<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/NCT03784547</url>
  </required_header>
  <id_info>
    <org_study_id>RWD_Ocrelizumab LATAM</org_study_id>
    <nct_id>NCT03784547</nct_id>
  </id_info>
  <brief_title>Real-world Data of Ocrelizumab in Multiple Sclerosis in LATAM</brief_title>
  <acronym>RWD_ocre</acronym>
  <official_title>Real-world Patient Profile and Treatment Persistence of Ocrelizumab in Multiple Sclerosis: A Retrospective Analysis in Latin America</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Italiano de Buenos Aires</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Italiano de Buenos Aires</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      It has been almost 25 years since the publication of the pivotal trial results for the first&#xD;
      disease-modifying therapy (DMT) for RRMS. Currently disease modifying therapies (DMTs) for MS&#xD;
      approved by the European Medicine Agency (EMA) and Food and Drug Administration (FDA) include&#xD;
      interferon beta (IFNβ) 1-a and 1-b, glatiramer acetate (GA), mitoxantrone, natalizumab,&#xD;
      fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, daclizumab and ocrelizumab.&#xD;
      Despite evidence about ocrelizumab exist in many patients from eurpe and North America,&#xD;
      scarce real world evidence exists about epidemiolofcal aspects of patients that used&#xD;
      ocrelizumab in Latin America.&#xD;
&#xD;
      The aim of this study is therefore to evaluate patient profiles and persistence to treatment&#xD;
      during follow up in a retrospective study of patients who had been prescribed ocrelizumab for&#xD;
      the treatment of MS in Latin America (LATAM). The investigators will include MS patients that&#xD;
      received ocrelizumab in Latin America and describe epidemiological aspects and persistence to&#xD;
      treatment during the last 12 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multiple sclerosis is a chronic inflammatory disease of the CNS that leads to focal plaques&#xD;
      of primary demyelination and diffuse neurodegeneration in the grey and white matter of the&#xD;
      brain and spinal cord 1. In most patients, the disease starts with a relapsing-remitting&#xD;
      course (RRMS), which is followed several years by a secondary progressive phase (SPMS).&#xD;
      Patients with primary progressive disease (PPMS) miss the relapsing and remitting stage and&#xD;
      start with uninterrupted progression from disease onset 1-3.&#xD;
&#xD;
      It has been almost 25 years since the publication of the pivotal trial results for the first&#xD;
      disease-modifying therapy (DMT) for RRMS 4. Currently disease modifying therapies (DMTs) for&#xD;
      MS approved by the European Medicine Agency (EMA) and Food and Drug Administration (FDA)&#xD;
      include interferon beta (IFNβ) 1-a and 1-b, glatiramer acetate (GA), mitoxantrone,&#xD;
      natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, daclizumab and&#xD;
      ocrelizumab 5-7.&#xD;
&#xD;
      Ocrelizumab was approved in March 2017 for the treatment of relapsing or primary progressive&#xD;
      MS 8. A phase II trial established 600 mg intravenously every 6 months as the preferred&#xD;
      dosing schedule. Two phase III trials evaluated the efficacy of ocrelizumab in patients with&#xD;
      relapsing remitting MS, and individual and pooled analysis demonstrated a significant&#xD;
      reduction in annualized relapse rate (P &lt; 0.001 pooled), disability progression at 12 weeks (&#xD;
      P &lt; 0.001 pooled), and gadolinium-enhancing lesions on magnetic resonance imaging (MRI; P &lt;&#xD;
      0.001) 8. Patients with PPMS were evaluated in a third phase III trial, which showed a&#xD;
      significant decrease in disease progression at 12 weeks ( P = 0.03) and volume of T2-weighted&#xD;
      lesions on MRI ( P &lt; 0.001) 8. As with other monoclonal antibodies, adverse effects seen with&#xD;
      ocrelizumab were primarily infusion-related reactions and infection8. Despite much&#xD;
      information exists about efficacy and safety of ocrelizumab in phase III clinical trials,&#xD;
      scarce evidence exists regarding real world patients profile and safety.&#xD;
&#xD;
      The aim of this study is therefore to evaluate patient profiles and persistence to treatment&#xD;
      during follow up in a retrospective study of patients who had been prescribed ocrelizumab for&#xD;
      the treatment of MS in Latin America (LATAM)&#xD;
&#xD;
      Methods&#xD;
&#xD;
      Verbal/written consent from patient only if any site's Ethic Committee requests it.&#xD;
&#xD;
      Centers involved in the study will be from Mexico, Chile, Argentina Number of centers &amp;&#xD;
      patients Two centers in Argentina, two centers in Chile, and two centers in Mexico. Total: 6&#xD;
      centers and Approx 80 patients.&#xD;
&#xD;
      Study overview Patients that accept to participate and fulfill all inclusion criteria and&#xD;
      none exclusion criteria will be included. All information will be extracted from the medical&#xD;
      charts Data Source Information related to the study population will be extracted from the&#xD;
      patient medical chart review (secondary data use) and will cover a period up to protocol&#xD;
      regulatory approval. Patient identity will be coded and anonymized in the study data base so&#xD;
      only each investigator will know the identity of each patient. Local legislation regarding&#xD;
      patient data protection will be followed strictly in this study. All study data will be&#xD;
      entered in a predefined electronic Case Report Form (CRF).&#xD;
&#xD;
      This is an NIS involving the use of secondary data and the reporting of adverse reactions in&#xD;
      the form of ICSRs is not required. The study will not extract safety information.&#xD;
&#xD;
      Storage and data analysis&#xD;
&#xD;
      Once the patient is identified and consented to participate (if needed based on local&#xD;
      regulatory aspects), data from patient's chart will be transferred into the specifically&#xD;
      designed platform. The platform on which variables will be transferred, will be on a web&#xD;
      platform with restricted access by user and password specific to each researcher. When&#xD;
