xml: <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/NCT06027229</url>
    </required_header>
    <id_info>
      <org_study_id>2023-1208</org_study_id>
      <secondary_id>Protocol Version 8/23/2023</secondary_id>
      <secondary_id>SMPH/MEDICINE/GASTROENT</secondary_id>
      <nct_id>NCT06027229</nct_id>
    </id_info>
    <brief_title>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</brief_title>
    <official_title>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Wisconsin, Madison</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Novavax</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Wisconsin, Madison</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        To determine whether providing a recombinant booster COVID-19 vaccine improves sustained&#xD;
        humoral and cell-mediated immunogenicity against SARS-CoV-2 in immunosuppressed patients with&#xD;
        Inflammatory Bowel Disease (IBD) and/or solid organ transplant recipients. 120 participants&#xD;
        will be enrolled and can expect to be on study for 6 months.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This will be a single-center, prospective, unblinded, non-randomized study of 120&#xD;
        immunosuppressed patients who are planning to receive a recombinant COVID-19 vaccine booster&#xD;
        dose as standard of care and are willing to participate in the study. At least 35 patients&#xD;
        will have inflammatory bowel disease and at least 35 patients will be a solid organ&#xD;
        transplant recipient. After obtaining informed consent, individuals who meet the inclusion&#xD;
        criteria and none of the exclusion criteria will be invited to participate in the study.&#xD;
        Blood samples will be collected from each participant at the baseline visit (V1), at 1 month&#xD;
        post-booster (V2 visit), and 6 months post-booster (V3).&#xD;
  &#xD;
        Aim 1: To determine whether providing a recombinant booster COVID-19 vaccine improves&#xD;
        sustained humoral and cell-mediated immunogenicity against SARS-CoV-2 in immunosuppressed&#xD;
        patients with IBD and/or solid organ transplant recipients.&#xD;
  &#xD;
        The investigators hypothesize that solid organ transplant recipients receiving a combination&#xD;
        of immunosuppressive regimens will have lower antibody concentrations than patients with IBD&#xD;
        because previous work has shown that patients with IBD have higher rates of seroconversion&#xD;
        than solid organ transplant recipients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2024</completion_date>
    <primary_completion_date type="Anticipated">September 2024</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in Antibody Concentration from Baseline (visit 1) at 1 month (visit 2)</measure>
      <time_frame>baseline and 1 month</time_frame>
      <description>Antibody concentrations 1 month after the recombinant vaccine booster (V2) in patients with IBD and solid organ transplant recipients compared to their baseline visit (V1).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Seropositivity Rates</measure>
      <time_frame>1 month, 6 months</time_frame>
      <description>Seropositive will be defined by positive anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 performed by Labcorp.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percent of Participants Seronegative at Baseline and Subsequently Seropositive</measure>
      <time_frame>baseline, 1 month, 6 months</time_frame>
      <description>Percentages (and 2-sided 95% Confidence Intervals) of participants who were seronegative at baseline and became seropositive after immunization will be evaluated in each group. For initially seropositive subjects at V1, antibody concentration at post-vaccination (V2) ≥ 4 fold the pre-vaccination antibody concentration.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Interferon gamma responses at 1 month compared to baseline</measure>
      <time_frame>baseline and 1 month</time_frame>
      <description>An interferon gamma response will be considered any measurable response</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Interferon gamma responses at 6 months compared to 1 month</measure>
      <time_frame>1 month, 6 months</time_frame>
      <description>An interferon gamma response will be considered any measurable response</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Solicited Adverse Events (AEs)</measure>
      <time_frame>up to 7 days on study</time_frame>
      <description>The number of participants reporting each solicited local AE and each solicited systemic AE within seven days (Days 1-7) after the booster dose and overall will be summarized for both study groups.&#xD;
