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/NCT06025487</url>
    </required_header>
    <id_info>
      <org_study_id>MenB_Asplenia</org_study_id>
      <secondary_id>2022-001451-16</secondary_id>
      <nct_id>NCT06025487</nct_id>
    </id_info>
    <brief_title>Meningococcal B Vaccine in Patients With Asplenia</brief_title>
    <official_title>Immunogenicity and Safety of a Meningococcal Serogroup B Vaccine in Adult Patients With Asplenia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Medical University of Vienna</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Medical University of Vienna</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>
        Patients without a spleen (asplenia) experience an increased risk for septicaemia from&#xD;
        encapsulated bacteria, which is associated with a high mortality rate. Meningococcal bacteria&#xD;
        can cause such infections and serogroup B is the dominant meningococcal subtype in Europe.&#xD;
        Therefore, vaccination for risk populations like patients without a spleen is a pressing&#xD;
        matter. Considering the effectiveness of the meningococcal serogroup B vaccine, data for this&#xD;
        high-at-risk population is currently lacking. The aim of this study is to evaluate the&#xD;
        meningococcal B vaccine (BEXSERO®) in patients without a spleen compared to a healthy control&#xD;
        group. A total of 40 patients and 40 healthy persons will receive a two-dose schedule of&#xD;
        BEXSERO® with a one-month interval between doses. The effectiveness of the vaccine will be&#xD;
        determined by measuring antibodies against different meningococcal strains in the blood of&#xD;
        the patient. The amount of antibodies one month after second vaccination will be compared&#xD;
        between patients and healthy persons. The most reliable assay to determine antibodies against&#xD;
        meningococcal strains is the human serum bactericidal assay which will be carried out in a&#xD;
        reference laboratory. Other end points are the persistence of antibodies after six months and&#xD;
        the cellular immune response. The cellular immune response will be assessed by measuring the&#xD;
        proliferation of certain immune cells like lymphocytes and the amount of produced cytokines&#xD;
        (signalling proteins) after vaccination. In addition, the safety of the vaccine will be&#xD;
        evaluated by documenting all adverse reactions to the vaccine. Overall, this study will be&#xD;
        the first to assess the effectiveness of the meningococcal B vaccine in this high-at-risk&#xD;
        population and provide data for vaccination guidelines.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study is a prospective open-label phase II pilot study to assess the immunogenicity and&#xD;
        safety of BEXSERO® in asplenic patients. Patients participating in the study will complete a&#xD;
        total of four study visits. A two dose schedule of BEXSERO® will be applied intramuscularly&#xD;
        with a one month interval between doses. Seropositivity will be assessed at baseline during&#xD;
        the first visit, one month and six months after the second vaccination. Basic demographic&#xD;
        data (gender, age) and medical data (type of asplenia, time of splenectomy, underlying&#xD;
        diseases, concurrent medical conditions, medication etc) will be entered into a case report&#xD;
        form (CRF). During the second and third visit all adverse events will be entered into the CRF&#xD;
        and severe adverse events (SAEs) will be reported accordingly. Patients who have either been&#xD;
        splenectomised or suffer from functional asplenia will be recruited for this study during&#xD;
        their routine vaccination visit at the out-patient ward for infectious diseases of the&#xD;
        Medical University of Vienna. A total of 40 patients and 40 healthy controls will be&#xD;
        recruited for this study. The null hypothesis states that the immunogenicity of the&#xD;
        meningococcal B vaccine is inferior in asplenic patients compared to a healthy control group.&#xD;
        Immunogenicity will be assessed by human serum bactericidal antibody assay (hSBA) against&#xD;
        three vaccine antigens. The human serum bactericidal antibody assay (hSBA) will be carried&#xD;
        out in a reference laboratory (Meningococcal Reference Unit, Health Protection Agency North&#xD;
        West Laboratory, Manchester Royal Infirmary, United Kingdom) to determine functional&#xD;
        antibodies against three meningococcal vaccine antigens: PorA (strain NZ98/254), fHbp (strain&#xD;
        44/76-SL) and NadA (strain 5/99). The hSBA measures complement mediated killing of Neisseria&#xD;
        meningitidis by vaccine-induced antibodies. It is considered as the &quot;gold standard&quot; for&#xD;