      sharing the data, it will be anonymized and only data related to the demographics and clinic&#xD;
      will be accessible, and patient data such as name, surname and ID will not be visible to&#xD;
      analysts if it is loaded.&#xD;
&#xD;
      Data protection&#xD;
&#xD;
      The regulatory requirements and protection of personal data must be completed according to&#xD;
      the regulations corresponding to each participant.&#xD;
&#xD;
      Each researcher in the study should explain in detail to each potential participant the&#xD;
      record consists. Every patient who wishes to participate in the project must consent,&#xD;
      according to each regulation, authorizing that their information, codified and anonymized, be&#xD;
      shared with other records for analysis and communication.&#xD;
&#xD;
      An institutional ethics committee must approve the registration or declare that it is exempt&#xD;
      from the need for approval as well as its informed consent (IC).&#xD;
&#xD;
      The data will be uploaded by the physician of each participating center. The different&#xD;
      variables will be obtained from the daily clinical practice of each professional.&#xD;
&#xD;
      Patient Confidentiality As mentioned in the previous point, the patient's name, address, date&#xD;
      of birth, ID or telephone number will only be left in the personal registry and at the moment&#xD;
      of sharing the registration to the central registry will not be entered. The records will&#xD;
      then be identified by a unique code generated by the initials of the IP and the registration&#xD;
      number of that patient.&#xD;
&#xD;
      Each registry should include baseline clinical and demographic data as well as the study&#xD;
      project data.&#xD;
&#xD;
      At all times, the protection of the patient's identity and data will be observed in&#xD;
      accordance with the legal regulations in force national law of protection of personal data&#xD;
      25.326 (Habeas Data), in accordance with the international legislation on registration of&#xD;
      diseases and protection of personal data and private, according to the 18th World Medical&#xD;
      Assembly of Helsinki (1964) when applicable. The right to non-participation in the study will&#xD;
      be respected always without this implying in any case any type of discrimination,&#xD;
      differential treatment or mistreatment towards the patient.&#xD;
&#xD;
      This is a retrospective observational study, which does not plan any type of intervention or&#xD;
      differential treatment in patients included or excluded.&#xD;
&#xD;
      Statistical analysis plan This is descriptive study and sample size is not based on&#xD;
      statistical considerations. A descriptive analysis is the main objective of the study&#xD;
      regarding demographic, clinical aspects, disease activity and persistence to treatment of&#xD;
      patients that received ocrelizumab to treat their MS disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Anticipated">September 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2019</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients discontinuing the treatment with ocrelizumab in the last 12 months after inclusion</measure>
    <time_frame>12 months</time_frame>
    <description>To describe the number of patients that discontinue the use of ocrelizumab during the last 12 months</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Multiple sclerosis phenotype</measure>
    <time_frame>12 months</time_frame>
    <description>to describe the MS phenotype of patients that received ocrelizumab in LATAM</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gender</measure>
    <time_frame>12 months</time_frame>
    <description>to describe the gender of patients that received ocrelizumab in LATAM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Age at study entry</measure>
    <time_frame>12 months</time_frame>
    <description>To describe the age of patients that received ocrelizumab at study entry</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>multiple sclerosis patients</arm_group_label>
    <description>multiple sclerosis patients receiving ocrelizumab 600 mg endovenous every 6 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ocrelizumab</intervention_name>
    <description>already described</description>
    <arm_group_label>multiple sclerosis patients</arm_group_label>
    <other_name>no other</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients must meet the following inclusion criteria:&#xD;
&#xD;
        MS patients who received ocrelizumab to treat their disease&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - multiple sclerosis patients that received ocrelizumab&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Juan I Rojas, MD</last_name>
    <phone>+5491169001957</phone>
    <email>juan.rojas@hiba.org.ar</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Edgardo Cristiano, MD</last_name>
    <phone>00541149590200</phone>
    <email>cristiano.edgardo@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Juan Ignacio Rojas</name>
      <address>
        <city>Buenos Aires</city>
        <zip>1453</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Juan I Rojas</last_name>
      <phone>91169001957</phone>
      <email>juan.rojas@hiba.org.ar</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Juan Ignacio Rojas</name>
      <address>
        <city>Buenos Aires</city>
        <zip>1453</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Juan Ignacio Rojas</name>
      <address>
        <city>Buenos Aires</city>
        <zip>1453</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Juan I Rojas</last_name>
      <phone>+5491169001957</phone>
      <email>rojasjuanignacio@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Edgar Carnero, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Edgard Carnero</name>
      <address>
        <city>Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>August 7, 2019</last_update_submitted>
  <last_update_submitted_qc>August 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>multiple sclerosis</keyword>
  <keyword>Latin america</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>
  <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>