  Solicited local AEs included injection site pain, redness, and swelling.&#xD;
  Solicited systemic AEs included fatigue, myalgia, arthralgia, headache, shivering/chills, fever, and gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Unsolicited Adverse Events</measure>
      <time_frame>up to 30 days on study</time_frame>
      <description>The number of participants reporting unsolicited AEs within 30 days (Days 1-30) after the booster dose and overall will be summarized for both the study groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Potential Immune-Mediated Diseases (pIMDs)</measure>
      <time_frame>up to 6 months</time_frame>
      <description>The number of participants reporting pIMDs from the booster dose to the study end will be summarized for both study groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serious Adverse Events (SAEs)</measure>
      <time_frame>up to 6 months</time_frame>
      <description>The number of participants reporting SAEs and fatal SAEs from the booster dose administration to the study end will be summarized for both the study groups.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants reporting disease flares of IBD</measure>
      <time_frame>up to 6 months</time_frame>
      <description>Disease activity will be assessed by monitoring disease activity using the Short Crohn's Activity Index (SCAI)18 for patients with Crohn's disease or the Simple Clinical Colitis Activity Index (SCCAI) questionnaire for patients with Ulcerative colitis at the baseline visit (V1), V2, and V3 visits. The incidence of IBD flares will be evaluated in all patients receiving recombinant boosters. This will be quantified by patients who were in clinical remission who develop a disease flare after receiving a recombinant COVID-19 booster.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of participants reporting acute rejection of their transplant</measure>
      <time_frame>up to 6 months</time_frame>
      <description>Participants will be asked if they have been diagnosed with acute rejection after their baseline visit (V1). Episodes of acute rejection will be collected by searching electronic medical records and asking patients at each clinic visit (V2 and V3). Acute rejection will be defined as a notation of a new episode of acute rejection (cellular or antibody-mediated), a steroid bolus and taper in the absence of another indication, or administration of a T or B cell depleting agent or immune globulin. This will be quantified by patients who were who developing acute rejection of their transplant after receiving a recombinant COVID-19 booster.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Immunosuppression</condition>
    <condition>COVID-19</condition>
    <arm_group>
      <arm_group_label>Participants who have had Solid Organ Transplants</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Male and females aged 18 to 85 who are solid organ transplant recipients and receive the study intervention.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Participants with IBD</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Male and females aged 18 to 85 who have IBD and receive the study intervention.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>NVX-CoV2372</intervention_name>
      <description>Novavax COVID-19 Vaccine Booster for Omicron XBB.1.5</description>
      <arm_group_label>Participants who have had Solid Organ Transplants</arm_group_label>
      <arm_group_label>Participants with IBD</arm_group_label>
      <other_name>Novavax COVID-19 Vaccine</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          • Patient has a history of ulcerative colitis (UC) or Crohn's disease diagnosed by standard&#xD;
          clinical, radiographic, endoscopic, and histopathologic criteria.&#xD;
  &#xD;
          or patient is a solid organ transplant recipient (e.g. lung, kidney, liver)&#xD;
  &#xD;
            -  Have received at least three doses of a COVID-19 vaccine.&#xD;
  &#xD;
            -  On one of the following treatment regimens&#xD;
  &#xD;
                 -  IBD&#xD;
  &#xD;
                      -  Thiopurine Therapy Group: on azathioprine at least 2.0mg/kg or 6MP 1.0mg/kg&#xD;
  &#xD;
                      -  Anti-TNF Therapy Group: on maintenance therapy infliximab (at least 8 every&#xD;
                         8 weeks), golimumab (at least monthly), adalimumab (at least every 2 weeks),&#xD;
                         or certolizumab (at least monthly)&#xD;
  &#xD;
                      -  Anti-TNF Combination Therapy Group: on anti-TNF therapy as described above&#xD;
