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/NCT06028841</url>
    </required_header>
    <id_info>
      <org_study_id>VLA1553-304</org_study_id>
      <nct_id>NCT06028841</nct_id>
    </id_info>
    <brief_title>A Clinical Phase 3 Study of VLA1553 in Adult Participants With Human Immunodeficiency Virus (HIV)</brief_title>
    <official_title>An Open-label Phase 3 Study to Assess the Safety and Immunogenicity of a Live-attenuated Chikungunya Virus Vaccine Candidate (VLA1553) in Moderately Immunocompromised Adult Participants Infected With Human Immunodeficiency Virus</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Valneva Austria GmbH</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Valneva Austria GmbH</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a phase 3 clinical study to evaluate the safety, tolerability, and immunogenicity of&#xD;
        VLA1553 in moderately immunocompromised adults with HIV infection.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a multicenter, prospective, open-label, uncontrolled, single arm, phase 3 clinical&#xD;
        study evaluating the final dose of VLA1553. The safety, tolerability, and immunogenicity of&#xD;
        VLA1553 will be assessed in moderately immunocompromised adult participants infected with HIV&#xD;
        living in CHIKV endemic areas. Approximately 75 male and female adults (aged 18 years or&#xD;
        above) infected with HIV will be enrolled. Participants will be screened by ELISA for&#xD;
        evidence of previous CHIKV exposure excluding CHIKV seropositive participants from study&#xD;
        participation.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">January 2025</completion_date>
    <primary_completion_date type="Anticipated">January 2025</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Solicited adverse events</measure>
      <time_frame>until Day 15</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>To assess frequency and severity of unsolicited AEs</measure>
      <time_frame>until Day 29 and Day 180 post-vaccination</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>To assess frequency and relatedness of any serious adverse event (SAE)</measure>
      <time_frame>until Day 180 post-vaccination</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>To assess frequency and severity of any early onset adverse event of special interest (AESI)</measure>
      <time_frame>within 2 to 21 days post-vaccination (i.e. Day 3 - Day 22)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>To assess frequency and severity of any late onset adverse event of special interest (AESI) during the entire study</measure>
      <time_frame>starting 22 days post-vaccination (i.e. Day 23 - Day 180)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>To assess CHIKV viremia</measure>
      <time_frame>on Days 1, 4, 8 and 15 (Day 29 and Day 57, if applicable)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>To assess HIV viral load</measure>
      <time_frame>on Days 1, 15, 29, 57, 85, and 180</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Immune response as measured by CHIKV-specific neutralizing antibody titers post-vaccination as determined by μPRNT assay</measure>
      <time_frame>Day 15, Day 29, Day 57, Day 85 and Day 180</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with seroresponse levels post-vaccination as determined by μPRNT assay</measure>
      <time_frame>Day 15, Day 29, Day 57, Day 85 and Day 180</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants with seroconversion as compared to baseline as determined by μPRNT assay</measure>
      <time_frame>Day 29 and Day 180</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fold increase of CHIKV-specific neutralizing antibody titers determined by μPRNT assay post-vaccination as compared to baseline</measure>
      <time_frame>Day 15, Day 29, Day 57, Day 85 and Day 180</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Proportion of participants reaching an at least 4-fold, 8-fold, 16-fold or 64-fold increase in CHIKV-specific neutralizing antibody titer compared to baseline as measured by μPRNT assay</measure>
      <time_frame>Day 15, Day 29, Day 57, Day 85 and Day 180</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">75</enrollment>
    <condition>Chikungunya Virus Infection</condition>
    <arm_group>
      <arm_group_label>VLA1553</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>VLA1553</intervention_name>
      <description>Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate 1x10E4 TCID50 per dose</description>
      <arm_group_label>VLA1553</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Participants who meet ALL of the following criteria are eligible for this study:&#xD;
  &#xD;
            1. Adult participant aged 18 years or above infected with HIV of either gender&#xD;
  &#xD;