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/NCT03784547
org study id: RWD_Ocrelizumab LATAM
nct id: NCT03784547
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
It has been almost 25 years since the publication of the pivotal trial results for the first
      disease-modifying therapy (DMT) for RRMS. Currently disease modifying therapies (DMTs) for MS
      approved by the European Medicine Agency (EMA) and Food and Drug Administration (FDA) include
      interferon beta (IFNβ) 1-a and 1-b, glatiramer acetate (GA), mitoxantrone, natalizumab,
      fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, daclizumab and ocrelizumab.
      Despite evidence about ocrelizumab exist in many patients from eurpe and North America,
      scarce real world evidence exists about epidemiolofcal aspects of patients that used
      ocrelizumab in Latin America.

      The aim of this study is therefore to evaluate patient profiles and persistence to treatment
      during follow up in a retrospective study of patients who had been prescribed ocrelizumab for
      the treatment of MS in Latin America (LATAM). The investigators will include MS patients that
      received ocrelizumab in Latin America and describe epidemiological aspects and persistence to
      treatment during the last 12 months.
Multiple sclerosis is a chronic inflammatory disease of the CNS that leads to focal plaques
      of primary demyelination and diffuse neurodegeneration in the grey and white matter of the
      brain and spinal cord 1. In most patients, the disease starts with a relapsing-remitting
      course (RRMS), which is followed several years by a secondary progressive phase (SPMS).
      Patients with primary progressive disease (PPMS) miss the relapsing and remitting stage and
      start with uninterrupted progression from disease onset 1-3.

      It has been almost 25 years since the publication of the pivotal trial results for the first
      disease-modifying therapy (DMT) for RRMS 4. Currently disease modifying therapies (DMTs) for
      MS approved by the European Medicine Agency (EMA) and Food and Drug Administration (FDA)
      include interferon beta (IFNβ) 1-a and 1-b, glatiramer acetate (GA), mitoxantrone,
      natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, daclizumab and
      ocrelizumab 5-7.

      Ocrelizumab was approved in March 2017 for the treatment of relapsing or primary progressive
      MS 8. A phase II trial established 600 mg intravenously every 6 months as the preferred
      dosing schedule. Two phase III trials evaluated the efficacy of ocrelizumab in patients with
      relapsing remitting MS, and individual and pooled analysis demonstrated a significant
      reduction in annualized relapse rate (P < 0.001 pooled), disability progression at 12 weeks (
      P < 0.001 pooled), and gadolinium-enhancing lesions on magnetic resonance imaging (MRI; P <
      0.001) 8. Patients with PPMS were evaluated in a third phase III trial, which showed a
      significant decrease in disease progression at 12 weeks ( P = 0.03) and volume of T2-weighted
      lesions on MRI ( P < 0.001) 8. As with other monoclonal antibodies, adverse effects seen with
      ocrelizumab were primarily infusion-related reactions and infection8. Despite much
      information exists about efficacy and safety of ocrelizumab in phase III clinical trials,
      scarce evidence exists regarding real world patients profile and safety.

