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/NCT05977127</url>
    </required_header>
    <id_info>
      <org_study_id>2023-503800-99-00</org_study_id>
      <nct_id>NCT05977127</nct_id>
    </id_info>
    <brief_title>Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly</brief_title>
    <acronym>HVaNa</acronym>
    <official_title>Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Radboud University Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Radboud University Medical Center</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>
        Respiratory tract infections, e.g. caused by SARS-CoV-2, disproportionately affect elderly.&#xD;
        Vaccination has shown to be the most cost-effective approach to prevent infections. However,&#xD;
        older adults often fail to induce a potent immune response to vaccines, as was also seen&#xD;
        recently for COVID-19 mRNA vaccines. This is likely due to immune dysfunction as a&#xD;
        consequence of aging. To potentiate a stronger immune response, vaccine administration into&#xD;
        the papillary dermis (intradermal, ID) has been proposed as an alternative strategy to&#xD;
        intramuscular (IM) administration.&#xD;
  &#xD;
        Vaccination through the ID route has shown to be safe and equally or more effective than IM&#xD;
        vaccination with a wide variety of vaccines. Recently, ID administration has been tested with&#xD;
        two COVID-19 mRNA vaccines (Spikevax, Moderna and Comirnaty, Pfizer/BioNTech) in reduced&#xD;
        (fractional) doses of the standard IM dose.&#xD;
  &#xD;
        To ease ID administration and thereby facilitate the implementation of this route,&#xD;
        silicon-based microneedles have been developed. These needles have shown to allow ID&#xD;
        administration of the Spikevax vaccine with equal safety and immunogenicity profiles as the&#xD;
        traditional Mantoux approach in young adults.&#xD;
  &#xD;
        In the present study, we will investigate the immunogenicity of a 20 mcg dose of the COVID-19&#xD;
        mRNA Comirnaty vaccine through ID administration with silicon microneedles in elderly people&#xD;
        (75 years and older), and compare this to immunogenicity of IM administration of a 20 mcg&#xD;
        dose and a 30 mcg (standard IM) dose.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">June 1, 2024</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>
      <intervention_model_description>open-label, randomised, proof-of-concept intervention study</intervention_model_description>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
      <masking_description>Only laboratory personnel is masked. Because of the different administration routes it is not possible to mask the participants or investigators</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Concentrations of SARS-CoV-2-Spike protein specific IgG antibodies in serum for the different intervention groups</measure>
      <time_frame>at 28 days after vaccination</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Titers of SARS-CoV-2 specific neutralising antibodies in serum of the different intervention groups</measure>
      <time_frame>at 28 days after vaccination</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The percentage of participants with local and systemic adverse events</measure>
      <time_frame>up to 28 days after vaccination</time_frame>
      <description>Solicited adverse events (AEs): local reactions, reaction of regional lymph nodes, and systemic reactions up to 14 days following vaccination&#xD;
  Unsolicited AEs up to 28 days following vaccination&#xD;
  Serious AEs (SAEs) up to 28 days following vaccination&#xD;
  Use of antipyretics and analgesics up to 14 days following vaccination</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Concentrations of SARS-CoV-2-Spike protein specific antibodies in serum and mucosal samples for the different intervention groups at various timepoints</measure>
      <time_frame>Day 0, day 28 and month 4 after vaccination</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Titers of SARS-CoV-2 specific neutralising antibodies in serum and mucosal samples of the different intervention groups at various timepoints</measure>
      <time_frame>Day 0, day 28 and month 4 after vaccination</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Changes in expression level of host genes</measure>
      <time_frame>day 0 and day 1 after vaccination</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Cellular responses in blood and mucosal samples at various timepoints</measure>
      <time_frame>Day 0, Day 28, month 4 after vaccination</time_frame>
      <description>e.g. expressed as percentages of immune cell subsets or concentration of cytokines</description>
    </other_outcome>
    <other_outcome>
      <measure>Functional and phenotypic characterization of T cells at various timepoints after vaccination</measure>
      <time_frame>Day 0, Day 28, month 4 after vaccination</time_frame>
      <description>e.g. expressed as percentages of immune cell subsets or concentration of cytokines</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Vaccination; Infection</condition>
    <condition>COVID-19</condition>
    <arm_group>
