<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/NCT03237260</url>
  </required_header>
  <id_info>
    <org_study_id>825665</org_study_id>
    <nct_id>NCT03237260</nct_id>
  </id_info>
  <brief_title>An Open Label Single-arm Phase 4 Study of Vedolizumab in Subjects With Newly Diagnosed Active Ulcerative Colitis</brief_title>
  <official_title>An Open Label Single-arm Phase 4 Study of Vedolizumab in Subjects With Newly Diagnosed Active Ulcerative Colitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Corporal Michael J. Crescenz VA Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to determine whether starting the drug vedolizumab&#xD;
      earlier than its FDA approved use can lead to better control of UC then using older drugs&#xD;
      that we have historically used to treat UC. Vedolizumab is FDA-approved to be used after&#xD;
      initial Corticosteroid treatments have failed or other UC treatments have failed. We will&#xD;
      study if using vedolizumab as an early treatment for your UC will allow you to get off&#xD;
      corticosteroids and prevent UC from worsening and requiring surgery.&#xD;
&#xD;
      Vedolizumab is given intravenously initially every 2 weeks and then every 8 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Based upon our published data, 53% of patients who require CS at the time of diagnosis of UC&#xD;
      will be in CS free remission in the absence of colectomy by the end of 52 weeks. Early&#xD;
      corticosteroids requirement after the diagnosis of ulcerative colitis diagnosis can predict a&#xD;
      more severe long-term course of the disease. This work formed the basis of this research&#xD;
      project. We had postulated that patients requiring steroids early in the course of their&#xD;
      disease had worse prognosis than those who did not and should be treated more aggressively&#xD;
      early in the course of their disease to prevent future complications like colectomy.&#xD;
&#xD;
      The current standard of care for treatment of UC in the VA is as follows:&#xD;
&#xD;
      At the time of diagnosis all the patients are started on a 5-ASA compound. Those patients who&#xD;
      have very severe disease are concomitantly started on steroids. If they are very sick they&#xD;
      are concomitantly started on an anti-TNF compound also with the goal of tapering them off&#xD;
      steroids. Based upon response to therapy medications are adjusted. If there is no relief with&#xD;
      5-ASA compounds they can be started on steroids. For those on steroids and who cannot be&#xD;
      weaned off steroids or are requiring multiple courses of steroids, they will have their&#xD;
      therapy advanced to an anti-TNF or vedoluzimab. For those failing an anti-TNF they can be&#xD;
      shifted to vedoluzimab. Thus, at the VA, vedoluzimab is available at the VA thru the&#xD;
      non-formulary process. It is restricted to GI as 3rd line agent for UC. That is, it is used&#xD;
      after oral agents fail and after anti-TNF agents (Humira® or Remicade®). The indications for&#xD;
      Vedoluzimab use in the VA are as follows with regard to failure:&#xD;
&#xD;
      The patient has had adequate therapeutic trials of ONE of the following treatments, unless&#xD;
      the patient has a contraindication, risk factor for serious adverse event*, or intolerance to&#xD;
      the agent(s):&#xD;
&#xD;
      Criterion 1 is an option with or without therapeutic drug monitoring.)&#xD;
&#xD;
      A TNFI and an antimetabolite immunomodulator, separately or in combination. OR An initial and&#xD;
      second TNFI, if therapeutic drug monitoring after secondary nonresponse to TNFI therapy&#xD;
      indicates high titers of anti-TNFI antibodies.&#xD;
&#xD;
      OR&#xD;
&#xD;
      A TNFI, when either of the following apply:&#xD;
&#xD;
      Induction therapy with an agent from a different biologic class is needed to treat an&#xD;
      inadequate response (with confirmed active inflammation / persistent disease) following TNFI&#xD;
      induction therapy (i.e., primary nonresponse) and therapeutic drug monitoring shows&#xD;
      therapeutic or high trough TNFI serum concentrations.&#xD;
&#xD;
      The patient lost response (i.e., secondary nonresponse not due to adverse reaction) to the&#xD;
      initial TNFI in association with therapeutic or high trough TNFI serum concentration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No patient accrual&#xD;
  </why_stopped>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">February 1, 2019</completion_date>
  <primary_completion_date type="Actual">February 1, 2019</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>corticosteroid free remission as well as the absence of a colectomy</measure>
    <time_frame>52 weeks</time_frame>
    <description>corticosteroid free remission as well as the absence of a colectomy</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>Vedolizumab 300mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>vedolizumab open label</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vedolizumab</intervention_name>
    <description>Initiation: 300 mg at week 0, 2 and 6. Maintenance: Every 8 weeks after the sixth week at a fixed dose of 300 mg</description>
    <arm_group_label>Vedolizumab 300mg</arm_group_label>
    <other_name>entyvio</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newly diagnosed active ulcerative colitis, defined as a Mayo Clinic score of 6 to 12&#xD;
&#xD;
          -  Prior Sigmoidoscopy sub score of at least 2, and disease that extended 15 cm or more&#xD;
             from the anal verge&#xD;
&#xD;
          -  Must have required CS for treatment of their symptoms within 2 weeks of diagnosis and&#xD;
             have not reached symptom adequate response and they still have moderate to severe&#xD;
             disease, indicated by a Mayo score 6 - 12&#xD;
&#xD;
          -  In subjects that enroll and are eligible to continue in the study, study drug needs to&#xD;
             be started within 3 months of the subject starting corticosteroids&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently treated with either anti-TNF therapy, immunomodulators or methotrexate due&#xD;
             to the severity of their condition, making them not appropriate for vedolizumab&#xD;
&#xD;
          -  Toxic megacolon, abdominal abscess, symptomatic colonic stricture, an increased risk&#xD;
             of infectious complications&#xD;
&#xD;
          -  An anticipated requirement for major surgery, colonic dysplasia or adenomas and&#xD;
             malignant neoplasms&#xD;
&#xD;
          -  Neurological disorders&#xD;
&#xD;
          -  Pregnant or lactating females&#xD;
&#xD;
          -  Clinical response to steroids prior to starting study drug&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nabeel Khan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistant Professor of Clinical Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Corporal Michael J. Crescenz VA Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>July 3, 2019</last_update_submitted>
  <last_update_submitted_qc>July 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2019</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>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vedolizumab</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/NCT03237260
org study id: 825665
nct id: NCT03237260
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this research study is to determine whether starting the drug vedolizumab
      earlier than its FDA approved use can lead to better control of UC then using older drugs
      that we have historically used to treat UC. Vedolizumab is FDA-approved to be used after
      initial Corticosteroid treatments have failed or other UC treatments have failed. We will
      study if using vedolizumab as an early treatment for your UC will allow you to get off
      corticosteroids and prevent UC from worsening and requiring surgery.

