<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/NCT01706107</url>
  </required_header>
  <id_info>
    <org_study_id>CAN-TYS-12-10333</org_study_id>
    <nct_id>NCT01706107</nct_id>
  </id_info>
  <brief_title>Canadian Multicenter Observational Study of Tysabri in Early Relapsing Remitting Multiple Sclerosis Participants</brief_title>
  <acronym>COSTAN</acronym>
  <official_title>Canadian Multicenter Observational Study of Tysabri in Early Relapsing Remitting Multiple Sclerosis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biogen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biogen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study is to evaluate the impact of early treatment with Tysabri&#xD;
      in Relapsing Remitting Multiple Sclerosis (RRMS) participants on their quality of life (QoL)&#xD;
      as measured by Multiple Sclerosis Impact Scale-29 (MSIS-29) over 2 years. The secondary&#xD;
      objectives of the study are: to evaluate the impact of early treatment with Tysabri in RRMS&#xD;
      participants over 2 years on the following: annualized relapse rate (ARR), Expanded&#xD;
      Disability Status Scale (EDSS), work productivity, quality of life (QoL) by EuroQol&#xD;
      5-Dimension questionnaire (EQ-5D), QoL by Subject Global Assessment of Wellbeing visual&#xD;
      analog scale (VAS) and to evaluate clinical disease-free status (relapses, EDSS) over 2&#xD;
      years.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to on-going enrollment challenges&#xD;
  </why_stopped>
  <start_date>April 2012</start_date>
  <completion_date type="Anticipated">January 2018</completion_date>
  <primary_completion_date type="Anticipated">October 2017</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>Change from Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29)</measure>
    <time_frame>Baseline, Months 12 and 24</time_frame>
    <description>The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a patient-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a patient's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Annualized Relapse Rate</measure>
    <time_frame>Baseline, Months 12 and 24</time_frame>
    <description>A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Expanded Disability Status Scale (EDSS)</measure>
    <time_frame>Baseline, Months 12 and 24</time_frame>
    <description>The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Work Productivity and Activity Impairment</measure>
    <time_frame>Baseline, Months 12 and 24</time_frame>
    <description>The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in EuroQol 5-Dimension (EQ-5D)</measure>
    <time_frame>Baseline, Months 12 and 24</time_frame>
    <description>The EQ-5D is a self-administered questionnaire consisting of 5 sets of 3 questions pertaining to specific health states (i.e., mobility, self-care, pain, usual activities, anxiety), and a visual analog scale that records the respondent's self-rated health from 0 (worst imaginable health state) to 100 (best imaginable health state).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Patient Global Assessment of Wellbeing Visual Analog Scale</measure>
    <time_frame>Baseline, Months 12 and 24</time_frame>
    <description>Patient Global Assessment of Wellbeing measures quality of life on a 100 mm Visual Analog Scale (VAS) where 0 is the worst imaginable health state and 100 is the best imaginable health state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with Clinical Disease-Free Status</measure>
    <time_frame>Baseline, Months 12 and 24</time_frame>
    <description>Freedom from clinical disease activity is defined as the percentage of participants with no relapse and no EDSS progression, defined as a 1-point change from baseline. EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.</description>
  </secondary_outcome>
  <enrollment type="Actual">73</enrollment>
  <condition>Relapsing-Remitting Multiple Sclerosis</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who choose to participate in the study will receive a thorough description of the&#xD;
        study protocol and an informed consent document describing the study and the risks and&#xD;
        benefits of participating. Recruitment will continue until approximately 150 patients have&#xD;
        been enrolled in the study at approximately 15 sites across Canada.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Ability to understand the purpose and risks of the study and provide signed and dated&#xD;
             informed consent.&#xD;
&#xD;
          -  Documented diagnosis of Relapsing Multiple Sclerosis (McDonald 2010 Criteria).&#xD;
&#xD;
          -  Must have an Expanded Disability Status Scale (EDSS) score from 0 to 4.0, inclusive.&#xD;
&#xD;
          -  Must satisfy the approved therapeutic indications for Tysabri as per Product&#xD;
             Monograph.&#xD;
&#xD;
          -  Must either be treatment naïve or have been treated with disease modifying therapy&#xD;
             DMT(s) (such as, but not limited to, Avonex, Betaseron, Rebif, Copaxone, Extavia,&#xD;
             Tecfidera and/or Gilenya) for ≤5 years total prior to date of informed consent.&#xD;
&#xD;
          -  Decision to treat with Tysabri must precede enrollment.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Any prior treatment with Tysabri.&#xD;
&#xD;
          -  Contraindications to treatment with Tysabri as described in the Product Monograph.&#xD;
&#xD;
          -  History of progressive multifocal leukoencephalopathy (PML) or other opportunistic&#xD;
             infections, or an increased risk for such infections.&#xD;
&#xD;
          -  History of diagnosis of Primary Progressive Multiple Sclerosis [PPMS] and/or Secondary&#xD;
             Progressive Multiple Sclerosis [SPMS].&#xD;
&#xD;
          -  Receiving immunomodulatory or immunosuppressive therapy.&#xD;
&#xD;
          -  Prior history of immunosuppressive use (mitoxantrone, azathioprine, methotrexate,&#xD;
             cyclophosphamide, mycophenolate, cladribine, rituximab).&#xD;
&#xD;
          -  Immunocompromised at the time of enrollment.&#xD;
