xml: <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/NCT05999604</url>
    </required_header>
    <id_info>
      <org_study_id>CBR_2022_13</org_study_id>
      <nct_id>NCT05999604</nct_id>
    </id_info>
    <brief_title>Impact of Annual Versus Biannual Infusions of Ocrelizumab in Patients With Active MS,After 2 Years of Initial Treatment, on Freedom From Radiological Disease Activity at Two Years: a Multicenter Randomized Controlled Non-inferiority Trial</brief_title>
    <acronym>WINDOCRE</acronym>
    <official_title>Impact of Annual Versus Biannual Infusions of Ocrelizumab in Patients With Active MS,After 2 Years of Initial Treatment, on Freedom From Radiological Disease Activity at Two Years: a Multicenter Randomized Controlled Non-inferiority Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fondation Ophtalmologique Adolphe de Rothschild</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fondation Ophtalmologique Adolphe de Rothschild</source>
    <oversight_info>
      <is_fda_regulated_drug>No</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>
        Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and the&#xD;
        leading cause of severe non-traumatic disability in young people, affecting 110,000 people in&#xD;
        France. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has shown remarkable efficacy&#xD;
        in Phase III trials on the inflammatory component of the disease, reducing the annualized&#xD;
        relapse rate by 46% and the rate of new T2 lesions by 80% compared with interferon-β 1a.&#xD;
  &#xD;
        The use of anti-CD20 agents, including ocrelizumab, is associated with an infectious risk&#xD;
        that increases with duration of exposure, part of which is due to the development of&#xD;
        hypo-gammaglobulinemia in relation to cumulative dose.&#xD;
  &#xD;
        Several reports suggest a persistent effect of anti-CD20 drugs in MS, with no resumption of&#xD;
        inflammatory activity after discontinuation:&#xD;
  &#xD;
          -  During the development of ocrelizumab, at the end of phase 2, after having received 3 or&#xD;
             4 semi-annual cycles of ocrelizumab, a safety period with a therapeutic window of 18&#xD;
             months was planned, before re-administration in the extension study. During this&#xD;
             therapeutic window, the annualized relapse rate remained stable, and patients showed no&#xD;
             radiological disease activity.&#xD;
  &#xD;
          -  Scandinavian observational studies of &quot;off-label&quot; use of anti-CD20 in MS provide&#xD;
             real-life evidence of the absence of recovery of clinical and radiological activity&#xD;
             after prolonged interruption of treatment.&#xD;
  &#xD;
        After 2 years of treatment, and with disease activity under control, spacing administration&#xD;
        intervals could reduce the risk of infection without reducing treatment efficacy. This would&#xD;
        facilitate the decision to maintain highly active immunotherapy over the long term. In&#xD;
        addition, this therapeutic de-escalation, by reducing the frequency of infusions and&#xD;
        associated day hospitalizations, would help to reduce treatment management costs.&#xD;
  &#xD;
        Our aim is to evaluate the non-inferiority of 12-monthly spacing of ocrelizumab infusions&#xD;
        versus the conventional 6-monthly regimen, in a population of active MS patients over 18&#xD;
        years of age who have already received 4 or more semi-annual cycles of treatment for 2 years.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">October 2027</completion_date>
    <primary_completion_date type="Anticipated">October 2027</primary_completion_date>
    <phase>Phase 3</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>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Absence of radiological disease activity at 2 years</measure>
      <time_frame>Months24</time_frame>
      <description>Percentage of patients with no new or enlarged T2 lesion &gt;3mm on cerebrospinal MRI at 24 months compared with inclusion MRI.&#xD;
  MRI readings at inclusion and M24 will be performed by an independent radiologist blinded to the treatment arm.</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">244</enrollment>
    <condition>Multiple Sclerosis</condition>
    <arm_group>
      <arm_group_label>annual ocrelizumab infusions</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>semestrial ocrelizumab infusions</arm_group_label>
      <arm_group_type>Other</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ocrelizumab Injection [Ocrevus]</intervention_name>
      <description>Semestrial administration</description>
      <arm_group_label>semestrial ocrelizumab infusions</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ocrelizumab Injection [Ocrevus]</intervention_name>
      <description>Annual administration</description>
      <arm_group_label>annual ocrelizumab infusions</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patient 18 years of age or older&#xD;
  &#xD;
            2. Presenting for a 4th semi-annual cycle of ocrelizumab (minimum)&#xD;
  &#xD;
            3. Requires follow-up MRI as part of treatment.&#xD;
  &#xD;
            4. Initial indication for ocrelizumab according to the marketing authorization (active&#xD;
               MS, RR or SP form)&#xD;
  &#xD;
            5. Absence of relapse for at least 18 months (a relapse being defined as the appearance&#xD;
               of new symptoms or worsening of existing symptoms, lasting more than 24 hours and&#xD;
               outside a period of fever or an infectious episode; notified as a validated relapse by&#xD;
               the neurologist in the patient's file, treated or not with boluses of Solu-Medrol).&#xD;
  &#xD;
            6. EDSS between 0 and 6 inclusive&#xD;
  &#xD;
            7. Having received informed information about the study and having signed a consent to&#xD;
               participate in the study&#xD;
  &#xD;
            8. French language proficiency&#xD;
  &#xD;
            9. Affiliated or beneficiary of a social insurance scheme&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Clinical forms of primary progressive MS&#xD;
  &#xD;
            2. Patients already receiving systematically spaced doses of ocrelizumab ≥ 9 months apart&#xD;
  &#xD;
            3. Contraindication to continued treatment with ocrelizumab (hypersensitivity reaction,&#xD;
               ongoing active infection, development of malignancy since previous injection,&#xD;
               development of severe immune deficiency)&#xD;
  &#xD;
            4. Planned pregnancy within 3 years&#xD;
  &#xD;
            5. Contraindication to MRI&#xD;
  &#xD;
            6. Contraindication to injection of contrast media&#xD;
  &#xD;
            7. Subject with severe or uncontrolled symptoms of renal, hepatic, hematological,&#xD;
               gastrointestinal, pulmonary, psychiatric or cardiac disease, or any uncontrolled&#xD;
               intercurrent pathology.&#xD;
  &#xD;
            8. Patient under legal protection&#xD;
  &#xD;
            9. Patients of childbearing age who do not wish to use effective contraception&#xD;
  &#xD;
           10. Pregnant or breast-feeding women&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 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>
    </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>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05999604
  org study id: CBR_2022_13
  nct id: NCT05999604
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and the
        leading cause of severe non-traumatic disability in young people, affecting 110,000 people in
        France. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has shown remarkable efficacy
        in Phase III trials on the inflammatory component of the disease, reducing the annualized
        relapse rate by 46% and the rate of new T2 lesions by 80% compared with interferon-β 1a.
  
