<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/NCT03798691</url>
  </required_header>
  <id_info>
    <org_study_id>2018-1037</org_study_id>
    <secondary_id>SMPH/MEDICINE/GASTROENT</secondary_id>
    <secondary_id>A534250</secondary_id>
    <secondary_id>Protocol Version 9/22/2021</secondary_id>
    <nct_id>NCT03798691</nct_id>
  </id_info>
  <brief_title>Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab</brief_title>
  <official_title>A Pilot Study Evaluating Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boston Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Wisconsin, Madison</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Inflammatory bowel disease (IBD) is a chronic inflammatory state of the gastrointestinal&#xD;
      tract(1) affecting 1.6-3.1 million people in the United States. Patients with IBD are treated&#xD;
      with immunosuppressants that increase their risk of herpes zoster (HZ), also known as&#xD;
      shingles.&#xD;
&#xD;
      Those with IBD have a two-fold increased risk for HZ compared to age matched controls.&#xD;
      Because most IBD patients are treated with systemic immunosuppressants, which are an&#xD;
      independent risk factor for HZ, the live attenuated HZ vaccine was not recommended. However,&#xD;
      the release of the new inactivated HZ vaccine, Shingrix (GlaxoSmithKline), presents new&#xD;
      opportunities for preventive care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to determine the immunogenicity of the herpes zoster subunit&#xD;
      vaccine in inflammatory bowel disease patients on vedolizumab compared to those on anti-tumor&#xD;
      necrosis factor (TNF) monotherapy.&#xD;
&#xD;
      The study will evaluate humoral and cell mediated immunity in patients with IBD on&#xD;
      vedolizumab who receive the two-dose herpes zoster vaccine. The investigators will evaluate&#xD;
      short term, one month after second vaccination dose and sustained immunogenicity at 6 and 12&#xD;
      months post vaccination.&#xD;
&#xD;
      The central hypothesis of this proposal is that IBD patients on vedolizumab should be able to&#xD;
      mount a normal vaccine response comparable to those on anti-TNF monotherapy who might benefit&#xD;
      from a third dose of the subunit vaccine as has been evaluated in HIV and transplant&#xD;
      populations. The hypothesis is that IBD patients on vedolizumab will be able to mount a&#xD;
      superior response to those on anti-TNF therapy. A recent study showed that hepatitis B&#xD;
      vaccine immunogenicity was not affected by vedolizumab.&#xD;
&#xD;
      The study population will include adult patients aged 50 or older with IBD(diagnosed by&#xD;
      standard clinical, radiographic, endoscopic, and histopathologic criteria) receiving care at&#xD;
      University of Wisconsin Hospital and Clinics or Boston Medical Center. There is no&#xD;
      randomization or use of placebo in this study. Two study groups (each containing 15 subjects)&#xD;
      will be established Group A: Patients with IBD on anti-TNF monotherapy and Group B patients&#xD;
      with IBD on vedolizumab monotherapy.&#xD;
&#xD;
      Methods: Eligible patients with IBD will be recruited from the University of Wisconsin&#xD;
      Hospital and Clinics or from Center for Digestive Diseases at Boston Medical Center.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 28, 2019</start_date>
  <completion_date type="Anticipated">February 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in cell mediated immunity</measure>
    <time_frame>It will be measured from pre-immunization to 1 month after receiving second dose of booster vaccine post-immunization.</time_frame>
    <description>The primary objective will be the change in cell mediated immunity (CMI) as measured by ELISPOT from pre-immunization to one month after receiving second dose of vaccine.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of participants with sustained cell mediated immunity measured via ELISPOT after immunization.</measure>
    <time_frame>Baseline to 6 months post-immunization 2nd dose of vaccine.</time_frame>
    <description>Sustained change in CMI at 6 months will be assessed after receiving a second dose of booster vaccine post-immunization. CMI will be measured via ELISPOT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of participants with a change in antibody concentration post immunization</measure>
    <time_frame>pre-immunization to one month 2nd dose post-immunization</time_frame>
    <description>A secondary outcome will be the change in varicella zoster virus (VZV) antibody concentration comparing pre-immunization to post immunization antibody concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of participants with a change in antibody concentration that is sustained at 6 months</measure>
    <time_frame>Baseline to 6 months post-immunization</time_frame>
    <description>Sustained change in VZV antibody concentration at 6 months after receiving a second dose of booster vaccine post-immunization will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Vaccine related adverse effects</measure>
    <time_frame>This will be done at months 1, 2 and 3.</time_frame>