        measuring antibody response against meningococcal bacteria. Currently, the detection of&#xD;
        antibodies by hSBA with a titre of ≥1:4 is considered as a correlate for protection against&#xD;
        meningococcal disease. The primary end point is the mean log-titre over the three&#xD;
        meningococcal strains (NZ98/254 for PorA, 5/99 for NadA and 44/76-SL for fHbp) as measured by&#xD;
        the hSBA one month after second vaccination. The non-inferiority margin was set to a 2-fold&#xD;
        titre difference between the geometric mean titre of the asplenic group and the healthy&#xD;
        control group. To investigate cellular immunity following meningococcal vaccination,&#xD;
        lymphocyte proliferation and cytokine detection assays will be used.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">June 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">June 1, 2025</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>Parallel Assignment</intervention_model>
      <intervention_model_description>prospective open-label phase II study comparing patients and healthy controls</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Humoral immunogenicity</measure>
      <time_frame>one month after second vaccination</time_frame>
      <description>Immunogenicity will be assessed by human serum bactericidal antibody assay (hSBA) against three vaccine antigens (PorA, fHbp and NadA). The primary end point is the mean log-titre over the three meningococcal strains (NZ98/254 for PorA, 5/99 for NadA and 44/76-SL for fHbp) as measured by the hSBA one month after second vaccination.&#xD;
  The non-inferiority margin was set to a 2-fold titre difference between the geometric mean titre of the asplenic group and the healthy control group.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Persistence of humoral immunity</measure>
      <time_frame>six months after second vaccination</time_frame>
      <description>The persistence of antibodies six months after second vaccination as measured by hSBA</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cellular immunogenicity - lymphocyte proliferation</measure>
      <time_frame>one month after second vaccination</time_frame>
      <description>The cellular immune response as measured by lymphocyte proliferation assay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cellular Immunogenicity - cytokine levels</measure>
      <time_frame>one month after second vaccination</time_frame>
      <description>The cellular immune response as measured by cytokine levels using Luminex</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse Events</measure>
      <time_frame>four weeks after first and second vaccination</time_frame>
      <description>Evaluation of safety by documenting all adverse events after vaccination</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Splenectomy; Status</condition>
    <arm_group>
      <arm_group_label>Patients</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Asplenic patients receiving two doses of Bexsero (meningococcal B vaccine) with one-month interval between doses</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Healthy controls</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Healthy controls receiving two doses of Bexsero (meningococcal B vaccine) with one-month interval between doses</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Bexsero</intervention_name>
      <description>two doses of Bexsero are applied intramuscularly with a one-month interval between doses</description>
      <arm_group_label>Healthy controls</arm_group_label>
      <arm_group_label>Patients</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          For asplenic patients:&#xD;
  &#xD;
            -  asplenia due to splenectomy or functional asplenia&#xD;
  &#xD;
            -  18 to 60 years of age&#xD;
  &#xD;
            -  if female: have a negative urine pregnancy test result at study entry and agree to&#xD;
               employ adequate birth control measures for the duration of the study&#xD;
  &#xD;
            -  providing written informed consent&#xD;
  &#xD;
          For healthy controls:&#xD;
  &#xD;
            -  18 to 60 years of age&#xD;
  &#xD;
            -  if female: have a negative urine pregnancy test result at study entry and agree to&#xD;
               employ adequate birth control measures for the duration of the study&#xD;
  &#xD;
            -  providing written informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          For asplenic patients:&#xD;
  &#xD;
            -  pregnant or lactating&#xD;
  &#xD;
            -  febrile illness within last two weeks prior to enrolment&#xD;
  &#xD;
            -  allergic reactions to vaccination in past&#xD;
  &#xD;
            -  chemotherapy with Rituximab within last six months or during study period&#xD;