      <arm_group_label>Intradermal vaccination with 20 mcg mRNA vaccine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will receive a single dose of 20 mcg COVID-19 mRNA vaccine (Comirnaty; Pfizer/BioNTech) through the intradermal route using microneedles.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Intramuscular vaccination with 30 mcg mRNA vaccine</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants will receive a single dose of 30 mcg COVID-19 mRNA vaccine (Comirnaty; Pfizer/BioNTech) through the intramuscular route.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Intramuscular vaccination with 20 mcg mRNA vaccine</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants will receive a single dose of 20 mcg COVID-19 mRNA vaccine (Comirnaty; Pfizer/BioNTech) through the intramuscular route.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Comirnaty</intervention_name>
      <description>Administration of Comirnaty vaccine</description>
      <arm_group_label>Intradermal vaccination with 20 mcg mRNA vaccine</arm_group_label>
      <arm_group_label>Intramuscular vaccination with 20 mcg mRNA vaccine</arm_group_label>
      <arm_group_label>Intramuscular vaccination with 30 mcg mRNA vaccine</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Male or female aged ≥75 years at the moment of immunization.&#xD;
  &#xD;
            -  Healthy, determined by medical history and clinical judgement of the investigator.&#xD;
               Participants with a pre-existing illness that is stable, defined as disease not&#xD;
               requiring significant change in therapy or hospitalisation during the 6 weeks before&#xD;
               enrolment and not expected to require any intervention during the study, can be&#xD;
               included.&#xD;
  &#xD;
            -  Willing and able to comply with all scheduled visits, vaccination plan, laboratory&#xD;
               tests, and other study procedures.&#xD;
  &#xD;
            -  Willing to postpone their regular COVID-19 vaccination upon invitation by the&#xD;
               Municipal Health Service or general practitioner until at least four months after&#xD;
               receiving the intervention.&#xD;
  &#xD;
            -  Completed a primary series of COVID-19 vaccination.&#xD;
  &#xD;
            -  Capable and willing to give personal signed informed consent.&#xD;
  &#xD;
            -  Adequate understanding of the procedures of the study and agrees to abide strictly&#xD;
               thereby.&#xD;
  &#xD;
            -  Fully conversant in the Dutch language.&#xD;
  &#xD;
            -  Agrees his/her general practitioner is informed about participation in the study.&#xD;
  &#xD;
            -  Agrees to provide access to information regarding their vaccination background.&#xD;
  &#xD;
            -  Agrees that the study physician and his/her delegates have access to their medical&#xD;
               file at Radboudumc.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Medical or psychiatric condition that may increase the risk of study participation or,&#xD;
               in the investigator's judgement, make the participant inappropriate for the study.&#xD;
  &#xD;
            -  No decision-making capacity.&#xD;
  &#xD;
            -  History of severe adverse reaction to a vaccine or to any component of the study&#xD;
               intervention.&#xD;
  &#xD;
            -  Thrombose with thrombocytopenia syndrome after vaccination with a COVID-19 vaccine.&#xD;
  &#xD;
            -  Dermatological conditions that might interfere with the ID vaccination.&#xD;
  &#xD;
            -  Receipt of COVID-19 vaccination within 3 months before receiving the study&#xD;
               intervention.&#xD;
  &#xD;
            -  Known or suspected immunodeficiency, as determined by medical history or medication&#xD;
               use (inhalation corticosteroids are allowed).&#xD;
  &#xD;
            -  History of autoimmune disease or an active autoimmune disease requiring therapeutic&#xD;
               intervention.&#xD;
  &#xD;
            -  Bleeding diathesis or condition associated with prolonged bleeding that would, in the&#xD;
               opinion of the investigator, contraindicate IM injection.&#xD;
  &#xD;
            -  Participation in other studies involving other study interventions within 28 days&#xD;
               prior and during 28 days after receiving the study intervention.&#xD;
  &#xD;
            -  Receipt of any other non-study vaccine within 28 days prior and after receiving the&#xD;
               study intervention.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>75 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Hans de Graaf</last_name>
      <role>Principal Investigator</role>
      <affiliation>Stichting Radboud University Medical Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Hans de Graaf</last_name>
      <phone>+31 243614656</phone>
      <email>hans.degraaf@radboudumc.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Lucille van Beek</last_name>
      <phone>+31 243614656</phone>
      <email>lucille.vanbeek@radboudumc.nl</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Radboudumc</name>
        <address>
          <city>Nijmegen</city>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Hans de Graaf</last_name>
        <email>Hans.degraaf@radboudumc.nl</email>
      </contact>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>August 3, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Intradermal</keyword>
    <keyword>COVID-19 mRNA vaccine</keyword>
    <keyword>Elderly</keyword>
    <keyword>Immune response</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>COVID-19</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</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/NCT05977127
  org study id: 2023-503800-99-00
  nct id: NCT05977127
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Respiratory tract infections, e.g. caused by SARS-CoV-2, disproportionately affect elderly.