                         along with either 15mg of methotrexate or azathioprine at least 1.0mg/kg or&#xD;
                         6MP 0.5mg/kg.&#xD;
  &#xD;
                      -  Vedolizumab Therapy Group: either vedolizumab monotherapy every 8 week&#xD;
                         dosing or combination therapy Group: on vedolizumab therapy at with&#xD;
                         azathioprine or methotrexate&#xD;
  &#xD;
                      -  Ustekinumab Therapy Group: either ustekinumab monotherapy or combination&#xD;
                         therapy with methotrexate or azathioprine.&#xD;
  &#xD;
                      -  Tofacitinib Therapy Group: on tofacitinib at least 5mg orally, twice per day&#xD;
  &#xD;
                      -  Risankizumab Therapy: 360mg every 8 weeks&#xD;
  &#xD;
                      -  Upadactinib Therapy Group: on upadactinib at least 15mg orally&#xD;
  &#xD;
                      -  Ozanimod: 0.92mg once daily&#xD;
  &#xD;
                      -  Corticosteroid Therapy Group: on any one of the therapies above and stable&#xD;
                         doses of corticosteroids&#xD;
  &#xD;
                 -  Solid organ transplant recipient (on any dose of the following regimens: patients&#xD;
                    can be on more than one of the regimens below)&#xD;
  &#xD;
                      -  Mycophenolate&#xD;
  &#xD;
                      -  Tacrolimus or cyclosporine&#xD;
  &#xD;
                      -  Sirolimus or everolimus&#xD;
  &#xD;
                      -  Azathioprine&#xD;
  &#xD;
                      -  Corticosteroids&#xD;
  &#xD;
                      -  Belatacept&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Allergy to recombinant COVID-19 vaccine or any component of it&#xD;
  &#xD;
            -  Patient cannot or will not provide written informed consent.&#xD;
  &#xD;
            -  Unable to provide appropriate informed consent because of illiteracy or impairment in&#xD;
               decision-making capacity.&#xD;
  &#xD;
            -  Active antibody-mediated or cellular rejection.&#xD;
  &#xD;
            -  Recent IBD flare requiring initiation of systemic corticosteroids within the past&#xD;
               month.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Freddy Caldera, DO, MS</last_name>
      <role>Principal Investigator</role>
      <affiliation>UW School of Medicine and Public Health</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Clinical Trials Institute</last_name>
      <phone>608.265.3132</phone>
      <email>info@clinicaltrials.wisc.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>UW School of Medicine and Public Health</name>
        <address>
          <city>Madison</city>
          <state>Wisconsin</state>
          <zip>53792</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Immunogenicity</keyword>
    <keyword>IBD</keyword>
    <keyword>solid organ transplant</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>COVID-19</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>
  
  
text: 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/NCT06027229
  org study id: 2023-1208
  secondary id: Protocol Version 8/23/2023
  secondary id: SMPH/MEDICINE/GASTROENT
  nct id: NCT06027229
  lead sponsor: 
  collaborator: 
  is fda regulated drug: Yes
  is fda regulated device: No
  To determine whether providing a recombinant booster COVID-19 vaccine improves sustained
        humoral and cell-mediated immunogenicity against SARS-CoV-2 in immunosuppressed patients with
        Inflammatory Bowel Disease (IBD) and/or solid organ transplant recipients. 120 participants
        will be enrolled and can expect to be on study for 6 months.
  This will be a single-center, prospective, unblinded, non-randomized study of 120
        immunosuppressed patients who are planning to receive a recombinant COVID-19 vaccine booster
        dose as standard of care and are willing to participate in the study. At least 35 patients
        will have inflammatory bowel disease and at least 35 patients will be a solid organ
        transplant recipient. After obtaining informed consent, individuals who meet the inclusion
        criteria and none of the exclusion criteria will be invited to participate in the study.
        Blood samples will be collected from each participant at the baseline visit (V1), at 1 month
        post-booster (V2 visit), and 6 months post-booster (V3).
  
        Aim 1: To determine whether providing a recombinant booster COVID-19 vaccine improves
        sustained humoral and cell-mediated immunogenicity against SARS-CoV-2 in immunosuppressed
        patients with IBD and/or solid organ transplant recipients.