  &#xD;
            -  more than 20mg prednisone per day within last four weeks prior or at the time of&#xD;
               enrolment&#xD;
  &#xD;
            -  previous vaccination against meningococcal serogroup B&#xD;
  &#xD;
          For healthy controls:&#xD;
  &#xD;
            -  pregnant or lactating&#xD;
  &#xD;
            -  febrile illness within last two weeks prior to enrolment&#xD;
  &#xD;
            -  allergic reactions to vaccination in past&#xD;
  &#xD;
            -  any immunosuppressive condition or medication&#xD;
  &#xD;
            -  previous vaccination against meningococcal serogroup B&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Nicole Harrison, Dr.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Medical University Vienna</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Nicole Harrison, Dr.</last_name>
      <phone>+43 1 40400</phone>
      <phone_ext>44400</phone_ext>
      <email>nicole.harrison@meduniwien.ac.at</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
      <investigator_full_name>Nicole Harrison</investigator_full_name>
      <investigator_title>Dr. Nicole Harrison, Consultant for Infectious Diseases and Tropical Medicine</investigator_title>
    </responsible_party>
    <keyword>Asplenia</keyword>
    <keyword>Meningococcal disease</keyword>
    <keyword>Meningococcal B vaccine</keyword>
    <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/NCT06025487
  org study id: MenB_Asplenia
  secondary id: 2022-001451-16
  nct id: NCT06025487
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Patients without a spleen (asplenia) experience an increased risk for septicaemia from
        encapsulated bacteria, which is associated with a high mortality rate. Meningococcal bacteria
        can cause such infections and serogroup B is the dominant meningococcal subtype in Europe.
        Therefore, vaccination for risk populations like patients without a spleen is a pressing
        matter. Considering the effectiveness of the meningococcal serogroup B vaccine, data for this
        high-at-risk population is currently lacking. The aim of this study is to evaluate the
        meningococcal B vaccine (BEXSERO®) in patients without a spleen compared to a healthy control
        group. A total of 40 patients and 40 healthy persons will receive a two-dose schedule of
        BEXSERO® with a one-month interval between doses. The effectiveness of the vaccine will be
        determined by measuring antibodies against different meningococcal strains in the blood of
        the patient. The amount of antibodies one month after second vaccination will be compared
        between patients and healthy persons. The most reliable assay to determine antibodies against
        meningococcal strains is the human serum bactericidal assay which will be carried out in a
        reference laboratory. Other end points are the persistence of antibodies after six months and
        the cellular immune response. The cellular immune response will be assessed by measuring the
        proliferation of certain immune cells like lymphocytes and the amount of produced cytokines
        (signalling proteins) after vaccination. In addition, the safety of the vaccine will be
        evaluated by documenting all adverse reactions to the vaccine. Overall, this study will be
        the first to assess the effectiveness of the meningococcal B vaccine in this high-at-risk
        population and provide data for vaccination guidelines.
  This study is a prospective open-label phase II pilot study to assess the immunogenicity and
        safety of BEXSERO® in asplenic patients. Patients participating in the study will complete a
        total of four study visits. A two dose schedule of BEXSERO® will be applied intramuscularly
        with a one month interval between doses. Seropositivity will be assessed at baseline during
        the first visit, one month and six months after the second vaccination. Basic demographic
        data (gender, age) and medical data (type of asplenia, time of splenectomy, underlying
        diseases, concurrent medical conditions, medication etc) will be entered into a case report
        form (CRF). During the second and third visit all adverse events will be entered into the CRF
        and severe adverse events (SAEs) will be reported accordingly. Patients who have either been
        splenectomised or suffer from functional asplenia will be recruited for this study during
        their routine vaccination visit at the out-patient ward for infectious diseases of the
        Medical University of Vienna. A total of 40 patients and 40 healthy controls will be
        recruited for this study. The null hypothesis states that the immunogenicity of the
        meningococcal B vaccine is inferior in asplenic patients compared to a healthy control group.