    <description>To evaluate for adverse effects following immunization patients will receive phone calls from study personnel to ascertain vaccine-related adverse effects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of change in disease activity post immunization</measure>
    <time_frame>at the baseline visit and one month after receipt of each vaccine</time_frame>
    <description>The Simple Clinical Colitis Activity Index (SCCAI) will be used to measure disease activity. It is a questionnaire with six subscore topics with scores defined by UC signs and symptoms from 0 to 4 for a range of scores from 0 to 17. Total scores are interpreted as: Remission = score of 0 to 4 points, Mild Activity = score of 5 to 7 points, Moderate Activity = Score of 8 to 16 points, and Severe Activity = Score of &gt; 16 points.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Inflammatory Bowel Diseases</condition>
  <condition>Crohn Disease</condition>
  <condition>Ulcerative Colitis</condition>
  <condition>Herpes Zoster</condition>
  <arm_group>
    <arm_group_label>Anti-TNF monotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with IBD on Anti-TNF monotherapy will be given the shingrix vaccine. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vedolizumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with IBD on vedolizumab monotherapy will be given the shingrix vaccine.&#xD;
Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Shingrix</intervention_name>
    <description>Biological: SHINGRIX&#xD;
SHINGRIX is a vaccine indicated for prevention of herpes zoster (shingles) in adults aged 18 years and older.&#xD;
SHINGRIX is a suspension for injection supplied as a single-dose vial of lyophilized glycoprotein e (ge) antigen component to be reconstituted with the accompanying vial of AS01B adjuvant suspension component. A single dose after reconstitution is 0.5 mL.&#xD;
Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.</description>
    <arm_group_label>Anti-TNF monotherapy</arm_group_label>
    <arm_group_label>Vedolizumab</arm_group_label>
    <other_name>Recombinant zoster vaccine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient is between the ages of 18-70 years, inclusive.&#xD;
&#xD;
          2. History of primary varicella infection (chicken pox) Confirmed by a previous history&#xD;
             of positive varicella zoster virus (VZV) Immunoglobulin G antibody or history of&#xD;
             chicken pox&#xD;
&#xD;
          3. Patient has a history of ulcerative colitis (UC) or Crohn's disease diagnosed by&#xD;
             standard clinical, radiographic, endoscopic, and histopathologic criteria.&#xD;
&#xD;
          4. Patient is receiving one of the following treatments for their IBD Group A: Anti-TNF&#xD;
             monotherapy (adalimumab, certolizumab, golimumab, infliximab) Group B: Vedolizumab&#xD;
             monotherapy&#xD;
&#xD;
          5. Patient has been on stable treatment for IBD for at least three months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous receipt of any HZ vaccine&#xD;
&#xD;
          2. Allergy to zoster vaccine or a component of it&#xD;
&#xD;
          3. Other underlying chronic medical condition that could affect immunogenicity to&#xD;
             vaccines (rheumatoid arthritis, etc.)&#xD;
&#xD;
          4. History of herpes zoster or post herpetic neuralgia within the past year.&#xD;
&#xD;
          5. Patient cannot or will not provide written informed consent.&#xD;
&#xD;
          6. Patient is being administered immunomodulators currently or within the past three&#xD;
             months&#xD;
&#xD;
          7. Patient has been taking any dose of oral or intravenous steroids within 30 days prior&#xD;
             to immunization.&#xD;
&#xD;
          8. Patient has received polyclonal immunoglobulin therapy or blood products within the&#xD;
             last year.&#xD;
&#xD;
          9. Patient is pregnant per self-reporting or older than age 70 years&#xD;
&#xD;
         10. Unable to provide appropriate informed consent due to being illiterate or impairment&#xD;
             in decision-making capacity.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Wisconsin Digestive Health Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 10, 2019</study_first_posted>
  <last_update_submitted>July 10, 2023</last_update_submitted>
  <last_update_submitted_qc>July 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2023</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>Herpes Simplex</mesh_term>
    <mesh_term>Herpes Zoster</mesh_term>
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</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/NCT03798691
org study id: 2018-1037
secondary id: SMPH/MEDICINE/GASTROENT
secondary id: A534250
secondary id: Protocol Version 9/22/2021
nct id: NCT03798691
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Inflammatory bowel disease (IBD) is a chronic inflammatory state of the gastrointestinal
      tract(1) affecting 1.6-3.1 million people in the United States. Patients with IBD are treated
      with immunosuppressants that increase their risk of herpes zoster (HZ), also known as
      shingles.

