<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/NCT03277703</url>
  </required_header>
  <id_info>
    <org_study_id>1077651</org_study_id>
    <nct_id>NCT03277703</nct_id>
  </id_info>
  <brief_title>Flu Vaccine Response in Patients on Biologic Therapies</brief_title>
  <official_title>Booster Vaccine Strategy to Improve Serologic Responses to Influenza Vaccination in Children With Rheumatic Diseases and Inflammatory Bowel Disease Who Are Receiving Immunosuppressive Therapies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stony Brook University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Stony Brook University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This proposed study will assess the immunogenicity, safety, and clinical efficacy of an&#xD;
      influenza vaccine booster dose strategy in patients with autoimmune diseases who are&#xD;
      receiving immunosuppressive therapies. Investigators will compare serologic responses to&#xD;
      single versus a booster dose of influenza vaccine in patients with inflammatory bowel disease&#xD;
      (IBD- Crohn's Disease or Ulcerative Colitis) or rheumatologic diseases who are receiving&#xD;
      immunosuppressive therapies. Subjects will be randomized to receive either one or two doses&#xD;
      of influenza vaccination in year #1. In year# 2, all participants will be given two doses of&#xD;
      influenza vaccine. Serologic responses will be measured pre and 4-6 weeks post vaccination.&#xD;
      This study will also assess the immunogenicity and safety of a booster vaccine strategy in&#xD;
      the prevention of influenza-like illness (ILI). Investigators anticipate that booster dose&#xD;
      strategy will improve both clinical and serologic responses in this vulnerable population.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 3, 2017</start_date>
  <completion_date type="Actual">January 1, 2020</completion_date>
  <primary_completion_date type="Actual">January 1, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Influenza hemagglutination inhibition (HAI) titer</measure>
    <time_frame>4 weeks post vaccination</time_frame>
    <description>immunological vaccine response</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical efficacy of vaccine</measure>
    <time_frame>through study completion, an average of 2 years</time_frame>
    <description>decreased influenza rates</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Rheumatologic Disorder</condition>
  <condition>Inflammatory Bowel Diseases</condition>
  <condition>Immune Complex Diseases</condition>
  <arm_group>
    <arm_group_label>Group 1 - Booster</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 1 subjects will receive a second booster dose of injectable influenza vaccine 4 weeks after initial vaccination in year 1 and year 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 - Standard</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 2 subjects will be receive the standard single dose of influenza vaccine in year 1 but will receive a second booster dose of injectable influenza vaccine 4 weeks after initial vaccination in year 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Influenza vaccine</intervention_name>
    <description>The primary aim of this study is to assess the immunogenicity of booster dose influenza vaccine strategy in patients with rheumatologic diseases and IBD who are receiving immunosuppressive therapies.&#xD;
Secondary aims of this study include assessment of the safety and clinical efficacy, of booster dose influenza vaccine in the prevention of influenza-like illnesses (ILI) in this patient population</description>
    <arm_group_label>Group 1 - Booster</arm_group_label>
    <arm_group_label>Group 2 - Standard</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children ages 3-22 years&#xD;
&#xD;
          -  Rheumatologic condition (JIA, Uveitis, SLE and other rheumatologic disorders) or&#xD;
             inflammatory bowel disease (Crohn's disease or ulcerative colitis) and who are&#xD;
             receiving immunosuppressive therapies as follows:&#xD;