            2. Participant has an understanding of the study and its procedures, agrees to its&#xD;
               provisions, and voluntarily gives written informed consent prior to any study-related&#xD;
               procedures&#xD;
  &#xD;
            3. Stage of disease A1, A2, B1 or B2 according to the revised CDC classification system&#xD;
               for HIV infection from 1993 or Stages 1 or 2 in the absence of AIDS defining&#xD;
               conditions (CDC update from 1994)&#xD;
  &#xD;
            4. Participants are recruited in Cohorts:&#xD;
  &#xD;
                 1. For Cohort I:&#xD;
  &#xD;
                    Participant has CD4+ T cell counts &gt;350-≤400 cells/μL, is receiving&#xD;
                    antiretroviral therapy (ART) for at least 6 months and plasma HIV RNA &lt; 400&#xD;
                    copies/ mL prior enrollment&#xD;
  &#xD;
                 2. For Cohort II:&#xD;
  &#xD;
               Participant has CD4+ T cell counts &gt;200 cells/μL (no upper limit), is receiving ART&#xD;
               for at least 3 months and plasma HIV RNA &lt; 50 copies/ mL prior enrollment&#xD;
  &#xD;
            5. Participant is seronegative for previous CHIKV exposure (i.e. IgM- and IgG-) as&#xD;
               screened by CHIKV-specific ELISA&#xD;
  &#xD;
            6. If female participant is of childbearing potential:&#xD;
  &#xD;
                 1. Participant has a negative urine pregnancy test at screening (Visit 0) or Day 1&#xD;
                    (Visit 1), respectively&#xD;
  &#xD;
                 2. Participant has practiced an adequate method of contraception during the 30 days&#xD;
                    before screening (Visit 0)&#xD;
  &#xD;
                 3. Participant agrees to employ adequate birth control measures for the first three&#xD;
                    months post-vaccination (i.e. until Day 85, Visit 6).&#xD;
  &#xD;
            7. Female/male participant agrees to employ adequate birth control measures for the first&#xD;
               three months post-vaccination (i.e., until Day 85, Visit 7)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Participants who meet ANY of the following criteria are NOT eligible for this study:&#xD;
  &#xD;
            1. Participant is taking medication or other treatment for unresolved symptoms attributed&#xD;
               to a previous CHIKV infection; or has participated in a clinical study involving an&#xD;
               investigational CHIKV vaccine&#xD;
  &#xD;
            2. Participant has an acute or recent infection (and who is not symptom-free in the week&#xD;
               prior to the Screening Visit (Visit 0) and Visit 1)&#xD;
  &#xD;
            3. Participant tests positive for human immunodeficiency virus (HIV) and fulfills AIDS&#xD;
               indicator T cell counts or AIDS indicator conditions (disease stages C1, C2 or C3 or&#xD;
               stage&#xD;
  &#xD;
            4. Participant tests positive for HIV with the actual target disease stages A1, A2, B1 or&#xD;
               B2 (or stage 1 or 2), but was classified in the past at least once as fulfilling AIDS&#xD;
               indicator conditions (disease stage C1, C2 or C3) or AIDS indicator T cell counts&#xD;
               (CD4+ lymphocyte count &lt;200/μL or CD4+ percentage &lt;14%)&#xD;
  &#xD;
            5. Participant tests PCR positive for active hepatitis B or hepatitis C virus (HCV)&#xD;
  &#xD;
            6. Participant has received any vaccine within 28 days prior to vaccination in this study&#xD;
               or plans to receive any vaccine within 28 days after vaccination&#xD;
  &#xD;
            7. Participant has abnormal findings in any required study investigations (e.g. medical&#xD;
               history, physical examination, and laboratory findings) considered clinically relevant&#xD;
               by the Investigator and which pose a risk for participation in the study based on&#xD;
               his/her judgement&#xD;
  &#xD;
            8. Participant currently has or had a history of significant cardiovascular, respiratory,&#xD;
               metabolic, neurological, hepatic, rheumatic, autoimmune, hematological,&#xD;
               gastrointestinal or renal disorder (of note: Mild asthma that requires low dose&#xD;
               corticosteroid inhalation only, during limited time periods of the year is not an&#xD;
               exclusion criterion)&#xD;
  &#xD;
            9. Participant has an abnormal, clinically significant 12-lead ECG at screening&#xD;
  &#xD;
           10. Participant has a history of immune-mediated or clinically relevant&#xD;
               arthritis/arthralgia&#xD;
  &#xD;
           11. Participant has a history of malignancy&#xD;
  &#xD;
           12. Participant has a known or suspected defect of the immune system that can be expected&#xD;
