<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/NCT03802214</url>
  </required_header>
  <id_info>
    <org_study_id>IRB48889</org_study_id>
    <nct_id>NCT03802214</nct_id>
  </id_info>
  <brief_title>Ulcerative Colitis - Vedolizumab- With/Without Prior Exposure to Anti-TNF（Tumor Necrosis Factor）Therapy</brief_title>
  <official_title>A Case-control Study to Evaluate the Immunoinflammatory Effect of Prior Exposure to Anti-TNF Therapy in Patients With Ulcerative Colitis Starting Vedolizumab Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Western Ontario, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</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>
      A case-control study to evaluate the immunoinflammatory effect of prior exposure to anti-TNF&#xD;
      therapy in patients with ulcerative colitis starting vedolizumab therapy&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Inflammatory bowel disease (IBD)- ulcerative colitis (UC) and Crohn's disease (CD)- are&#xD;
      chronic conditions of the gastrointestinal tract. Treatment generally consists of&#xD;
      immunosuppression to modify the dysregulated immune responses. Vedolizumab, an inhibitor of&#xD;
      α4β7, is a highly effective therapy for treating IBD, that minimized adverse effects through&#xD;
      its gut selective inhibition of lymphocyte trafficking. However, the mechanism of action&#xD;
      remains incompletely characterized especially in those previously treated to other biologics&#xD;
      and why some patients are either vedolizumab non-responders or fail to respond over time. We&#xD;
      would like to address the question whether anti-TNF non-responders as well as those that&#xD;
      either do not respond or fail overtime to respond to vedolizumab identifies a specific&#xD;
      population with difficult to treat disease that have alternate trafficking patterns and&#xD;
      whether prior exposure to anti-TNF alters the mucosal immune responses, and/or trafficking&#xD;
      patterns when compared to anti-TNF naive patients that may help explain impaired response to&#xD;
      vedolizumab induction therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Funding discontinued&#xD;
  </why_stopped>
  <start_date type="Actual">October 29, 2020</start_date>
  <completion_date type="Actual">December 11, 2020</completion_date>
  <primary_completion_date type="Actual">December 11, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells)</measure>
    <time_frame>changes from enrollment to end of treatment (week 14)</time_frame>
    <description>Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells) in patients with and without prior anti-TNF exposure</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Analysis of the serum and tissue concentrations of inflammatory markers (interleukins)</measure>
    <time_frame>changes from enrollment to end of treatment (week 14)</time_frame>
    <description>Analysis of the serum and tissue concentrations of inflammatory markers (interleukins) in vedolizumab responders versus non-responders</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of the serum and tissue concentrations of vedolizumab</measure>
    <time_frame>changes from enrollment to end of treatment (week 14)</time_frame>
    <description>Analysis of the serum and tissue concentrations of vedolizumab in patients with and without prior anti-TNF exposure</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">1</enrollment>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>vedolizumab-UC-naïve to TNF-antagonist</arm_group_label>
    <description>standard vedolizumab induction therapy for ulcerative colitis patients who are naïve to TNF-antagonist therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>vedolizumab-UC- previous TNF-antagonist</arm_group_label>
    <description>standard vedolizumab induction therapy for ulcerative colitis patients with previous TNF-antagonist exposure</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vedolizumab</intervention_name>
    <description>standard vedolizumab induction (300mg IV at week 0, 2, 6)</description>
    <arm_group_label>vedolizumab-UC- previous TNF-antagonist</arm_group_label>
    <arm_group_label>vedolizumab-UC-naïve to TNF-antagonist</arm_group_label>
    <other_name>Entyvio</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      collection of blood and tissue specimens for immunology and drug assessment&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        clinical indication for biologic therapy, adult patients (&gt;18) with the diagnosis of&#xD;
        inflammatory bowel disease (Ulcerative Colitis) who are naive or failed anti-TNF therapy&#xD;
        previously.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adult patients (&gt;18 years old)&#xD;
