<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/NCT03772145</url>
  </required_header>
  <id_info>
    <org_study_id>18-2435</org_study_id>
    <nct_id>NCT03772145</nct_id>
  </id_info>
  <brief_title>Tofacitinib Response in Ulcerative Colitis - a Real World Prospective Multi-center Study</brief_title>
  <acronym>TOUR</acronym>
  <official_title>TOUR: Tofacitinib Response in Ulcerative Colitis - a Real World Prospective Multi-center Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overarching goal of this study, is to create a longitudinally followed, well phenotyped&#xD;
      cohort of patients with UC starting treatment with tofacitinib in the setting of standard of&#xD;
      care who have linked clinical data and self-reported outcome data that will lead to&#xD;
      evaluation of efficacy and safety of tofacitinib in the real-life setting. The specific aims&#xD;
      for the study are:&#xD;
&#xD;
        1. Create a prospective cohort of well phenotyped (proctitis vs. rectosigmoiditis vs.&#xD;
           extensive) adult UC patients with serial clinical and patient-reported data collected&#xD;
           throughout the course of 12 months of tofacitinib therapy. Enrolled patients on therapy&#xD;
           will be followed up to 36 months after the start of therapy.&#xD;
&#xD;
        2. To determine clinical response rates and persistence of therapy with tofacitinib for&#xD;
           induction and maintenance therapy&#xD;
&#xD;
        3. Describe the incidence of specific drug-associated adverse events (shingles, serious&#xD;
           infections), hospitalizations and surgeries in the standard of care setting.&#xD;
&#xD;
        4. Assess the correlation of various outcome measures in ulcerative colitis (Simple&#xD;
           Clinical Colitis Activity Index (SCCAI), partial Mayo index, 6-point index) and&#xD;
           endoscopic outcomes via the endoscopic Mayo Score&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The proposed prospective tofacitinib registry is a prospective patient cohort with the goal&#xD;
      of evaluating the efficacy and safety of this drug in &quot;real life&quot;. All patients starting&#xD;
      tofacitinib for ulcerative colitis in the setting of standard of care therapy will be&#xD;
      eligible within of 4 weeks of start of therapy. Preferentially, patients will be enrolled at&#xD;
      the visit where therapy is initiated. At baseline patient characteristics including extent of&#xD;
      disease, previous therapies (including number of previously failed biologics) and&#xD;
      pro-inflammatory laboratory markers (CRP, if available calprotectin) will be captured in a&#xD;
      prospective web-based database. Additionally, each consented study participant will be&#xD;
      enrolled in a web-based prospective patient powered registry (PPR) to evaluate patient report&#xD;
      outcomes (PRO's) (such as validated measures for depression, social satisfaction, pain,&#xD;
      fatigue) and safety events (e.g. hospitalizations; herpes zoster, complications requiring&#xD;
      discontinuation of tofacitinib).&#xD;
&#xD;
      The following outcomes will be assessed: Response and remission as assessed by the Simple&#xD;
      Clinical Colitis Activity Index (SCCAI) (primary endpoint), in addition secondary outcomes&#xD;
      will include: the partial Mayo score, the 6-point subscore of the Mayo score, and the&#xD;
      Manitoba index, need for steroids, need for surgery or hospitalization, need for dosing&#xD;
      intensification or reduction of dosing as well as persistence of tofacitinib therapy.&#xD;
      Endoscopy information will be collected if done as part of routine care, but the study will&#xD;
      not have an endoscopic requirement. Sites will be encouraged to report a Mayo endoscopic&#xD;
      score if done as part of routine care as a secondary endpoint. The outcomes will be&#xD;
      determined in the setting of the standard of care visits, which normally are scheduled at the&#xD;
      end of induction (approx. 6-12 weeks after the start of tofacitinib) and during maintenance&#xD;
      therapy after 4-6 and 9-12 months and then every 3-4 months up to 36 months. PRO's and safety&#xD;
      will be assessed with the PPR instrument at baseline, daily in the first 2 weeks to better&#xD;
      understand rapidity of onset, and after 6,10,14,22,30,38,46 and 54 weeks and then every 3-4&#xD;
      months up to 36 months. The analyses of these data will facilitate UC patient care and&#xD;