  
        The investigators hypothesize that solid organ transplant recipients receiving a combination
        of immunosuppressive regimens will have lower antibody concentrations than patients with IBD
        because previous work has shown that patients with IBD have higher rates of seroconversion
        than solid organ transplant recipients.
  allocation: Non-Randomized
  intervention model: Single Group Assignment
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Change in Antibody Concentration from Baseline (visit 1) at 1 month (visit 2)
  time frame: baseline and 1 month
  description: Antibody concentrations 1 month after the recombinant vaccine booster (V2) in patients with IBD and solid organ transplant recipients compared to their baseline visit (V1).
  measure: Seropositivity Rates
  time frame: 1 month, 6 months
  description: Seropositive will be defined by positive anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 performed by Labcorp.
  measure: Percent of Participants Seronegative at Baseline and Subsequently Seropositive
  time frame: baseline, 1 month, 6 months
  description: Percentages (and 2-sided 95% Confidence Intervals) of participants who were seronegative at baseline and became seropositive after immunization will be evaluated in each group. For initially seropositive subjects at V1, antibody concentration at post-vaccination (V2) ≥ 4 fold the pre-vaccination antibody concentration.
  measure: Interferon gamma responses at 1 month compared to baseline
  time frame: baseline and 1 month
  description: An interferon gamma response will be considered any measurable response
  measure: Interferon gamma responses at 6 months compared to 1 month
  time frame: 1 month, 6 months
  description: An interferon gamma response will be considered any measurable response
  measure: Solicited Adverse Events (AEs)
  time frame: up to 7 days on study
  description: The number of participants reporting each solicited local AE and each solicited systemic AE within seven days (Days 1-7) after the booster dose and overall will be summarized for both study groups.
  Solicited local AEs included injection site pain, redness, and swelling.
  Solicited systemic AEs included fatigue, myalgia, arthralgia, headache, shivering/chills, fever, and gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain).
  measure: Unsolicited Adverse Events
  time frame: up to 30 days on study
  description: The number of participants reporting unsolicited AEs within 30 days (Days 1-30) after the booster dose and overall will be summarized for both the study groups.
  measure: Potential Immune-Mediated Diseases (pIMDs)
  time frame: up to 6 months
  description: The number of participants reporting pIMDs from the booster dose to the study end will be summarized for both study groups.
  measure: Serious Adverse Events (SAEs)
  time frame: up to 6 months
  description: The number of participants reporting SAEs and fatal SAEs from the booster dose administration to the study end will be summarized for both the study groups.
  measure: Number of participants reporting disease flares of IBD
  time frame: up to 6 months
  description: Disease activity will be assessed by monitoring disease activity using the Short Crohn's Activity Index (SCAI)18 for patients with Crohn's disease or the Simple Clinical Colitis Activity Index (SCCAI) questionnaire for patients with Ulcerative colitis at the baseline visit (V1), V2, and V3 visits. The incidence of IBD flares will be evaluated in all patients receiving recombinant boosters. This will be quantified by patients who were in clinical remission who develop a disease flare after receiving a recombinant COVID-19 booster.
  measure: Number of participants reporting acute rejection of their transplant
  time frame: up to 6 months
  description: Participants will be asked if they have been diagnosed with acute rejection after their baseline visit (V1). Episodes of acute rejection will be collected by searching electronic medical records and asking patients at each clinic visit (V2 and V3). Acute rejection will be defined as a notation of a new episode of acute rejection (cellular or antibody-mediated), a steroid bolus and taper in the absence of another indication, or administration of a T or B cell depleting agent or immune globulin. This will be quantified by patients who were who developing acute rejection of their transplant after receiving a recombinant COVID-19 booster.
  arm group label: Participants who have had Solid Organ Transplants
  arm group type: Experimental
  description: Male and females aged 18 to 85 who are solid organ transplant recipients and receive the study intervention.
  arm group label: Participants with IBD
  arm group type: Experimental
  description: Male and females aged 18 to 85 who have IBD and receive the study intervention.
  intervention type: Biological
  intervention name: NVX-CoV2372
  description: Novavax COVID-19 Vaccine Booster for Omicron XBB.1.5
  arm group label: Participants who have had Solid Organ Transplants
  arm group label: Participants with IBD
  other name: Novavax COVID-19 Vaccine
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 85 Years
  healthy volunteers: No
  last name: Freddy Caldera, DO, MS
  role: Principal Investigator
  affiliation: UW School of Medicine and Public Health
  last name: Clinical Trials Institute
  phone: 608.265.3132
  email: info@clinicaltrials.wisc.edu
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: COVID-19
  mesh term: Vaccines
  sharing ipd: No