&#xD;
          -  Known active malignancies (subjects with cutaneous basal cell carcinoma that has been&#xD;
             completely excised prior to study entry remain eligible).&#xD;
&#xD;
          -  Women breastfeeding, pregnant, or planning to become pregnant; women who are not&#xD;
             post-menopausal or surgically sterile who are unwilling to practice contraception.&#xD;
&#xD;
          -  Inability to comply with study requirements.&#xD;
&#xD;
        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Biogen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vancouver Island Health Authority</name>
      <address>
        <city>Victoria</city>
        <state>British Columbia</state>
        <zip>V8R 1J8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint John Regional Hospital</name>
      <address>
        <city>Saint John</city>
        <state>New Brunswick</state>
        <zip>E2L 4L2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dalhousie MS Research Unit</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 4K4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cape Breton Regional Hospital</name>
      <address>
        <city>Sydney</city>
        <state>Nova Scotia</state>
        <zip>B1P 1P3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique Neuro-Outaouais</name>
      <address>
        <city>Gatineau</city>
        <state>Quebec</state>
        <zip>J9J 0A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neuro Rive-Sud</name>
      <address>
        <city>Greenfield Park</city>
        <state>Quebec</state>
        <zip>J4V 2J2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHUM - Hopital Notre Dame</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2L 4M1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University - MNI</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3A 2B4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHUS - Hopital Fleurimont</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H 5N4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <removed_countries>
    <country>Switzerland</country>
  </removed_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>October 11, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2012</study_first_posted>
  <last_update_submitted>January 8, 2016</last_update_submitted>
  <last_update_submitted_qc>January 8, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 12, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Quality of life</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Relapsing-Remitting</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/NCT01706107
org study id: CAN-TYS-12-10333
nct id: NCT01706107
lead sponsor: 
has dmc: No
The primary objective of the study is to evaluate the impact of early treatment with Tysabri
      in Relapsing Remitting Multiple Sclerosis (RRMS) participants on their quality of life (QoL)
      as measured by Multiple Sclerosis Impact Scale-29 (MSIS-29) over 2 years. The secondary
      objectives of the study are: to evaluate the impact of early treatment with Tysabri in RRMS
      participants over 2 years on the following: annualized relapse rate (ARR), Expanded
      Disability Status Scale (EDSS), work productivity, quality of life (QoL) by EuroQol
      5-Dimension questionnaire (EQ-5D), QoL by Subject Global Assessment of Wellbeing visual
      analog scale (VAS) and to evaluate clinical disease-free status (relapses, EDSS) over 2
      years.
observational model: Cohort
time perspective: Prospective
measure: Change from Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29)
time frame: Baseline, Months 12 and 24
description: The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a patient-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a patient's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 to 100, where high scores indicate worse health.
measure: Change from Baseline in Annualized Relapse Rate
time frame: Baseline, Months 12 and 24
description: A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement.
measure: Change from Baseline in Expanded Disability Status Scale (EDSS)
time frame: Baseline, Months 12 and 24
description: The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.
measure: Change from Baseline in Work Productivity and Activity Impairment
time frame: Baseline, Months 12 and 24
description: The Work Productivity and Activity Impairment (WPAI) questionnaire is a validated instrument to measure impairments in work and activities. The WPAI yields four types of scores: 1. Absenteeism (work time missed) 2. Presenteesism (impairment at work / reduced on-the-job effectiveness) 3. Work productivity loss (overall work impairment / absenteeism plus presenteeism) 4. Activity Impairment. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
measure: Change from Baseline in EuroQol 5-Dimension (EQ-5D)
time frame: Baseline, Months 12 and 24
description: The EQ-5D is a self-administered questionnaire consisting of 5 sets of 3 questions pertaining to specific health states (i.e., mobility, self-care, pain, usual activities, anxiety), and a visual analog scale that records the respondent's self-rated health from 0 (worst imaginable health state) to 100 (best imaginable health state).
measure: Change from Baseline in Patient Global Assessment of Wellbeing Visual Analog Scale
time frame: Baseline, Months 12 and 24
description: Patient Global Assessment of Wellbeing measures quality of life on a 100 mm Visual Analog Scale (VAS) where 0 is the worst imaginable health state and 100 is the best imaginable health state.
measure: Percentage of participants with Clinical Disease-Free Status
time frame: Baseline, Months 12 and 24
description: Freedom from clinical disease activity is defined as the percentage of participants with no relapse and no EDSS progression, defined as a 1-point change from baseline. EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Biogen
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: Switzerland
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Relapsing-Remitting
mesh term: Sclerosis