      improve the overall quality of IBD therapy in the US and worldwide. This study is to be&#xD;
      conducted according to US and international standards of Good Clinical Practice (FDA Title 21&#xD;
      part 312 and International Conference on Harmonization guidelines), applicable government&#xD;
      regulations and Institutional research policies and procedures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">November 27, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>36 Months</target_duration>
  <primary_outcome>
    <measure>Change in clinical response from baseline</measure>
    <time_frame>At baseline and at approximately 2, 6, 10, 22 and 54, 78, 91, 104, 117, 130, 143 and 156 weeks after start of tofacitinib</time_frame>
    <description>Clinical response as assessed by the Simple Clinical Colitis Activity Index (SCCAI)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in clinical remission from baseline</measure>
    <time_frame>At baseline and at approximately 2, 6, 10, 22 and 54, 78, 91, 104, 117, 130, 143 and 156 weeks after start of tofacitinib</time_frame>
    <description>Clinical remission as assessed by the Simple Clinical Colitis Activity Index (SCCAI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persistence of the initial tofacitinib dose</measure>
    <time_frame>36 months</time_frame>
    <description>Persistence of initial tofacitinib dose</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>Tofacitinib</arm_group_label>
    <description>Adult patients, age 18 years or older, with UC, who within 2 weeks have been started on tofacitinib therapy for moderate to severe UC or who plan to start this therapy within the next 2 weeks. The start of the tofacitinib therapy must have been or be initiated in the setting of standard of care therapy</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients, age 18 years or older, with UC, who within 2 weeks have been started on&#xD;
        tofacitinib therapy for moderate to severe UC or who plan to start this therapy within the&#xD;
        next 2 weeks. The start of the tofacitinib therapy must have been or be initiated in the&#xD;
        setting of standard of care therapy&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult patients, age 18 years or older, with UC, who within 2 weeks have been started&#xD;
             on tofacitinib therapy for moderate to severe UC or who plan to start this therapy&#xD;
             within the next 2 weeks. The start of the tofacitinib therapy must have been or be&#xD;
             initiated in the setting of standard of care therapy&#xD;
&#xD;
          2. Anticipation that the patient will be followed by the participating center at least&#xD;
             for the next 12 months&#xD;
&#xD;
          3. Diagnosis of UC must be established on the basis of standard clinical, radiographic,&#xD;
             endoscopic, and histologic criteria as described below.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Patients will be excluded if they meet any of the following criteria:&#xD;
&#xD;
               1. Inability to provide informed consent&#xD;
&#xD;
               2. Patients presenting for a one-time consultation&#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>Hans Herfarth, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Millie Long</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Division of Gastroenterology and Hepatology</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>April 18, 2023</last_update_submitted>
  <last_update_submitted_qc>April 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ulcerative colitis</keyword>
  <keyword>Inflammatory bowel diseases</keyword>
  <keyword>Tofacitinib</keyword>
  <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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>There is currently no plan to share the anonymized data with other investigators. But this may change in the future</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/NCT03772145
org study id: 18-2435
nct id: NCT03772145
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The overarching goal of this study, is to create a longitudinally followed, well phenotyped
      cohort of patients with UC starting treatment with tofacitinib in the setting of standard of
      care who have linked clinical data and self-reported outcome data that will lead to
      evaluation of efficacy and safety of tofacitinib in the real-life setting. The specific aims
      for the study are:

        1. Create a prospective cohort of well phenotyped (proctitis vs. rectosigmoiditis vs.
           extensive) adult UC patients with serial clinical and patient-reported data collected
           throughout the course of 12 months of tofacitinib therapy. Enrolled patients on therapy
           will be followed up to 36 months after the start of therapy.

        2. To determine clinical response rates and persistence of therapy with tofacitinib for
           induction and maintenance therapy

        3. Describe the incidence of specific drug-associated adverse events (shingles, serious
           infections), hospitalizations and surgeries in the standard of care setting.

        4. Assess the correlation of various outcome measures in ulcerative colitis (Simple
           Clinical Colitis Activity Index (SCCAI), partial Mayo index, 6-point index) and
           endoscopic outcomes via the endoscopic Mayo Score
The proposed prospective tofacitinib registry is a prospective patient cohort with the goal
      of evaluating the efficacy and safety of this drug in "real life". All patients starting
      tofacitinib for ulcerative colitis in the setting of standard of care therapy will be
      eligible within of 4 weeks of start of therapy. Preferentially, patients will be enrolled at
      the visit where therapy is initiated. At baseline patient characteristics including extent of
      disease, previous therapies (including number of previously failed biologics) and
      pro-inflammatory laboratory markers (CRP, if available calprotectin) will be captured in a
      prospective web-based database. Additionally, each consented study participant will be
      enrolled in a web-based prospective patient powered registry (PPR) to evaluate patient report
      outcomes (PRO's) (such as validated measures for depression, social satisfaction, pain,
      fatigue) and safety events (e.g. hospitalizations; herpes zoster, complications requiring
      discontinuation of tofacitinib).

      The following outcomes will be assessed: Response and remission as assessed by the Simple
      Clinical Colitis Activity Index (SCCAI) (primary endpoint), in addition secondary outcomes
      will include: the partial Mayo score, the 6-point subscore of the Mayo score, and the
      Manitoba index, need for steroids, need for surgery or hospitalization, need for dosing
      intensification or reduction of dosing as well as persistence of tofacitinib therapy.
      Endoscopy information will be collected if done as part of routine care, but the study will
      not have an endoscopic requirement. Sites will be encouraged to report a Mayo endoscopic
      score if done as part of routine care as a secondary endpoint. The outcomes will be
      determined in the setting of the standard of care visits, which normally are scheduled at the
      end of induction (approx. 6-12 weeks after the start of tofacitinib) and during maintenance
      therapy after 4-6 and 9-12 months and then every 3-4 months up to 36 months. PRO's and safety
      will be assessed with the PPR instrument at baseline, daily in the first 2 weeks to better
      understand rapidity of onset, and after 6,10,14,22,30,38,46 and 54 weeks and then every 3-4
      months up to 36 months. The analyses of these data will facilitate UC patient care and
      improve the overall quality of IBD therapy in the US and worldwide. This study is to be
      conducted according to US and international standards of Good Clinical Practice (FDA Title 21
      part 312 and International Conference on Harmonization guidelines), applicable government
      regulations and Institutional research policies and procedures.
observational model: Cohort
time perspective: Prospective
measure: Change in clinical response from baseline
time frame: At baseline and at approximately 2, 6, 10, 22 and 54, 78, 91, 104, 117, 130, 143 and 156 weeks after start of tofacitinib
description: Clinical response as assessed by the Simple Clinical Colitis Activity Index (SCCAI)
measure: Change in clinical remission from baseline
time frame: At baseline and at approximately 2, 6, 10, 22 and 54, 78, 91, 104, 117, 130, 143 and 156 weeks after start of tofacitinib
description: Clinical remission as assessed by the Simple Clinical Colitis Activity Index (SCCAI)
measure: Persistence of the initial tofacitinib dose
time frame: 36 months
description: Persistence of initial tofacitinib dose
arm group label: Tofacitinib
description: Adult patients, age 18 years or older, with UC, who within 2 weeks have been started on tofacitinib therapy for moderate to severe UC or who plan to start this therapy within the next 2 weeks. The start of the tofacitinib therapy must have been or be initiated in the setting of standard of care therapy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Hans Herfarth, MD
role: Principal Investigator
affiliation: University of North Carolina
last name: Millie Long
role: Principal Investigator
affiliation: University of North Carolina
facility: 
country: United States
responsible party type: Sponsor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
sharing ipd: Undecided
ipd description: There is currently no plan to share the anonymized data with other investigators. But this may change in the future