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/NCT06028347</url>
    </required_header>
    <id_info>
      <org_study_id>V202_01</org_study_id>
      <nct_id>NCT06028347</nct_id>
    </id_info>
    <brief_title>Safety, Reactogenicity, and Immunogenicity Study of a Self-Amplifying mRNA Influenza Vaccine in Healthy Adults</brief_title>
    <official_title>Phase 1, Randomized, Placebo-Controlled, Observer Blind Study to Evaluate the Safety, Reactogenicity and Immunogenicity of an Investigational Self-Amplifying mRNA Influenza Vaccine in Healthy Adults</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Seqirus</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Seqirus</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>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a Phase 1, first-in-human, randomized, placebo-controlled, observer blind study. The&#xD;
        effect of one or two doses of an investigational vaccine on safety, reactogenicity, kinetics&#xD;
        and magnitude of the post-vaccination antibody response will be evaluated at different&#xD;
        timepoints as compared to placebo in healthy adults.&#xD;
  &#xD;
        Approximately 128 evaluable subjects will be enrolled in this study; n=96 receiving&#xD;
        investigational vaccine and n=32 receiving placebo.&#xD;
  &#xD;
        The study has a screening period (Day -28 to Day -1), a treatment period (Day 1 to Day 43)&#xD;
        and a follow-up period (Day 44 to Day 202).&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 28, 2023</start_date>
    <completion_date type="Anticipated">September 24, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 24, 2024</primary_completion_date>
    <phase>Phase 1</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number and percentage of subjects with clinically significant abnormal vital signs and/or acute reactions</measure>
      <time_frame>up to 60 minutes or within 6 hours post vaccination</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number and percentage of subjects reporting reactogenicity: Solicited local and systemic AEs</measure>
      <time_frame>Day 1 to Day 14 of each post vaccination period</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number and percentage of subjects reporting unsolicited AEs</measure>
      <time_frame>Day 1 to Day 43</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number and percentage of subjects reporting AEs leading to study withdrawal, Adverse Events of Special Interest (AESIs), medically attended AEs (MAAEs), and serious adverse events (SAEs).</measure>
      <time_frame>Day 1 to Day 202</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number and percentage of subjects with Grade 3 or greater abnormal clinically significant hematology and chemistry laboratory values</measure>
      <time_frame>Day 3 to Day 43</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number and percentage of subjects with grading shifts in hematology and chemistry laboratory assessments</measure>
      <time_frame>Day 3 to Day 43</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Serum antibody titer against the HA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via HI assay</measure>
      <time_frame>Day 1, Day 22, Day 43</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number and percentage of subjects with HAI titer ≥1:10 and &lt;1:10 (lower limit of quantification [LLOQ])</measure>
      <time_frame>Day 1, Day 22, Day 43</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Number and percentage of subjects with HAI titer ≥1:40, ≥1:80, ≥1:160 and ≥1:320</measure>
      <time_frame>Day 1, Day 22, Day 43</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Seroconversion rate (SCR) by HAI assay</measure>
      <time_frame>Day 1, Day 22, Day 43</time_frame>
      <description>SCR defined as the percentage of subjects with either a prevaccination HAI titer &lt;1:10 and a post-vaccination HAI titer ≥1:40, or a prevaccination HAI titer ≥1:10 and a ≥4-fold increase in post-vaccination</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Serum antibody titer against the HA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via HI assay</measure>
      <time_frame>Day 1, Day 202</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number and percentage of subjects with ≥4-fold increase in post-vaccination HAI titer</measure>
      <time_frame>Day 1, Day 202</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number and percentage of subjects with HAI titer ≥1:10 and &lt;1:10 (LLOQ)</measure>
      <time_frame>Day 202</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number and percentage of subjects with HAI titer ≥1:40, ≥1:80, ≥1:160 and ≥1:320</measure>
      <time_frame>Day 202</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Seroconversion rate (SCR) by HAI assay</measure>
      <time_frame>Day 1, Day 202</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum antibody titer against the NA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via ELLA assay</measure>
      <time_frame>Day 1, Day 22, Day 43, Day 202</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number and percentage of subjects with ≥4-fold increase in post-vaccination ELLA titer</measure>
      <time_frame>Day 1, Day 22, Day 43, Day 202</time_frame>
    </secondary_outcome>
    <number_of_arms>5</number_of_arms>
    <enrollment type="Anticipated">128</enrollment>
    <condition>Influenza, Human</condition>
    <arm_group>
      <arm_group_label>sa-mRNA vaccine dose 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>sa-mRNA vaccine dose 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>sa-mRNA vaccine dose 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>sa-mRNA vaccine dose 4</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>sa-mRNA vaccine Dose 1</intervention_name>
      <description>self-amplifying mRNA vaccine</description>
