<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/NCT03762824</url>
  </required_header>
  <id_info>
    <org_study_id>IPS-BOOSTER</org_study_id>
    <nct_id>NCT03762824</nct_id>
  </id_info>
  <brief_title>Combined Pneumococcal Conjugate and Polysaccharide Vaccination in Inflammatory Rheumatic Disease</brief_title>
  <acronym>IPS-BOOSTER</acronym>
  <official_title>Combined Pneumococcal Conjugate and Polysaccharide Vaccination in Inflammatory Rheumatic Disease. Impact of Antirheumatic Treatment on Antibody Response.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Region Skane</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Region Skane</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 overall objective of this project is to study the influence of modern anti-inflammatory&#xD;
      treatments in established inflammatory rheumatic diseases (IRD) on antibody response elicited&#xD;
      by pneumococcal vaccination using 13-valent conjugate vaccine in combined schedules with&#xD;
      23-valent polysaccharide vaccine. In addition, the aim is to study the clinical aspects of&#xD;
      vaccination regarding: tolerability in immunosuppressed patients with IRD, impact on existing&#xD;
      rheumatic disease, possible association with onset of new autoimmune diseases, long-term&#xD;
      immunity following pneumococcal vaccination and efficacy in preventing invasive pneumococcal&#xD;
      disease. Results from this study are expected to bridge the existing knowledge gap and&#xD;
      contribute to body of evidence needed for recommendations and implementation of vaccination&#xD;
      program in IRD patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 14, 2016</start_date>
  <completion_date type="Actual">December 21, 2020</completion_date>
  <primary_completion_date type="Actual">September 3, 2018</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>2-fold rise in pneumococcal serotype-specific antibody concentration</measure>
    <time_frame>8 weeks after pneumococcal conjugate vaccine and 4-6 weeks after polysaccharide vaccination</time_frame>
    <description>Pneumococcal serotype-specific antibody concentration (12-valent)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Functional antibody response</measure>
    <time_frame>8 weeks after pneumococcal conjugate vaccine and 4-6 weeks after polysaccharide vaccination</time_frame>
    <description>Opsonophagocytosis activity assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-term serotype-specific immunity to pneumococcal disease</measure>
    <time_frame>3 years after vaccination</time_frame>
    <description>Pneumococcal serotype-specific antibody concentration</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">300</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <condition>Systemic Lupus</condition>
  <condition>Sjögren Syndrome</condition>
  <condition>Systemic Vasculitis</condition>
  <condition>Spondyloarthritis</condition>
  <arm_group>
    <arm_group_label>PCV13+PPV23 vaccinated patients</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with different inflammatory rheumatic diseases are immunized with one dose 13-valent pneumococcal conjugate vaccine 0.5 ml i.m., followed by one dose 23-valent pneumococcal polysaccharide vaccine 0.5 ml i.m. after 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PCV13+PPV23 vaccinated controls</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy controls are immunized with one dose 13-valent pneumococcal conjugate vaccine 0.5 ml i.m., followed by one dose 23-valent pneumococcal polysaccharide vaccine 0.5 ml i.m. after 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PPV23-booster to previous PCV-vaccinated patients</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with different inflammatory rheumatic disease previously immunized with one dose PCV7 or PCV13 within another study (see VACCIMIL), are immunized with one dose PPV23 0.5 ml i.m.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PCV13 to previous PPV23-vaccinated patients</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with different inflammatory rheumatic disease previously immunized with one dose PPV23 within another study (see VACCIMIL), are immunized with one dose PCV13 0.5 ml i.m.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PPV23-booster to previous PCV-vaccinated controls</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Healthy controls previously immunized with one dose PCV7 or PCV13 within another study (see VACCIMIL), are immunized with one dose PPV23 0.5 ml i.m.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>13-valent pneumococcal conjugate vaccine</intervention_name>
    <description>Pneumococcal conjugate vaccination during antirheumatic treatment</description>
    <arm_group_label>PCV13 to previous PPV23-vaccinated patients</arm_group_label>
    <arm_group_label>PCV13+PPV23 vaccinated controls</arm_group_label>
    <arm_group_label>PCV13+PPV23 vaccinated patients</arm_group_label>
    <other_name>Prevenar 13</other_name>
    <other_name>PCV13</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>23-valent pneumococcal polysaccharide vaccine</intervention_name>
    <description>Pneumococcal polysaccharide vaccination during antirheumatic treatment</description>
    <arm_group_label>PCV13+PPV23 vaccinated controls</arm_group_label>