        Immunogenicity will be assessed by human serum bactericidal antibody assay (hSBA) against
        three vaccine antigens. The human serum bactericidal antibody assay (hSBA) will be carried
        out in a reference laboratory (Meningococcal Reference Unit, Health Protection Agency North
        West Laboratory, Manchester Royal Infirmary, United Kingdom) to determine functional
        antibodies against three meningococcal vaccine antigens: PorA (strain NZ98/254), fHbp (strain
        44/76-SL) and NadA (strain 5/99). The hSBA measures complement mediated killing of Neisseria
        meningitidis by vaccine-induced antibodies. It is considered as the "gold standard" for
        measuring antibody response against meningococcal bacteria. Currently, the detection of
        antibodies by hSBA with a titre of ≥1:4 is considered as a correlate for protection against
        meningococcal disease. The primary end point is the mean log-titre over the three
        meningococcal strains (NZ98/254 for PorA, 5/99 for NadA and 44/76-SL for fHbp) as measured by
        the hSBA one month after second vaccination. The non-inferiority margin was set to a 2-fold
        titre difference between the geometric mean titre of the asplenic group and the healthy
        control group. To investigate cellular immunity following meningococcal vaccination,
        lymphocyte proliferation and cytokine detection assays will be used.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  intervention model description: prospective open-label phase II study comparing patients and healthy controls
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Humoral immunogenicity
  time frame: one month after second vaccination
  description: Immunogenicity will be assessed by human serum bactericidal antibody assay (hSBA) against three vaccine antigens (PorA, fHbp and NadA). The primary end point is the mean log-titre over the three meningococcal strains (NZ98/254 for PorA, 5/99 for NadA and 44/76-SL for fHbp) as measured by the hSBA one month after second vaccination.
  The non-inferiority margin was set to a 2-fold titre difference between the geometric mean titre of the asplenic group and the healthy control group.
  measure: Persistence of humoral immunity
  time frame: six months after second vaccination
  description: The persistence of antibodies six months after second vaccination as measured by hSBA
  measure: Cellular immunogenicity - lymphocyte proliferation
  time frame: one month after second vaccination
  description: The cellular immune response as measured by lymphocyte proliferation assay
  measure: Cellular Immunogenicity - cytokine levels
  time frame: one month after second vaccination
  description: The cellular immune response as measured by cytokine levels using Luminex
  measure: Adverse Events
  time frame: four weeks after first and second vaccination
  description: Evaluation of safety by documenting all adverse events after vaccination
  arm group label: Patients
  arm group type: Active Comparator
  description: Asplenic patients receiving two doses of Bexsero (meningococcal B vaccine) with one-month interval between doses
  arm group label: Healthy controls
  arm group type: Active Comparator
  description: Healthy controls receiving two doses of Bexsero (meningococcal B vaccine) with one-month interval between doses
  intervention type: Biological
  intervention name: Bexsero
  description: two doses of Bexsero are applied intramuscularly with a one-month interval between doses
  arm group label: Healthy controls
  arm group label: Patients
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Nicole Harrison, Dr.
  role: Principal Investigator
  affiliation: Medical University Vienna
  last name: Nicole Harrison, Dr.
  phone: +43 1 40400
  phone ext: 44400
  email: nicole.harrison@meduniwien.ac.at
  responsible party type: Principal Investigator
  investigator affiliation: Medical University of Vienna
  investigator full name: Nicole Harrison
  investigator title: Dr. Nicole Harrison, Consultant for Infectious Diseases and Tropical Medicine
  sharing ipd: No