      <arm_group_label>sa-mRNA vaccine dose 1</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>sa-mRNA vaccine Dose 2</intervention_name>
      <description>self-amplifying mRNA vaccine</description>
      <arm_group_label>sa-mRNA vaccine dose 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>sa-mRNA vaccine Dose 3</intervention_name>
      <description>self-amplifying mRNA vaccine</description>
      <arm_group_label>sa-mRNA vaccine dose 3</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>sa-mRNA vaccine Dose 4</intervention_name>
      <description>self-amplifying mRNA vaccine</description>
      <arm_group_label>sa-mRNA vaccine dose 4</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Saline for injection</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Individuals 18 to 49 years of age OR 65 to 85 years of age, inclusive on the day of&#xD;
               informed consent.&#xD;
  &#xD;
            2. Individuals with body mass index (BMI) between 18 and 32 kg/m2, inclusive, at&#xD;
               screening .&#xD;
  &#xD;
            3. Individuals who can comply with study procedures including follow-up .&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Female participants of childbearing potential who are pregnant, lactating, or who have&#xD;
               not adhered to a specified set of highly effective contraceptive methods from at least&#xD;
               30 days prior to informed consent and who do not plan to do so for the duration of the&#xD;
               study.&#xD;
  &#xD;
            2. Male participants who have not adhered to using barrier contraception such as a condom&#xD;
               during at least 60 days after each vaccination, to prevent semen transfer to their&#xD;
               sexual partners and prevent pregnancy of a female partner.&#xD;
  &#xD;
            3. Progressive, unstable, or uncontrolled clinical conditions&#xD;
  &#xD;
            4. Known hypersensitivity or allergy to any study vaccine component&#xD;
  &#xD;
            5. Known history of Guillain-Barré syndrome or other demyelinating disease&#xD;
  &#xD;
            6. Condition representing a contraindication to vaccination or blood draw&#xD;
  &#xD;
            7. Abnormal function of immune system due to clinical condition, medications, or&#xD;
               radiotherapy.&#xD;
  &#xD;
            8. Receipt or planning to receive blood products, non-study vaccine, influenza vaccine,&#xD;
               mRNA-platform vaccine within different timeframes; previous or from study vaccination.&#xD;
  &#xD;
            9. Baseline abnormal clinically significant ECG, laboratory safety parameters or vital&#xD;
               signs.&#xD;
  &#xD;
           10. Plan to donate blood products (other than for this study), sperm, ova, tissues, or&#xD;
               organs up to 60 days following the last vaccination.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Clinical Program Director</last_name>
      <role>Study Director</role>
      <affiliation>Seqirus</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Clinical Trial Disclosure Manager</last_name>
      <phone>+1 855 358 8966</phone>
      <email>seqirus.clinicaltrials@seqirus.com</email>
    </overall_contact>
    <verification_date>September 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 8, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Influenza</keyword>
    <keyword>Vaccine</keyword>
    <keyword>mRNA</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Influenza, Human</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>Yes</sharing_ipd>
      <ipd_description>SEQIRUS supports the release of anonymized subject-level and study-level data in compliance with regulatory requirements, including Clinical Documents which are part of the CTD modules submitted to regulatory agencies for public release.&#xD;
  Summary results disclosure is either in document form (e.g., ICH E3 Clinical Study Report synopsis) or structured data form (such as summary results in ClinicalTrials.gov (United States) or eudract.ema.europa.eu (EU Clinical Trial Registry [EU CTR])).</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_time_frame>SEQIRUS discloses results from clinical studies within 12 months of last patient last visit (LPLV) unless otherwise mandated by local laws or regulations.</ipd_time_frame>
      <ipd_access_criteria>SEQIRUS will consider requests from qualified scientific and medical researchers to disclose protocols, anonymized subject-level data and study-level data when there is medical, scientific and/or public health interest to ensure the safe use of a Seqirus product licensed on or after 1 January 2014 in the United States (US) and/or the European Union (EU). This applies to Seqirus-sponsored interventional studies initiated after 27 September 2007 and ongoing as of 26 December 2007, that have been included as part of a US or EU submission package which received approval in US and EU on or after 1 January 2014 and have been accepted for publication.</ipd_access_criteria>
      <ipd_url>http://www.seqirus.us/partnering</ipd_url>
    </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/NCT06028347
  org study id: V202_01
  nct id: NCT06028347
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  This is a Phase 1, first-in-human, randomized, placebo-controlled, observer blind study. The
        effect of one or two doses of an investigational vaccine on safety, reactogenicity, kinetics
        and magnitude of the post-vaccination antibody response will be evaluated at different
        timepoints as compared to placebo in healthy adults.
  
        Approximately 128 evaluable subjects will be enrolled in this study; n=96 receiving
        investigational vaccine and n=32 receiving placebo.
  
        The study has a screening period (Day -28 to Day -1), a treatment period (Day 1 to Day 43)
        and a follow-up period (Day 44 to Day 202).