&#xD;
               -  TNF inhibitors [etanercept (Enbrel), adalimumab (Humira®), infliximab&#xD;
                  (Remicade®)]&#xD;
&#xD;
               -  anti IL -1 [anakinra (Kineret®) or canakinumab (Ilaris®)]&#xD;
&#xD;
               -  IL-6 tocilizumab (Actemra®)&#xD;
&#xD;
               -  anti IL-12/23 ustekinumab (Stelara®)&#xD;
&#xD;
               -  anti CTLA-4 [abatacept (Orencia®)]&#xD;
&#xD;
               -  vedolizumab (Entyvio®)&#xD;
&#xD;
               -  azathioprine (Imuran®)&#xD;
&#xD;
               -  6 mercaptopurine (Purinethol®)&#xD;
&#xD;
               -  Cyclosporine&#xD;
&#xD;
               -  Leflunomide&#xD;
&#xD;
               -  Mycophenolate&#xD;
&#xD;
               -  methotrexate (Otrexup® or Rasuvo®)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior allergic reaction to any vaccine components&#xD;
&#xD;
          -  Other contraindication to influenza vaccination&#xD;
&#xD;
          -  Severe egg allergy&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Prior Guillain-Barre syndrome&#xD;
&#xD;
          -  Therapy with oral corticosteroids ≥2 mg/mg/day within 4 weeks of study entry&#xD;
&#xD;
          -  Prior rituximab&#xD;
&#xD;
          -  Prior cyclophosphamide&#xD;
&#xD;
          -  Prior IVIG within 8 weeks&#xD;
&#xD;
          -  Acute febrile illness at time of study evaluation&#xD;
&#xD;
          -  No prior history of two doses of influenza in the past for ages 3-8 years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>22 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Clinical Research Center</name>
      <address>
        <city>East Setauket</city>
        <state>New York</state>
        <zip>11733</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Walters HM, Pan N, Lehman TJ, Adams A, Huang WT, Sitaras L, Cunningham-Rundles S, Walsh TJ, Toussi SS. A prospective study comparing infection risk and disease activity in children with juvenile idiopathic arthritis treated with and without tumor necrosis factor-alpha inhibitors. Clin Rheumatol. 2015 Mar;34(3):457-64. doi: 10.1007/s10067-014-2779-8. Epub 2014 Sep 18.</citation>
    <PMID>25227771</PMID>
  </reference>
  <reference>
    <citation>Toussi SS, Pan N, Walters HM, Walsh TJ. Infections in children and adolescents with juvenile idiopathic arthritis and inflammatory bowel disease treated with tumor necrosis factor-alpha inhibitors: systematic review of the literature. Clin Infect Dis. 2013 Nov;57(9):1318-30. doi: 10.1093/cid/cit489. Epub 2013 Jul 29.</citation>
    <PMID>23899685</PMID>
  </reference>
  <reference>
    <citation>Carvalho LM, de Paula FE, Silvestre RV, Roberti LR, Arruda E, Mello WA, Ferriani VP. Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients. Pediatr Rheumatol Online J. 2013 Mar 7;11:10. doi: 10.1186/1546-0096-11-10. eCollection 2013.</citation>
    <PMID>23510667</PMID>
  </reference>
  <reference>
    <citation>Aikawa NE, Campos LM, Silva CA, Carvalho JF, Saad CG, Trudes G, Duarte A, Miraglia JL, Timenetsky Mdo C, Viana VS, Franca IL, Bonfa E, Pereira RM. Glucocorticoid: major factor for reduced immunogenicity of 2009 influenza A (H1N1) vaccine in patients with juvenile autoimmune rheumatic disease. J Rheumatol. 2012 Jan;39(1):167-73. doi: 10.3899/jrheum.110721. Epub 2011 Nov 15.</citation>
    <PMID>22089462</PMID>
  </reference>
  <reference>
    <citation>Flannery B, Reynolds SB, Blanton L, Santibanez TA, O'Halloran A, Lu PJ, Chen J, Foppa IM, Gargiullo P, Bresee J, Singleton JA, Fry AM. Influenza Vaccine Effectiveness Against Pediatric Deaths: 2010-2014. Pediatrics. 2017 May;139(5):e20164244. doi: 10.1542/peds.2016-4244. Epub 2017 Apr 3.</citation>
    <PMID>28557757</PMID>
  </reference>
  <reference>
    <citation>Ogimi C, Tanaka R, Saitoh A, Oh-Ishi T. Immunogenicity of influenza vaccine in children with pediatric rheumatic diseases receiving immunosuppressive agents. Pediatr Infect Dis J. 2011 Mar;30(3):208-11. doi: 10.1097/INF.0b013e3181f7ce44.</citation>
    <PMID>20861757</PMID>
  </reference>
  <reference>