      Those with IBD have a two-fold increased risk for HZ compared to age matched controls.
      Because most IBD patients are treated with systemic immunosuppressants, which are an
      independent risk factor for HZ, the live attenuated HZ vaccine was not recommended. However,
      the release of the new inactivated HZ vaccine, Shingrix (GlaxoSmithKline), presents new
      opportunities for preventive care.
The purpose of this study is to determine the immunogenicity of the herpes zoster subunit
      vaccine in inflammatory bowel disease patients on vedolizumab compared to those on anti-tumor
      necrosis factor (TNF) monotherapy.

      The study will evaluate humoral and cell mediated immunity in patients with IBD on
      vedolizumab who receive the two-dose herpes zoster vaccine. The investigators will evaluate
      short term, one month after second vaccination dose and sustained immunogenicity at 6 and 12
      months post vaccination.

      The central hypothesis of this proposal is that IBD patients on vedolizumab should be able to
      mount a normal vaccine response comparable to those on anti-TNF monotherapy who might benefit
      from a third dose of the subunit vaccine as has been evaluated in HIV and transplant
      populations. The hypothesis is that IBD patients on vedolizumab will be able to mount a
      superior response to those on anti-TNF therapy. A recent study showed that hepatitis B
      vaccine immunogenicity was not affected by vedolizumab.

      The study population will include adult patients aged 50 or older with IBD(diagnosed by
      standard clinical, radiographic, endoscopic, and histopathologic criteria) receiving care at
      University of Wisconsin Hospital and Clinics or Boston Medical Center. There is no
      randomization or use of placebo in this study. Two study groups (each containing 15 subjects)
      will be established Group A: Patients with IBD on anti-TNF monotherapy and Group B patients
      with IBD on vedolizumab monotherapy.

      Methods: Eligible patients with IBD will be recruited from the University of Wisconsin
      Hospital and Clinics or from Center for Digestive Diseases at Boston Medical Center.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in cell mediated immunity
time frame: It will be measured from pre-immunization to 1 month after receiving second dose of booster vaccine post-immunization.
description: The primary objective will be the change in cell mediated immunity (CMI) as measured by ELISPOT from pre-immunization to one month after receiving second dose of vaccine.
measure: Percent of participants with sustained cell mediated immunity measured via ELISPOT after immunization.
time frame: Baseline to 6 months post-immunization 2nd dose of vaccine.
description: Sustained change in CMI at 6 months will be assessed after receiving a second dose of booster vaccine post-immunization. CMI will be measured via ELISPOT
measure: Percent of participants with a change in antibody concentration post immunization
time frame: pre-immunization to one month 2nd dose post-immunization
description: A secondary outcome will be the change in varicella zoster virus (VZV) antibody concentration comparing pre-immunization to post immunization antibody concentration.
measure: Percent of participants with a change in antibody concentration that is sustained at 6 months
time frame: Baseline to 6 months post-immunization
description: Sustained change in VZV antibody concentration at 6 months after receiving a second dose of booster vaccine post-immunization will be assessed.
measure: Incidence of Vaccine related adverse effects
time frame: This will be done at months 1, 2 and 3.
description: To evaluate for adverse effects following immunization patients will receive phone calls from study personnel to ascertain vaccine-related adverse effects.
measure: Incidence of change in disease activity post immunization
time frame: at the baseline visit and one month after receipt of each vaccine
description: The Simple Clinical Colitis Activity Index (SCCAI) will be used to measure disease activity. It is a questionnaire with six subscore topics with scores defined by UC signs and symptoms from 0 to 4 for a range of scores from 0 to 17. Total scores are interpreted as: Remission = score of 0 to 4 points, Mild Activity = score of 5 to 7 points, Moderate Activity = Score of 8 to 16 points, and Severe Activity = Score of > 16 points.
arm group label: Anti-TNF monotherapy
arm group type: Active Comparator
description: Patients with IBD on Anti-TNF monotherapy will be given the shingrix vaccine. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.
arm group label: Vedolizumab
arm group type: Active Comparator
description: Patients with IBD on vedolizumab monotherapy will be given the shingrix vaccine.
Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.
intervention type: Biological
intervention name: Shingrix
description: Biological: SHINGRIX
SHINGRIX is a vaccine indicated for prevention of herpes zoster (shingles) in adults aged 18 years and older.
SHINGRIX is a suspension for injection supplied as a single-dose vial of lyophilized glycoprotein e (ge) antigen component to be reconstituted with the accompanying vial of AS01B adjuvant suspension component. A single dose after reconstitution is 0.5 mL.
Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.
arm group label: Anti-TNF monotherapy
arm group label: Vedolizumab
other name: Recombinant zoster vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Herpes Simplex
mesh term: Herpes Zoster
mesh term: Crohn Disease
mesh term: Intestinal Diseases
mesh term: Inflammatory Bowel Diseases
mesh term: Vaccines
sharing ipd: No