or treated with alternate MS disease modifying therapies will serve as a parallel reference group</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ocrelizumab</intervention_name>
    <description>open label biomarker study</description>
    <arm_group_label>Ocrelizumab treated</arm_group_label>
    <other_name>Ocrevus</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients must meet the following criteria to be included in this study:&#xD;
&#xD;
          -  Signed Consent Form&#xD;
&#xD;
          -  High-risk clinically isolated syndrome or relapsing MS Diagnosis (based on 2017&#xD;
             International Panel Criteria)&#xD;
&#xD;
          -  Age 18-50 inclusive&#xD;
&#xD;
          -  Screening within 90 days of first clinical demyelinating event typical of MS with 1 or&#xD;
             more inactive lesions typical of MS&#xD;
&#xD;
          -  No prior MS disease modifying therapy&#xD;
&#xD;
          -  No corticosteroids within 7 days of first ocrelizumab treatment&#xD;
&#xD;
          -  EDSS &lt; 4.0&#xD;
&#xD;
          -  A negative urine or serum pregnancy test must be available for premenopausal women and&#xD;
             for women &lt;12 months after the onset of menopause, unless they have undergone surgical&#xD;
             sterilization.&#xD;
&#xD;
          -  Women of childbearing potential must agree to remain abstinent (refrain from&#xD;
             heterosexual intercourse) or use one method of contraception with a failure rate of&#xD;
             &lt;1% per year or a barrier method supplemented with spermicide. Contraception must&#xD;
             continue for the duration of study treatment and for at least 24 weeks after the last&#xD;
             dose of study treatment. A woman is considered to be of childbearing potential if she&#xD;
             is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of&#xD;
             amenorrhea with no identified cause of other than menopause), and has not undergone&#xD;
             surgical sterilization (removal of the ovaries and/or uterus).&#xD;
&#xD;
               -  Examples of contraceptive methods with a failure rate of &lt;1% per year include&#xD;
                  bilateral tube ligation, male sterilization, established hormonal contraceptives&#xD;
                  that inhibit ovulation, hormone-releasing intrauterine devices, and copper&#xD;
                  intrauterine devices.&#xD;
&#xD;
               -  The reliability of sexual abstinence should be evaluated in relation to the&#xD;
                  duration of the clinical trial and the preferred and usual lifestyle of the&#xD;
                  patient. Periodic abstinence and withdrawal are not acceptable methods of&#xD;
                  contraception.&#xD;
&#xD;
               -  Examples of barrier methods supplemented with the use of spermicide include male&#xD;
                  or female condom, cap, diaphragm, or sponge.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients will be excluded from the study based on the following criteria:&#xD;
&#xD;
          -  Pregnancy, lactation, or intention to become pregnant during the study&#xD;
&#xD;
          -  Progressive MS (primary or secondary)&#xD;
&#xD;
          -  Disease other than MS to explain the first demyelinating event; including AQP4 IgG&#xD;
             seropositivity&#xD;
&#xD;
          -  Unwilling or unsafe to proceed with CSF exams based on coagulopathy or anatomy or&#xD;
             other considerations in the judgment of the study investigator&#xD;
&#xD;
          -  Unwilling or unsafe to proceed with MRI&#xD;
&#xD;
          -  Active hepatitis B virus infection&#xD;
&#xD;
          -  Untreated latent or active tuberculosis&#xD;
&#xD;
          -  Active hepatitis C virus infection&#xD;
&#xD;
          -  HIV infection&#xD;
&#xD;
          -  Hypersensitivity to trial medications&#xD;
&#xD;
          -  History of life-threatening infusion reaction to MAbs&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruce Cree, MD, PhD, MAS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Robin Lincoln, BS</last_name>
    <phone>415-502-7216</phone>
    <email>robin.lincoln@ucsf.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Naomi Okinishi, BS MPH</last_name>
    <phone>415-502-7604</phone>
    <email>naomi.okinishi@ucsf.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>June 27, 2023</last_update_submitted>
  <last_update_submitted_qc>June 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2023</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>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ocrelizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Outcome data (biomarker, genotypic) as well as study data related to diagnosis, disease presentation, and date of birth, along with biological specimens collected as part of the study, may be shared (in coded form) in the future with other qualified researchers, government data registries, and/or commercial entities on a case by case basis at the discretion of the PI and Co-PIs. Any such investigator/entity will be required to provide appropriate documentation that the research being conducted has been approved by an Institutional Review Board and demonstrate that it will be of scientific value.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Clinical study report to Sponsor estimated May 2025. Other data/samples will be shared after initial results are published and on a case by case basis.</ipd_time_frame>
    <ipd_access_criteria>Collaborators, other scientific Investigators, Government Health and research agencies, Commercial Companies may request data and/or samples. The request process includes submitting a research proposal, having necessary IRB approval and material transfer agreements.</ipd_access_criteria>
  </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/NCT04466150
org study id: RO-IIS-2018-10828
nct id: NCT04466150
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Newly diagnosed relapsing multiple sclerosis (MS) and high risk clinically isolated syndrome
      (CIS) patients will be treated with ocrelizumab at disease onset to see if treatment
      favorably alters CSF markers of chronic inflammation.