      The aim of this study is therefore to evaluate patient profiles and persistence to treatment
      during follow up in a retrospective study of patients who had been prescribed ocrelizumab for
      the treatment of MS in Latin America (LATAM)

      Methods

      Verbal/written consent from patient only if any site's Ethic Committee requests it.

      Centers involved in the study will be from Mexico, Chile, Argentina Number of centers &
      patients Two centers in Argentina, two centers in Chile, and two centers in Mexico. Total: 6
      centers and Approx 80 patients.

      Study overview Patients that accept to participate and fulfill all inclusion criteria and
      none exclusion criteria will be included. All information will be extracted from the medical
      charts Data Source Information related to the study population will be extracted from the
      patient medical chart review (secondary data use) and will cover a period up to protocol
      regulatory approval. Patient identity will be coded and anonymized in the study data base so
      only each investigator will know the identity of each patient. Local legislation regarding
      patient data protection will be followed strictly in this study. All study data will be
      entered in a predefined electronic Case Report Form (CRF).

      This is an NIS involving the use of secondary data and the reporting of adverse reactions in
      the form of ICSRs is not required. The study will not extract safety information.

      Storage and data analysis

      Once the patient is identified and consented to participate (if needed based on local
      regulatory aspects), data from patient's chart will be transferred into the specifically
      designed platform. The platform on which variables will be transferred, will be on a web
      platform with restricted access by user and password specific to each researcher. When
      sharing the data, it will be anonymized and only data related to the demographics and clinic
      will be accessible, and patient data such as name, surname and ID will not be visible to
      analysts if it is loaded.

      Data protection

      The regulatory requirements and protection of personal data must be completed according to
      the regulations corresponding to each participant.

      Each researcher in the study should explain in detail to each potential participant the
      record consists. Every patient who wishes to participate in the project must consent,
      according to each regulation, authorizing that their information, codified and anonymized, be
      shared with other records for analysis and communication.

      An institutional ethics committee must approve the registration or declare that it is exempt
      from the need for approval as well as its informed consent (IC).

      The data will be uploaded by the physician of each participating center. The different
      variables will be obtained from the daily clinical practice of each professional.

      Patient Confidentiality As mentioned in the previous point, the patient's name, address, date
      of birth, ID or telephone number will only be left in the personal registry and at the moment
      of sharing the registration to the central registry will not be entered. The records will
      then be identified by a unique code generated by the initials of the IP and the registration
      number of that patient.

      Each registry should include baseline clinical and demographic data as well as the study
      project data.

      At all times, the protection of the patient's identity and data will be observed in
      accordance with the legal regulations in force national law of protection of personal data
      25.326 (Habeas Data), in accordance with the international legislation on registration of
      diseases and protection of personal data and private, according to the 18th World Medical
      Assembly of Helsinki (1964) when applicable. The right to non-participation in the study will
      be respected always without this implying in any case any type of discrimination,
      differential treatment or mistreatment towards the patient.

      This is a retrospective observational study, which does not plan any type of intervention or
      differential treatment in patients included or excluded.

      Statistical analysis plan This is descriptive study and sample size is not based on
      statistical considerations. A descriptive analysis is the main objective of the study
      regarding demographic, clinical aspects, disease activity and persistence to treatment of
      patients that received ocrelizumab to treat their MS disease.
observational model: Cohort
time perspective: Retrospective
measure: Proportion of patients discontinuing the treatment with ocrelizumab in the last 12 months after inclusion
time frame: 12 months
description: To describe the number of patients that discontinue the use of ocrelizumab during the last 12 months
measure: Multiple sclerosis phenotype
time frame: 12 months
description: to describe the MS phenotype of patients that received ocrelizumab in LATAM
measure: Gender
time frame: 12 months
description: to describe the gender of patients that received ocrelizumab in LATAM
measure: Age at study entry
time frame: 12 months
description: To describe the age of patients that received ocrelizumab at study entry
arm group label: multiple sclerosis patients
description: multiple sclerosis patients receiving ocrelizumab 600 mg endovenous every 6 months
intervention type: Drug
intervention name: Ocrelizumab
description: already described
arm group label: multiple sclerosis patients
other name: no other
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Juan I Rojas, MD
phone: +5491169001957
email: juan.rojas@hiba.org.ar
last name: Edgardo Cristiano, MD
phone: 00541149590200
email: cristiano.edgardo@gmail.com
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Completed
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Completed
country: Argentina
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis
mesh term: Ocrelizumab
sharing ipd: No