<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/NCT04480853</url>
  </required_header>
  <id_info>
    <org_study_id>CFTY720DTW03</org_study_id>
    <nct_id>NCT04480853</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy Study of Fingolimod in Taiwanese Adults (≥ 20years) With Relapsing Remitting Multiple Sclerosis</brief_title>
  <acronym>SPRING</acronym>
  <official_title>A 12-month, Prospective, Multi-center Post-authorization Commitment (PAC) Study Monitoring Safety in Adult Patients With Relapsing-remitting Multiple Sclerosis Newly Initiated on Gilenya (Fingolimod) in Taiwan (SPRING)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</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 purpose of the study is to describe the safety profile of fingolimod in the Taiwanese&#xD;
      multiple sclerosis population. This study aims to collect the safety data in patients newly&#xD;
      initiated on fingolimod for one year.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 12-month, prospective, interventional, multi-center study to monitor safety in&#xD;
      adult patients with relapsing-remitting multiple sclerosis (RRMS) in Taiwan who based on&#xD;
      local practice are newly starting fingolimod at the time of study entry.&#xD;
&#xD;
      Thirty-four patients will be included in this study in line with the study inclusion and&#xD;
      exclusion criteria. After entering this study, the participants will continue to be treated&#xD;
      for MS based on local practice. The patient will be taking fingolimod 0.5mg per day.&#xD;
      Protocol-mandated procedures and visits for safety data collection will be conducted in&#xD;
      addition to the required examinations according to the clinical practice.&#xD;
&#xD;
      If a patient experienced an interruption of fingolimod treatment that requires a&#xD;
      re-evaluation of FDO, the patient will be discontinued from the study. If the treatment&#xD;
      interruption does not require a FDO when re-starting fingolimod, the patient can continue to&#xD;
      participate in this study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 12, 2020</start_date>
  <completion_date type="Anticipated">February 28, 2025</completion_date>
  <primary_completion_date type="Anticipated">February 28, 2025</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Adverse Events of Special Interest(AESI)</measure>
    <time_frame>First Dose Observation on the first day of taking findolimod</time_frame>
    <description>The adverse events of special interest (AESI) include bradycardia and Grade 2 or higher AV block during First Dose Observation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Adverse Events of Special Interest (AESI)</measure>
    <time_frame>Baseline up to 12 months</time_frame>
    <description>The adverse events of special interest (AESI) include macular edema, abnormal liver function(ALT, AST or GGT &gt; 5x upper normal limit), and severe lymphocytopenia(lymphocyte &lt; 200 cells/μL).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annualized relapse reate (ARR)</measure>
    <time_frame>Baseline up to 12 months</time_frame>
    <description>The ARR will be calculated as total number of relapses experienced divided by total number of days of follow-up, and the ratio multiplied by 365. For patients withdraw from the study or switch to an alternative MS therapy prior to 12 month, the total number of days in study is defined as the number of days from baseline to the last date in study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of Pulse (beats/min)</measure>
    <time_frame>Baseline up to 12 months</time_frame>
    <description>Pulse (beats/min - bpm) data will be summarized as descriptive statistics for change from baseline value (both for the period 6-hours post first dose and for further visit assessments). The frequency and percentage of notable vital sign abnormalities will be summarized. Notable criteria for pulse is &gt; 120bpm or Increase of ≥15 bpm from baseline Or &lt; 50bpm or Decrease of ≥15 bpm from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of blood pressure (mmHg)</measure>
    <time_frame>Baseline up to 12 months</time_frame>
    <description>Blood pressure(BP)(mmHg) data will be summarized as descriptive statistics for change from baseline value (both for the period 6-hours post first dose and for further visit assessments). The frequency and percentage of notable vital sign abnormalities will be summarized. Notable criteria for systolic BP is ≥160 mm Hg or Increase of ≥20 mm Hg from baseline Or ≤ 90 mm Hg or Decrease of ≥ 20 mm Hg from baseline. Notable criteria for diastolic BP is ≥ 100 mmHg or Increase of ≥ 15 mm Hg from baseline Or ≤ 50 mmHg or Decrease of ≥ 15 mm Hg from baseline.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Fingolimod</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open label Fingolimod 0.5 mg capsule taken once daily, oral.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fingolimod</intervention_name>
    <description>Fingolimod 0.5 mg QD, oral</description>
    <arm_group_label>Fingolimod</arm_group_label>
    <other_name>FTY720</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -Patients with relapsing-remitting multiple sclerosis that are fingolimod treatment naive&#xD;
        at the time of study entry and are newly starting fingolimod based on physician judgement&#xD;
        and according to Taiwan's fingolimod package insert (version TWI-090420)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with the diagnosis of neuromyelitis optica.&#xD;
&#xD;
          -  Patients who are being treated with any investigational drug at the time of study&#xD;
             entry.&#xD;
&#xD;
          -  In the last 6 months experienced myocardial infarction, unstable angina, stroke,&#xD;
             transient ischemic attack, decompensated heart failure requiring hospitalization or&#xD;
             Class III/IV heart failure&#xD;
&#xD;
          -  A history or presence of Mobitz Type II second-degree or third-degree atrioventricular&#xD;
             block or sick sinus syndrome, unless patient has a functioning pacemaker&#xD;