    <arm_group_label>PCV13+PPV23 vaccinated patients</arm_group_label>
    <arm_group_label>PPV23-booster to previous PCV-vaccinated controls</arm_group_label>
    <arm_group_label>PPV23-booster to previous PCV-vaccinated patients</arm_group_label>
    <other_name>Pneumovax</other_name>
    <other_name>PPV23</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients with IRD receiving active anti-rheumatic treatments with DMARDs or&#xD;
             biological remedies are offered to participate in the study. The protocol permits&#xD;
             stratification for prednisolone usage.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  known allergy/intolerance of pneumococcal vaccine&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  active infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jehns Martineus, MD</last_name>
    <role>Study Director</role>
    <affiliation>Skåne Universitets sjukhus, dept of rheumatology</affiliation>
  </overall_official>
  <reference>
    <citation>Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002 Sep;46(9):2287-93. doi: 10.1002/art.10524.</citation>
    <PMID>12355475</PMID>
  </reference>
  <reference>
    <citation>Kapetanovic MC, Saxne T, Sjoholm A, Truedsson L, Jonsson G, Geborek P. Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis. Rheumatology (Oxford). 2006 Jan;45(1):106-11. doi: 10.1093/rheumatology/kei193. Epub 2005 Nov 15.</citation>
    <PMID>16287919</PMID>
  </reference>
  <reference>
    <citation>Kapetanovic MC, Roseman C, Jonsson G, Truedsson L, Saxne T, Geborek P. Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors. Arthritis Rheum. 2011 Dec;63(12):3723-32. doi: 10.1002/art.30580.</citation>
    <PMID>21834061</PMID>
  </reference>
  <reference>
    <citation>Nived P, Nagel J, Saxne T, Geborek P, Jonsson G, Skattum L, Kapetanovic MC. Immune response to pneumococcal conjugate vaccine in patients with systemic vasculitis receiving standard of care therapy. Vaccine. 2017 Jun 22;35(29):3639-3646. doi: 10.1016/j.vaccine.2017.05.044. Epub 2017 May 25.</citation>
    <PMID>28552512</PMID>
  </reference>
  <reference>
    <citation>Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012 Oct 12;61(40):816-9.</citation>
    <PMID>23051612</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>March 28, 2023</last_update_submitted>
  <last_update_submitted_qc>March 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pneumococcal Conjugate Vaccine</keyword>
  <keyword>Pneumococcal Disease</keyword>
  <keyword>Immune Response</keyword>
  <keyword>Inflammatory Rheumatic Disease</keyword>
  <keyword>Pneumococcal Polysaccharide Vaccine</keyword>
  <keyword>Immunosuppression</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spondylitis</mesh_term>
    <mesh_term>Rheumatic Diseases</mesh_term>
    <mesh_term>Sjogren's Syndrome</mesh_term>
    <mesh_term>Spondylarthritis</mesh_term>
    <mesh_term>Vasculitis</mesh_term>
    <mesh_term>Systemic Vasculitis</mesh_term>
    <mesh_term>Collagen Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
    <mesh_term>Heptavalent Pneumococcal Conjugate Vaccine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>If requested we will consider sharing unidentified individual patient data</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/NCT03762824
org study id: IPS-BOOSTER
nct id: NCT03762824
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The overall objective of this project is to study the influence of modern anti-inflammatory
      treatments in established inflammatory rheumatic diseases (IRD) on antibody response elicited
      by pneumococcal vaccination using 13-valent conjugate vaccine in combined schedules with
      23-valent polysaccharide vaccine. In addition, the aim is to study the clinical aspects of
      vaccination regarding: tolerability in immunosuppressed patients with IRD, impact on existing
      rheumatic disease, possible association with onset of new autoimmune diseases, long-term
      immunity following pneumococcal vaccination and efficacy in preventing invasive pneumococcal
      disease. Results from this study are expected to bridge the existing knowledge gap and
      contribute to body of evidence needed for recommendations and implementation of vaccination
      program in IRD patients.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: 2-fold rise in pneumococcal serotype-specific antibody concentration
time frame: 8 weeks after pneumococcal conjugate vaccine and 4-6 weeks after polysaccharide vaccination
description: Pneumococcal serotype-specific antibody concentration (12-valent)
measure: Functional antibody response
time frame: 8 weeks after pneumococcal conjugate vaccine and 4-6 weeks after polysaccharide vaccination
description: Opsonophagocytosis activity assay
measure: Long-term serotype-specific immunity to pneumococcal disease
time frame: 3 years after vaccination
description: Pneumococcal serotype-specific antibody concentration
arm group label: PCV13+PPV23 vaccinated patients
arm group type: Active Comparator
description: Patients with different inflammatory rheumatic diseases are immunized with one dose 13-valent pneumococcal conjugate vaccine 0.5 ml i.m., followed by one dose 23-valent pneumococcal polysaccharide vaccine 0.5 ml i.m. after 8 weeks.