&#xD;
          -  clinical diagnosis of inflammatory bowel disease (Ulcerative Colitis)&#xD;
&#xD;
          -  clinical indication for biologic therapy&#xD;
&#xD;
          -  naive or failed anti-TNF therapy previously&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients allergic or intolerant to vedolizumab,&#xD;
&#xD;
          -  past use of vedolizumab;&#xD;
&#xD;
          -  patient unable to give consent to enter the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aida Habtezion, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Western Ontario</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Schmitt H, Billmeier U, Dieterich W, Rath T, Sonnewald S, Reid S, Hirschmann S, Hildner K, Waldner MJ, Mudter J, Hartmann A, Grutzmann R, Neufert C, Munster T, Neurath MF, Atreya R. Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn's disease. Gut. 2019 May;68(5):814-828. doi: 10.1136/gutjnl-2017-315671. Epub 2018 May 30.</citation>
    <PMID>29848778</PMID>
  </reference>
  <reference>
    <citation>Boden EK, Shows DM, Chiorean MV, Lord JD. Identification of Candidate Biomarkers Associated with Response to Vedolizumab in Inflammatory Bowel Disease. Dig Dis Sci. 2018 Sep;63(9):2419-2429. doi: 10.1007/s10620-018-4924-8. Epub 2018 Jan 25.</citation>
    <PMID>29372476</PMID>
  </reference>
  <reference>
    <citation>Suzawa K, Kobayashi M, Sakai Y, Hoshino H, Watanabe M, Harada O, Ohtani H, Fukuda M, Nakayama J. Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis. Am J Gastroenterol. 2007 Jul;102(7):1499-509. doi: 10.1111/j.1572-0241.2007.01189.x. Epub 2007 Apr 24.</citation>
    <PMID>17459027</PMID>
  </reference>
  <reference>
    <citation>Kobayashi M, Hoshino H, Masumoto J, Fukushima M, Suzawa K, Kageyama S, Suzuki M, Ohtani H, Fukuda M, Nakayama J. GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitis. Inflamm Bowel Dis. 2009 May;15(5):697-706. doi: 10.1002/ibd.20827.</citation>
    <PMID>19067429</PMID>
  </reference>
  <reference>
    <citation>Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A; GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013 Aug 22;369(8):711-21. doi: 10.1056/NEJMoa1215739.</citation>
    <PMID>23964933</PMID>
  </reference>
  <reference>
    <citation>Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.</citation>
    <PMID>23964932</PMID>
  </reference>
  <reference>
    <citation>Rosario M, Dirks NL, Gastonguay MR, Fasanmade AA, Wyant T, Parikh A, Sandborn WJ, Feagan BG, Reinisch W, Fox I. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease. Aliment Pharmacol Ther. 2015 Jul;42(2):188-202. doi: 10.1111/apt.13243. Epub 2015 May 20. Erratum In: Aliment Pharmacol Ther. 2015 Nov;42(9):1135.</citation>
    <PMID>25996351</PMID>
  </reference>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>December 17, 2020</last_update_submitted>
  <last_update_submitted_qc>December 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Aida Habtezion</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </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>
    <ipd_description>We will share the data through the publication of results. Individual participant data was not promised to be shared.</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/NCT03802214
org study id: IRB48889
nct id: NCT03802214
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
A case-control study to evaluate the immunoinflammatory effect of prior exposure to anti-TNF
      therapy in patients with ulcerative colitis starting vedolizumab therapy
Inflammatory bowel disease (IBD)- ulcerative colitis (UC) and Crohn's disease (CD)- are
      chronic conditions of the gastrointestinal tract. Treatment generally consists of
      immunosuppression to modify the dysregulated immune responses. Vedolizumab, an inhibitor of
      α4β7, is a highly effective therapy for treating IBD, that minimized adverse effects through
      its gut selective inhibition of lymphocyte trafficking. However, the mechanism of action
      remains incompletely characterized especially in those previously treated to other biologics
      and why some patients are either vedolizumab non-responders or fail to respond over time. We
      would like to address the question whether anti-TNF non-responders as well as those that
      either do not respond or fail overtime to respond to vedolizumab identifies a specific
      population with difficult to treat disease that have alternate trafficking patterns and
      whether prior exposure to anti-TNF alters the mucosal immune responses, and/or trafficking
      patterns when compared to anti-TNF naive patients that may help explain impaired response to
      vedolizumab induction therapy.