        Vaccination has shown to be the most cost-effective approach to prevent infections. However,
        older adults often fail to induce a potent immune response to vaccines, as was also seen
        recently for COVID-19 mRNA vaccines. This is likely due to immune dysfunction as a
        consequence of aging. To potentiate a stronger immune response, vaccine administration into
        the papillary dermis (intradermal, ID) has been proposed as an alternative strategy to
        intramuscular (IM) administration.
  
        Vaccination through the ID route has shown to be safe and equally or more effective than IM
        vaccination with a wide variety of vaccines. Recently, ID administration has been tested with
        two COVID-19 mRNA vaccines (Spikevax, Moderna and Comirnaty, Pfizer/BioNTech) in reduced
        (fractional) doses of the standard IM dose.
  
        To ease ID administration and thereby facilitate the implementation of this route,
        silicon-based microneedles have been developed. These needles have shown to allow ID
        administration of the Spikevax vaccine with equal safety and immunogenicity profiles as the
        traditional Mantoux approach in young adults.
  
        In the present study, we will investigate the immunogenicity of a 20 mcg dose of the COVID-19
        mRNA Comirnaty vaccine through ID administration with silicon microneedles in elderly people
        (75 years and older), and compare this to immunogenicity of IM administration of a 20 mcg
        dose and a 30 mcg (standard IM) dose.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: open-label, randomised, proof-of-concept intervention study
  primary purpose: Prevention
  masking: None (Open Label)
  masking description: Only laboratory personnel is masked. Because of the different administration routes it is not possible to mask the participants or investigators
  measure: Concentrations of SARS-CoV-2-Spike protein specific IgG antibodies in serum for the different intervention groups
  time frame: at 28 days after vaccination
  measure: Titers of SARS-CoV-2 specific neutralising antibodies in serum of the different intervention groups
  time frame: at 28 days after vaccination
  measure: The percentage of participants with local and systemic adverse events
  time frame: up to 28 days after vaccination
  description: Solicited adverse events (AEs): local reactions, reaction of regional lymph nodes, and systemic reactions up to 14 days following vaccination
  Unsolicited AEs up to 28 days following vaccination
  Serious AEs (SAEs) up to 28 days following vaccination
  Use of antipyretics and analgesics up to 14 days following vaccination
  measure: Concentrations of SARS-CoV-2-Spike protein specific antibodies in serum and mucosal samples for the different intervention groups at various timepoints
  time frame: Day 0, day 28 and month 4 after vaccination
  measure: Titers of SARS-CoV-2 specific neutralising antibodies in serum and mucosal samples of the different intervention groups at various timepoints
  time frame: Day 0, day 28 and month 4 after vaccination
  measure: Changes in expression level of host genes
  time frame: day 0 and day 1 after vaccination
  measure: Cellular responses in blood and mucosal samples at various timepoints
  time frame: Day 0, Day 28, month 4 after vaccination
  description: e.g. expressed as percentages of immune cell subsets or concentration of cytokines
  measure: Functional and phenotypic characterization of T cells at various timepoints after vaccination
  time frame: Day 0, Day 28, month 4 after vaccination
  description: e.g. expressed as percentages of immune cell subsets or concentration of cytokines
  arm group label: Intradermal vaccination with 20 mcg mRNA vaccine
  arm group type: Experimental
  description: Participants will receive a single dose of 20 mcg COVID-19 mRNA vaccine (Comirnaty; Pfizer/BioNTech) through the intradermal route using microneedles.
  arm group label: Intramuscular vaccination with 30 mcg mRNA vaccine
  arm group type: Active Comparator
  description: Participants will receive a single dose of 30 mcg COVID-19 mRNA vaccine (Comirnaty; Pfizer/BioNTech) through the intramuscular route.
  arm group label: Intramuscular vaccination with 20 mcg mRNA vaccine
  arm group type: Active Comparator
  description: Participants will receive a single dose of 20 mcg COVID-19 mRNA vaccine (Comirnaty; Pfizer/BioNTech) through the intramuscular route.
  intervention type: Biological
  intervention name: Comirnaty
  description: Administration of Comirnaty vaccine
  arm group label: Intradermal vaccination with 20 mcg mRNA vaccine
  arm group label: Intramuscular vaccination with 20 mcg mRNA vaccine
  arm group label: Intramuscular vaccination with 30 mcg mRNA vaccine
  criteria: 
  gender: All
  minimum age: 75 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Hans de Graaf
  role: Principal Investigator
  affiliation: Stichting Radboud University Medical Center
  last name: Hans de Graaf
  phone: +31 243614656
  email: hans.degraaf@radboudumc.nl
  last name: Lucille van Beek
  phone: +31 243614656
  email: lucille.vanbeek@radboudumc.nl
  facility: 
  status: Recruiting
  contact: 
  country: Netherlands
  responsible party type: Sponsor
  mesh term: COVID-19
  sharing ipd: Undecided