arm group label: PCV13+PPV23 vaccinated controls
arm group type: Active Comparator
description: Healthy controls are immunized with one dose 13-valent pneumococcal conjugate vaccine 0.5 ml i.m., followed by one dose 23-valent pneumococcal polysaccharide vaccine 0.5 ml i.m. after 8 weeks.
arm group label: PPV23-booster to previous PCV-vaccinated patients
arm group type: Active Comparator
description: Patients with different inflammatory rheumatic disease previously immunized with one dose PCV7 or PCV13 within another study (see VACCIMIL), are immunized with one dose PPV23 0.5 ml i.m.
arm group label: PCV13 to previous PPV23-vaccinated patients
arm group type: Active Comparator
description: Patients with different inflammatory rheumatic disease previously immunized with one dose PPV23 within another study (see VACCIMIL), are immunized with one dose PCV13 0.5 ml i.m.
arm group label: PPV23-booster to previous PCV-vaccinated controls
arm group type: Active Comparator
description: Healthy controls previously immunized with one dose PCV7 or PCV13 within another study (see VACCIMIL), are immunized with one dose PPV23 0.5 ml i.m.
intervention type: Biological
intervention name: 13-valent pneumococcal conjugate vaccine
description: Pneumococcal conjugate vaccination during antirheumatic treatment
arm group label: PCV13 to previous PPV23-vaccinated patients
arm group label: PCV13+PPV23 vaccinated controls
arm group label: PCV13+PPV23 vaccinated patients
other name: Prevenar 13
other name: PCV13
intervention type: Biological
intervention name: 23-valent pneumococcal polysaccharide vaccine
description: Pneumococcal polysaccharide vaccination during antirheumatic treatment
arm group label: PCV13+PPV23 vaccinated controls
arm group label: PCV13+PPV23 vaccinated patients
arm group label: PPV23-booster to previous PCV-vaccinated controls
arm group label: PPV23-booster to previous PCV-vaccinated patients
other name: Pneumovax
other name: PPV23
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Jehns Martineus, MD
role: Study Director
affiliation: Skåne Universitets sjukhus, dept of rheumatology
citation: Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002 Sep;46(9):2287-93. doi: 10.1002/art.10524.
PMID: 12355475
citation: Kapetanovic MC, Saxne T, Sjoholm A, Truedsson L, Jonsson G, Geborek P. Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis. Rheumatology (Oxford). 2006 Jan;45(1):106-11. doi: 10.1093/rheumatology/kei193. Epub 2005 Nov 15.
PMID: 16287919
citation: Kapetanovic MC, Roseman C, Jonsson G, Truedsson L, Saxne T, Geborek P. Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors. Arthritis Rheum. 2011 Dec;63(12):3723-32. doi: 10.1002/art.30580.
PMID: 21834061
citation: Nived P, Nagel J, Saxne T, Geborek P, Jonsson G, Skattum L, Kapetanovic MC. Immune response to pneumococcal conjugate vaccine in patients with systemic vasculitis receiving standard of care therapy. Vaccine. 2017 Jun 22;35(29):3639-3646. doi: 10.1016/j.vaccine.2017.05.044. Epub 2017 May 25.
PMID: 28552512
citation: Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012 Oct 12;61(40):816-9.
PMID: 23051612
responsible party type: Sponsor
mesh term: Spondylitis
mesh term: Rheumatic Diseases
mesh term: Sjogren's Syndrome
mesh term: Spondylarthritis
mesh term: Vasculitis
mesh term: Systemic Vasculitis
mesh term: Collagen Diseases
mesh term: Vaccines
mesh term: Heptavalent Pneumococcal Conjugate Vaccine
sharing ipd: Undecided
ipd description: If requested we will consider sharing unidentified individual patient data