&#xD;
          -  A baseline QTc interval ≥ 500 msec&#xD;
&#xD;
          -  Cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III&#xD;
             anti-arrhythmic drugs&#xD;
&#xD;
          -  Patient with known immune deficiency, increased risk of opportunistic infection,&#xD;
             severe active infection or chronic active infection.&#xD;
&#xD;
          -  Patients with severe active malignancies, except for basal cell epithelioma&#xD;
&#xD;
          -  Patients with severe hepatic insufficiency&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women or women of childbearing potential unless on&#xD;
             contraception&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Novartis Pharmaceuticals</last_name>
    <phone>+41613241111</phone>
    <email>novartis.email@novartis.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Novartis Pharmaceuticals</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kaoshiung</city>
        <zip>83301</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taichung</city>
        <zip>40705</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tainan</city>
        <zip>70403</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>11220</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taoyuan</city>
        <zip>33305</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>July 13, 2023</last_update_submitted>
  <last_update_submitted_qc>July 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fingolimod</keyword>
  <keyword>Multiple sclerosis</keyword>
  <keyword>Relapsing-remitting multiple sclerosis</keyword>
  <keyword>Relapsing-remitting</keyword>
  <keyword>Post-authorization study</keyword>
  <keyword>Adult</keyword>
  <keyword>MS</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fingolimod Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </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/NCT04480853
org study id: CFTY720DTW03
nct id: NCT04480853
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of the study is to describe the safety profile of fingolimod in the Taiwanese
      multiple sclerosis population. This study aims to collect the safety data in patients newly
      initiated on fingolimod for one year.
This is a 12-month, prospective, interventional, multi-center study to monitor safety in
      adult patients with relapsing-remitting multiple sclerosis (RRMS) in Taiwan who based on
      local practice are newly starting fingolimod at the time of study entry.

      Thirty-four patients will be included in this study in line with the study inclusion and
      exclusion criteria. After entering this study, the participants will continue to be treated
      for MS based on local practice. The patient will be taking fingolimod 0.5mg per day.
      Protocol-mandated procedures and visits for safety data collection will be conducted in
      addition to the required examinations according to the clinical practice.

      If a patient experienced an interruption of fingolimod treatment that requires a
      re-evaluation of FDO, the patient will be discontinued from the study. If the treatment
      interruption does not require a FDO when re-starting fingolimod, the patient can continue to
      participate in this study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Adverse Events of Special Interest(AESI)
time frame: First Dose Observation on the first day of taking findolimod
description: The adverse events of special interest (AESI) include bradycardia and Grade 2 or higher AV block during First Dose Observation.
measure: Number of Adverse Events of Special Interest (AESI)
time frame: Baseline up to 12 months
description: The adverse events of special interest (AESI) include macular edema, abnormal liver function(ALT, AST or GGT > 5x upper normal limit), and severe lymphocytopenia(lymphocyte < 200 cells/μL).
measure: Annualized relapse reate (ARR)
time frame: Baseline up to 12 months
description: The ARR will be calculated as total number of relapses experienced divided by total number of days of follow-up, and the ratio multiplied by 365. For patients withdraw from the study or switch to an alternative MS therapy prior to 12 month, the total number of days in study is defined as the number of days from baseline to the last date in study.
measure: Change from baseline of Pulse (beats/min)
time frame: Baseline up to 12 months
description: Pulse (beats/min - bpm) data will be summarized as descriptive statistics for change from baseline value (both for the period 6-hours post first dose and for further visit assessments). The frequency and percentage of notable vital sign abnormalities will be summarized. Notable criteria for pulse is > 120bpm or Increase of ≥15 bpm from baseline Or < 50bpm or Decrease of ≥15 bpm from baseline
measure: Change from baseline of blood pressure (mmHg)
time frame: Baseline up to 12 months
description: Blood pressure(BP)(mmHg) data will be summarized as descriptive statistics for change from baseline value (both for the period 6-hours post first dose and for further visit assessments). The frequency and percentage of notable vital sign abnormalities will be summarized. Notable criteria for systolic BP is ≥160 mm Hg or Increase of ≥20 mm Hg from baseline Or ≤ 90 mm Hg or Decrease of ≥ 20 mm Hg from baseline. Notable criteria for diastolic BP is ≥ 100 mmHg or Increase of ≥ 15 mm Hg from baseline Or ≤ 50 mmHg or Decrease of ≥ 15 mm Hg from baseline.
arm group label: Fingolimod
arm group type: Experimental
description: Open label Fingolimod 0.5 mg capsule taken once daily, oral.
intervention type: Drug
intervention name: Fingolimod
description: Fingolimod 0.5 mg QD, oral
arm group label: Fingolimod
other name: FTY720
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
last name: Novartis Pharmaceuticals
phone: +41613241111
email: novartis.email@novartis.com
last name: Novartis Pharmaceuticals
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: Taiwan
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Relapsing-Remitting
mesh term: Sclerosis
mesh term: Fingolimod Hydrochloride
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com