        The use of anti-CD20 agents, including ocrelizumab, is associated with an infectious risk
        that increases with duration of exposure, part of which is due to the development of
        hypo-gammaglobulinemia in relation to cumulative dose.
  
        Several reports suggest a persistent effect of anti-CD20 drugs in MS, with no resumption of
        inflammatory activity after discontinuation:
  
          -  During the development of ocrelizumab, at the end of phase 2, after having received 3 or
             4 semi-annual cycles of ocrelizumab, a safety period with a therapeutic window of 18
             months was planned, before re-administration in the extension study. During this
             therapeutic window, the annualized relapse rate remained stable, and patients showed no
             radiological disease activity.
  
          -  Scandinavian observational studies of "off-label" use of anti-CD20 in MS provide
             real-life evidence of the absence of recovery of clinical and radiological activity
             after prolonged interruption of treatment.
  
        After 2 years of treatment, and with disease activity under control, spacing administration
        intervals could reduce the risk of infection without reducing treatment efficacy. This would
        facilitate the decision to maintain highly active immunotherapy over the long term. In
        addition, this therapeutic de-escalation, by reducing the frequency of infusions and
        associated day hospitalizations, would help to reduce treatment management costs.
  
        Our aim is to evaluate the non-inferiority of 12-monthly spacing of ocrelizumab infusions
        versus the conventional 6-monthly regimen, in a population of active MS patients over 18
        years of age who have already received 4 or more semi-annual cycles of treatment for 2 years.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  measure: Absence of radiological disease activity at 2 years
  time frame: Months24
  description: Percentage of patients with no new or enlarged T2 lesion >3mm on cerebrospinal MRI at 24 months compared with inclusion MRI.
  MRI readings at inclusion and M24 will be performed by an independent radiologist blinded to the treatment arm.
  arm group label: annual ocrelizumab infusions
  arm group type: Experimental
  arm group label: semestrial ocrelizumab infusions
  arm group type: Other
  intervention type: Drug
  intervention name: Ocrelizumab Injection [Ocrevus]
  description: Semestrial administration
  arm group label: semestrial ocrelizumab infusions
  intervention type: Drug
  intervention name: Ocrelizumab Injection [Ocrevus]
  description: Annual administration
  arm group label: annual ocrelizumab infusions
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  responsible party type: Sponsor
  mesh term: Multiple Sclerosis
  mesh term: Ocrelizumab
  sharing ipd: No