    <citation>deBruyn J, Fonseca K, Ghosh S, Panaccione R, Gasia MF, Ueno A, Kaplan GG, Seow CH, Wrobel I. Immunogenicity of Influenza Vaccine for Patients with Inflammatory Bowel Disease on Maintenance Infliximab Therapy: A Randomized Trial. Inflamm Bowel Dis. 2016 Mar;22(3):638-47. doi: 10.1097/MIB.0000000000000615.</citation>
    <PMID>26595551</PMID>
  </reference>
  <reference>
    <citation>Cordero E, Roca-Oporto C, Bulnes-Ramos A, Aydillo T, Gavalda J, Moreno A, Torre-Cisneros J, Montejo JM, Fortun J, Munoz P, Sabe N, Farinas MC, Blanes-Julia M, Lopez-Medrano F, Suarez-Benjumea A, Martinez-Atienza J, Rosso-Fernandez C, Perez-Romero P; TRANSGRIPE 1-2 Study Group. Two Doses of Inactivated Influenza Vaccine Improve Immune Response in Solid Organ Transplant Recipients: Results of TRANSGRIPE 1-2, a Randomized Controlled Clinical Trial. Clin Infect Dis. 2017 Apr 1;64(7):829-838. doi: 10.1093/cid/ciw855.</citation>
    <PMID>28362949</PMID>
  </reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>February 23, 2022</last_update_submitted>
  <last_update_submitted_qc>February 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stony Brook University</investigator_affiliation>
    <investigator_full_name>Christy Beneri</investigator_full_name>
    <investigator_title>Assistant Professor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Influenza vaccine</keyword>
  <keyword>Booster dose</keyword>
  <keyword>immunocompromised</keyword>
  <keyword>Biologic therapy</keyword>
  <keyword>Rheumatologic disease</keyword>
  <keyword>inflammatory bowel disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rheumatic Diseases</mesh_term>
    <mesh_term>Intestinal Diseases</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
    <mesh_term>Collagen Diseases</mesh_term>
    <mesh_term>Immune Complex Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT03277703
org study id: 1077651
nct id: NCT03277703
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This proposed study will assess the immunogenicity, safety, and clinical efficacy of an
      influenza vaccine booster dose strategy in patients with autoimmune diseases who are
      receiving immunosuppressive therapies. Investigators will compare serologic responses to
      single versus a booster dose of influenza vaccine in patients with inflammatory bowel disease
      (IBD- Crohn's Disease or Ulcerative Colitis) or rheumatologic diseases who are receiving
      immunosuppressive therapies. Subjects will be randomized to receive either one or two doses
      of influenza vaccination in year #1. In year# 2, all participants will be given two doses of
      influenza vaccine. Serologic responses will be measured pre and 4-6 weeks post vaccination.
      This study will also assess the immunogenicity and safety of a booster vaccine strategy in
      the prevention of influenza-like illness (ILI). Investigators anticipate that booster dose
      strategy will improve both clinical and serologic responses in this vulnerable population.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Influenza hemagglutination inhibition (HAI) titer
time frame: 4 weeks post vaccination
description: immunological vaccine response
measure: Clinical efficacy of vaccine
time frame: through study completion, an average of 2 years
description: decreased influenza rates
arm group label: Group 1 - Booster
arm group type: Experimental
description: Group 1 subjects will receive a second booster dose of injectable influenza vaccine 4 weeks after initial vaccination in year 1 and year 2.
arm group label: Group 2 - Standard
arm group type: Active Comparator
description: Group 2 subjects will be receive the standard single dose of influenza vaccine in year 1 but will receive a second booster dose of injectable influenza vaccine 4 weeks after initial vaccination in year 2.
intervention type: Biological
intervention name: Influenza vaccine
description: The primary aim of this study is to assess the immunogenicity of booster dose influenza vaccine strategy in patients with rheumatologic diseases and IBD who are receiving immunosuppressive therapies.