observational model: Case-Control
time perspective: Prospective
measure: Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells)
time frame: changes from enrollment to end of treatment (week 14)
description: Analysis of blood and tissue leukocytes (T cells, B cells and Dendritic cells) in patients with and without prior anti-TNF exposure
measure: Analysis of the serum and tissue concentrations of inflammatory markers (interleukins)
time frame: changes from enrollment to end of treatment (week 14)
description: Analysis of the serum and tissue concentrations of inflammatory markers (interleukins) in vedolizumab responders versus non-responders
measure: Analysis of the serum and tissue concentrations of vedolizumab
time frame: changes from enrollment to end of treatment (week 14)
description: Analysis of the serum and tissue concentrations of vedolizumab in patients with and without prior anti-TNF exposure
arm group label: vedolizumab-UC-naïve to TNF-antagonist
description: standard vedolizumab induction therapy for ulcerative colitis patients who are naïve to TNF-antagonist therapy
arm group label: vedolizumab-UC- previous TNF-antagonist
description: standard vedolizumab induction therapy for ulcerative colitis patients with previous TNF-antagonist exposure
intervention type: Drug
intervention name: Vedolizumab
description: standard vedolizumab induction (300mg IV at week 0, 2, 6)
arm group label: vedolizumab-UC- previous TNF-antagonist
arm group label: vedolizumab-UC-naïve to TNF-antagonist
other name: Entyvio
collection of blood and tissue specimens for immunology and drug assessment
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Aida Habtezion, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
facility: 
country: Canada
country: United States
citation: Schmitt H, Billmeier U, Dieterich W, Rath T, Sonnewald S, Reid S, Hirschmann S, Hildner K, Waldner MJ, Mudter J, Hartmann A, Grutzmann R, Neufert C, Munster T, Neurath MF, Atreya R. Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn's disease. Gut. 2019 May;68(5):814-828. doi: 10.1136/gutjnl-2017-315671. Epub 2018 May 30.
PMID: 29848778
citation: Boden EK, Shows DM, Chiorean MV, Lord JD. Identification of Candidate Biomarkers Associated with Response to Vedolizumab in Inflammatory Bowel Disease. Dig Dis Sci. 2018 Sep;63(9):2419-2429. doi: 10.1007/s10620-018-4924-8. Epub 2018 Jan 25.
PMID: 29372476
citation: Suzawa K, Kobayashi M, Sakai Y, Hoshino H, Watanabe M, Harada O, Ohtani H, Fukuda M, Nakayama J. Preferential induction of peripheral lymph node addressin on high endothelial venule-like vessels in the active phase of ulcerative colitis. Am J Gastroenterol. 2007 Jul;102(7):1499-509. doi: 10.1111/j.1572-0241.2007.01189.x. Epub 2007 Apr 24.
PMID: 17459027
citation: Kobayashi M, Hoshino H, Masumoto J, Fukushima M, Suzawa K, Kageyama S, Suzuki M, Ohtani H, Fukuda M, Nakayama J. GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitis. Inflamm Bowel Dis. 2009 May;15(5):697-706. doi: 10.1002/ibd.20827.
PMID: 19067429
citation: Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A; GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013 Aug 22;369(8):711-21. doi: 10.1056/NEJMoa1215739.
PMID: 23964933
citation: Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013 Aug 22;369(8):699-710. doi: 10.1056/NEJMoa1215734.
PMID: 23964932
citation: Rosario M, Dirks NL, Gastonguay MR, Fasanmade AA, Wyant T, Parikh A, Sandborn WJ, Feagan BG, Reinisch W, Fox I. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease. Aliment Pharmacol Ther. 2015 Jul;42(2):188-202. doi: 10.1111/apt.13243. Epub 2015 May 20. Erratum In: Aliment Pharmacol Ther. 2015 Nov;42(9):1135.
PMID: 25996351
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Aida Habtezion
investigator title: Associate Professor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
mesh term: Vedolizumab
sharing ipd: No
ipd description: We will share the data through the publication of results. Individual participant data was not promised to be shared.