Newly diagnosed relapsing multiple sclerosis (MS) and high risk clinically isolated syndrome
      (CIS) patients age 18-50 will be treated with ocrelizumab within 90 days of first clinical
      MS/CIS presentation and re-dosed as maintenance therapy every 6 months for 3 years to see if
      treatment favorably alters CSF markers of chronic inflammation

      Investigators hope data that will provide a foundation for further studies that treating
      relapsing MS patients at clinical onset (using a B-cell depleting therapy) may improve
      longer-term outcomes.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: This is a nested case-controlled study.
By nesting this ocrelizumab interventional treatment arm within an observational study, the investigators will be able to compare treatment with ocrelizumab to usual care for patients who are matched for the same disease duration. Because the same clinical and biomarker assessments will be acquired for both the ocrelizumab interventional arm and the usual care observational cohort, this study will allow direct comparison of ocrelizumab with a usual care control group.
primary purpose: Basic Science
masking: None (Open Label)
measure: Comparison of intrathecal synthesis of gammaglobulins in treatment-naïve relapsing MS and clinically isolated syndrome participants before and after treatment with ocrelizumab
time frame: 3 years
description: Comparison of intrathecal synthesis of gammaglobulins in treatment-naïve relapsing MS and clinically isolated syndrome participants before and after 3 years of treatment with ocrelizumab. Intrathecal synthesis is measured by either a) normalization of the IgG Index (0.6 is the upper limit of normal) or b) eradication of oligoclonal bands
arm group label: Ocrelizumab treated
arm group type: Active Comparator
description: Participants age 18-50 with a first clinical presentation of MS or high-risk CIS diagnosed within 90 days of screening will be treated with ocrelizumab (300 mg IV x 2 doses given 2 weeks apart) at disease origin and with maintenance ocrelizumab 600 mg every 6 months through 30 months with a final study visit at 3 years
arm group label: Observational study cohort
arm group type: No Intervention
description: Subjects enrolled into an observational study matched for the same disease duration and who are either untreated or treated with alternate MS disease modifying therapies will serve as a parallel reference group
intervention type: Drug
intervention name: Ocrelizumab
description: open label biomarker study
arm group label: Ocrelizumab treated
other name: Ocrevus
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Bruce Cree, MD, PhD, MAS
role: Principal Investigator
affiliation: University of California, San Francisco
last name: Robin Lincoln, BS
phone: 415-502-7216
email: robin.lincoln@ucsf.edu
last name: Naomi Okinishi, BS MPH
phone: 415-502-7604
email: naomi.okinishi@ucsf.edu
facility: 
status: Recruiting
country: United States
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citation: Rejdak K, Stelmasiak Z, Grieb P. Cladribine induces long lasting oligoclonal bands disappearance in relapsing multiple sclerosis patients: 10-year observational study. Mult Scler Relat Disord. 2019 Jan;27:117-120. doi: 10.1016/j.msard.2018.10.006. Epub 2018 Oct 10.
PMID: 30368223
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citation: https://www.emdserono.com/content/dam/web/corporate/non-images/country-specifics/us/pi/mavenclad-pi.pdf
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responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis
mesh term: Ocrelizumab
sharing ipd: Yes
ipd description: Outcome data (biomarker, genotypic) as well as study data related to diagnosis, disease presentation, and date of birth, along with biological specimens collected as part of the study, may be shared (in coded form) in the future with other qualified researchers, government data registries, and/or commercial entities on a case by case basis at the discretion of the PI and Co-PIs. Any such investigator/entity will be required to provide appropriate documentation that the research being conducted has been approved by an Institutional Review Board and demonstrate that it will be of scientific value.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Clinical study report to Sponsor estimated May 2025. Other data/samples will be shared after initial results are published and on a case by case basis.
ipd access criteria: Collaborators, other scientific Investigators, Government Health and research agencies, Commercial Companies may request data and/or samples. The request process includes submitting a research proposal, having necessary IRB approval and material transfer agreements.