Secondary aims of this study include assessment of the safety and clinical efficacy, of booster dose influenza vaccine in the prevention of influenza-like illnesses (ILI) in this patient population
arm group label: Group 1 - Booster
arm group label: Group 2 - Standard
criteria: 
gender: All
minimum age: 3 Years
maximum age: 22 Years
healthy volunteers: No
facility: 
country: United States
citation: Walters HM, Pan N, Lehman TJ, Adams A, Huang WT, Sitaras L, Cunningham-Rundles S, Walsh TJ, Toussi SS. A prospective study comparing infection risk and disease activity in children with juvenile idiopathic arthritis treated with and without tumor necrosis factor-alpha inhibitors. Clin Rheumatol. 2015 Mar;34(3):457-64. doi: 10.1007/s10067-014-2779-8. Epub 2014 Sep 18.
PMID: 25227771
citation: Toussi SS, Pan N, Walters HM, Walsh TJ. Infections in children and adolescents with juvenile idiopathic arthritis and inflammatory bowel disease treated with tumor necrosis factor-alpha inhibitors: systematic review of the literature. Clin Infect Dis. 2013 Nov;57(9):1318-30. doi: 10.1093/cid/cit489. Epub 2013 Jul 29.
PMID: 23899685
citation: Carvalho LM, de Paula FE, Silvestre RV, Roberti LR, Arruda E, Mello WA, Ferriani VP. Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients. Pediatr Rheumatol Online J. 2013 Mar 7;11:10. doi: 10.1186/1546-0096-11-10. eCollection 2013.
PMID: 23510667
citation: Aikawa NE, Campos LM, Silva CA, Carvalho JF, Saad CG, Trudes G, Duarte A, Miraglia JL, Timenetsky Mdo C, Viana VS, Franca IL, Bonfa E, Pereira RM. Glucocorticoid: major factor for reduced immunogenicity of 2009 influenza A (H1N1) vaccine in patients with juvenile autoimmune rheumatic disease. J Rheumatol. 2012 Jan;39(1):167-73. doi: 10.3899/jrheum.110721. Epub 2011 Nov 15.
PMID: 22089462
citation: Flannery B, Reynolds SB, Blanton L, Santibanez TA, O'Halloran A, Lu PJ, Chen J, Foppa IM, Gargiullo P, Bresee J, Singleton JA, Fry AM. Influenza Vaccine Effectiveness Against Pediatric Deaths: 2010-2014. Pediatrics. 2017 May;139(5):e20164244. doi: 10.1542/peds.2016-4244. Epub 2017 Apr 3.
PMID: 28557757
citation: Ogimi C, Tanaka R, Saitoh A, Oh-Ishi T. Immunogenicity of influenza vaccine in children with pediatric rheumatic diseases receiving immunosuppressive agents. Pediatr Infect Dis J. 2011 Mar;30(3):208-11. doi: 10.1097/INF.0b013e3181f7ce44.
PMID: 20861757
citation: deBruyn J, Fonseca K, Ghosh S, Panaccione R, Gasia MF, Ueno A, Kaplan GG, Seow CH, Wrobel I. Immunogenicity of Influenza Vaccine for Patients with Inflammatory Bowel Disease on Maintenance Infliximab Therapy: A Randomized Trial. Inflamm Bowel Dis. 2016 Mar;22(3):638-47. doi: 10.1097/MIB.0000000000000615.
PMID: 26595551
citation: Cordero E, Roca-Oporto C, Bulnes-Ramos A, Aydillo T, Gavalda J, Moreno A, Torre-Cisneros J, Montejo JM, Fortun J, Munoz P, Sabe N, Farinas MC, Blanes-Julia M, Lopez-Medrano F, Suarez-Benjumea A, Martinez-Atienza J, Rosso-Fernandez C, Perez-Romero P; TRANSGRIPE 1-2 Study Group. Two Doses of Inactivated Influenza Vaccine Improve Immune Response in Solid Organ Transplant Recipients: Results of TRANSGRIPE 1-2, a Randomized Controlled Clinical Trial. Clin Infect Dis. 2017 Apr 1;64(7):829-838. doi: 10.1093/cid/ciw855.
PMID: 28362949
responsible party type: Principal Investigator
investigator affiliation: Stony Brook University
investigator full name: Christy Beneri
investigator title: Assistant Professor of Pediatrics
mesh term: Rheumatic Diseases
mesh term: Intestinal Diseases
mesh term: Inflammatory Bowel Diseases
mesh term: Collagen Diseases
mesh term: Immune Complex Diseases