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Number and percentage of subjects with clinically significant abnormal vital signs and/or acute reactions
  time frame: up to 60 minutes or within 6 hours post vaccination
  measure: Number and percentage of subjects reporting reactogenicity: Solicited local and systemic AEs
  time frame: Day 1 to Day 14 of each post vaccination period
  measure: Number and percentage of subjects reporting unsolicited AEs
  time frame: Day 1 to Day 43
  measure: Number and percentage of subjects reporting AEs leading to study withdrawal, Adverse Events of Special Interest (AESIs), medically attended AEs (MAAEs), and serious adverse events (SAEs).
  time frame: Day 1 to Day 202
  measure: Number and percentage of subjects with Grade 3 or greater abnormal clinically significant hematology and chemistry laboratory values
  time frame: Day 3 to Day 43
  measure: Number and percentage of subjects with grading shifts in hematology and chemistry laboratory assessments
  time frame: Day 3 to Day 43
  measure: Serum antibody titer against the HA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via HI assay
  time frame: Day 1, Day 22, Day 43
  measure: Number and percentage of subjects with HAI titer ≥1:10 and <1:10 (lower limit of quantification [LLOQ])
  time frame: Day 1, Day 22, Day 43
  measure: Number and percentage of subjects with HAI titer ≥1:40, ≥1:80, ≥1:160 and ≥1:320
  time frame: Day 1, Day 22, Day 43
  measure: Seroconversion rate (SCR) by HAI assay
  time frame: Day 1, Day 22, Day 43
  description: SCR defined as the percentage of subjects with either a prevaccination HAI titer <1:10 and a post-vaccination HAI titer ≥1:40, or a prevaccination HAI titer ≥1:10 and a ≥4-fold increase in post-vaccination
  measure: Serum antibody titer against the HA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via HI assay
  time frame: Day 1, Day 202
  measure: Number and percentage of subjects with ≥4-fold increase in post-vaccination HAI titer
  time frame: Day 1, Day 202
  measure: Number and percentage of subjects with HAI titer ≥1:10 and <1:10 (LLOQ)
  time frame: Day 202
  measure: Number and percentage of subjects with HAI titer ≥1:40, ≥1:80, ≥1:160 and ≥1:320
  time frame: Day 202
  measure: Seroconversion rate (SCR) by HAI assay
  time frame: Day 1, Day 202
  measure: Serum antibody titer against the NA glycoprotein in terms of GMT, GMFI, and GMT ratio measured via ELLA assay
  time frame: Day 1, Day 22, Day 43, Day 202
  measure: Number and percentage of subjects with ≥4-fold increase in post-vaccination ELLA titer
  time frame: Day 1, Day 22, Day 43, Day 202
  arm group label: sa-mRNA vaccine dose 1
  arm group type: Experimental
  arm group label: sa-mRNA vaccine dose 2
  arm group type: Experimental
  arm group label: sa-mRNA vaccine dose 3
  arm group type: Experimental
  arm group label: sa-mRNA vaccine dose 4
  arm group type: Experimental
  arm group label: Placebo
  arm group type: Placebo Comparator
  intervention type: Biological
  intervention name: sa-mRNA vaccine Dose 1
  description: self-amplifying mRNA vaccine
  arm group label: sa-mRNA vaccine dose 1
  intervention type: Biological
  intervention name: sa-mRNA vaccine Dose 2
  description: self-amplifying mRNA vaccine
  arm group label: sa-mRNA vaccine dose 2
  intervention type: Biological
  intervention name: sa-mRNA vaccine Dose 3
  description: self-amplifying mRNA vaccine
  arm group label: sa-mRNA vaccine dose 3
  intervention type: Biological
  intervention name: sa-mRNA vaccine Dose 4
  description: self-amplifying mRNA vaccine
  arm group label: sa-mRNA vaccine dose 4
  intervention type: Biological
  intervention name: Placebo
  description: Saline for injection
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 85 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Clinical Program Director
  role: Study Director
  affiliation: Seqirus
  last name: Clinical Trial Disclosure Manager
  phone: +1 855 358 8966
  email: seqirus.clinicaltrials@seqirus.com
  responsible party type: Sponsor
  mesh term: Influenza, Human
  mesh term: Vaccines
  sharing ipd: Yes
  ipd description: SEQIRUS supports the release of anonymized subject-level and study-level data in compliance with regulatory requirements, including Clinical Documents which are part of the CTD modules submitted to regulatory agencies for public release.
  Summary results disclosure is either in document form (e.g., ICH E3 Clinical Study Report synopsis) or structured data form (such as summary results in ClinicalTrials.gov (United States) or eudract.ema.europa.eu (EU Clinical Trial Registry [EU CTR])).
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd time frame: SEQIRUS discloses results from clinical studies within 12 months of last patient last visit (LPLV) unless otherwise mandated by local laws or regulations.
  ipd access criteria: SEQIRUS will consider requests from qualified scientific and medical researchers to disclose protocols, anonymized subject-level data and study-level data when there is medical, scientific and/or public health interest to ensure the safe use of a Seqirus product licensed on or after 1 January 2014 in the United States (US) and/or the European Union (EU). This applies to Seqirus-sponsored interventional studies initiated after 27 September 2007 and ongoing as of 26 December 2007, that have been included as part of a US or EU submission package which received approval in US and EU on or after 1 January 2014 and have been accepted for publication.
  ipd url: http://www.seqirus.us/partnering