      Vedolizumab is given intravenously initially every 2 weeks and then every 8 weeks.
Based upon our published data, 53% of patients who require CS at the time of diagnosis of UC
      will be in CS free remission in the absence of colectomy by the end of 52 weeks. Early
      corticosteroids requirement after the diagnosis of ulcerative colitis diagnosis can predict a
      more severe long-term course of the disease. This work formed the basis of this research
      project. We had postulated that patients requiring steroids early in the course of their
      disease had worse prognosis than those who did not and should be treated more aggressively
      early in the course of their disease to prevent future complications like colectomy.

      The current standard of care for treatment of UC in the VA is as follows:

      At the time of diagnosis all the patients are started on a 5-ASA compound. Those patients who
      have very severe disease are concomitantly started on steroids. If they are very sick they
      are concomitantly started on an anti-TNF compound also with the goal of tapering them off
      steroids. Based upon response to therapy medications are adjusted. If there is no relief with
      5-ASA compounds they can be started on steroids. For those on steroids and who cannot be
      weaned off steroids or are requiring multiple courses of steroids, they will have their
      therapy advanced to an anti-TNF or vedoluzimab. For those failing an anti-TNF they can be
      shifted to vedoluzimab. Thus, at the VA, vedoluzimab is available at the VA thru the
      non-formulary process. It is restricted to GI as 3rd line agent for UC. That is, it is used
      after oral agents fail and after anti-TNF agents (Humira® or Remicade®). The indications for
      Vedoluzimab use in the VA are as follows with regard to failure:

      The patient has had adequate therapeutic trials of ONE of the following treatments, unless
      the patient has a contraindication, risk factor for serious adverse event*, or intolerance to
      the agent(s):

      Criterion 1 is an option with or without therapeutic drug monitoring.)

      A TNFI and an antimetabolite immunomodulator, separately or in combination. OR An initial and
      second TNFI, if therapeutic drug monitoring after secondary nonresponse to TNFI therapy
      indicates high titers of anti-TNFI antibodies.

      OR

      A TNFI, when either of the following apply:

      Induction therapy with an agent from a different biologic class is needed to treat an
      inadequate response (with confirmed active inflammation / persistent disease) following TNFI
      induction therapy (i.e., primary nonresponse) and therapeutic drug monitoring shows
      therapeutic or high trough TNFI serum concentrations.

      The patient lost response (i.e., secondary nonresponse not due to adverse reaction) to the
      initial TNFI in association with therapeutic or high trough TNFI serum concentration.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: corticosteroid free remission as well as the absence of a colectomy
time frame: 52 weeks
description: corticosteroid free remission as well as the absence of a colectomy
arm group label: Vedolizumab 300mg
arm group type: Experimental
description: vedolizumab open label
intervention type: Drug
intervention name: Vedolizumab
description: Initiation: 300 mg at week 0, 2 and 6. Maintenance: Every 8 weeks after the sixth week at a fixed dose of 300 mg
arm group label: Vedolizumab 300mg
other name: entyvio
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Nabeel Khan, MD
role: Principal Investigator
affiliation: Assistant Professor of Clinical Medicine
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
mesh term: Vedolizumab
sharing ipd: No