               to influence the immune response to the vaccine other than asymptomatic or moderately&#xD;
               symptomatic HIV infection, such as participants with congenital immunodeficiency,&#xD;
               status post organ transplantation or immuno-suppressive therapy within four weeks&#xD;
               prior to Visit 1. Immuno-suppressive therapy is defined as administration of chronic&#xD;
               (longer than 14 days) prednisone or equivalent ≥0.05 mg/kg/day within 4 weeks prior to&#xD;
               study entry, radiation therapy or immunosuppressive cytotoxic drugs/ monoclonal&#xD;
               antibodies in the previous three years; topical and inhaled steroids are allowed&#xD;
  &#xD;
           13. Participant has a history of any vaccine related contraindicating event (e.g.,&#xD;
               anaphylaxis, allergy to components of the candidate vaccine, other known&#xD;
               contraindications including febrile convulsions)&#xD;
  &#xD;
           14. Participant presents with clinical conditions representing a contraindication to&#xD;
               intramuscular vaccination and blood draws&#xD;
  &#xD;
           15. Participant is pregnant (positive urine pregnancy test at screening or Visit 1,&#xD;
               respectively), is lactating at the time of enrollment, has plans to become pregnant or&#xD;
               subject's female partner plans to become pregnant during the first three months&#xD;
               post-vaccination or practices unreliable contraception&#xD;
  &#xD;
           16. Participant received blood-derived products (e.g. plasma) within 90 days prior to&#xD;
               vaccination in this study&#xD;
  &#xD;
           17. Participant has a rash, dermatological condition or tattoos that would, in the opinion&#xD;
               of the Investigator, interfere with injection site reaction rating&#xD;
  &#xD;
           18. Participant has participated in another clinical study involving an investigational&#xD;
               medicinal product (IMP) or device within 30 days prior to vaccination or is scheduled&#xD;
               to participate in another clinical study involving an IMP, or device during the course&#xD;
               of this study&#xD;
  &#xD;
           19. Participant is a member of the team conducting the study or in a dependent&#xD;
               relationship with one of the study team members. Dependent relationships include close&#xD;
               relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of&#xD;
               the Investigator or site personnel conducting the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Valneva Clinical Development</last_name>
      <role>Study Chair</role>
      <affiliation>Valneva Austria GmbH</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Valneva Clinical Development</last_name>
      <phone>+43 1 206 20</phone>
      <phone_ext>0</phone_ext>
      <email>office@valneva.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>March 29, 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>August 31, 2023</last_update_submitted>
    <last_update_submitted_qc>August 31, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
      <mesh_term>HIV Infections</mesh_term>
      <mesh_term>Chikungunya Fever</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/NCT06028841
  org study id: VLA1553-304
  nct id: NCT06028841
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a phase 3 clinical study to evaluate the safety, tolerability, and immunogenicity of
        VLA1553 in moderately immunocompromised adults with HIV infection.
  This is a multicenter, prospective, open-label, uncontrolled, single arm, phase 3 clinical
        study evaluating the final dose of VLA1553. The safety, tolerability, and immunogenicity of
        VLA1553 will be assessed in moderately immunocompromised adult participants infected with HIV
        living in CHIKV endemic areas. Approximately 75 male and female adults (aged 18 years or
        above) infected with HIV will be enrolled. Participants will be screened by ELISA for
        evidence of previous CHIKV exposure excluding CHIKV seropositive participants from study
        participation.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Solicited adverse events
  time frame: until Day 15
  measure: To assess frequency and severity of unsolicited AEs
  time frame: until Day 29 and Day 180 post-vaccination
  measure: To assess frequency and relatedness of any serious adverse event (SAE)
  time frame: until Day 180 post-vaccination
  measure: To assess frequency and severity of any early onset adverse event of special interest (AESI)
  time frame: within 2 to 21 days post-vaccination (i.e. Day 3 - Day 22)
  measure: To assess frequency and severity of any late onset adverse event of special interest (AESI) during the entire study
  time frame: starting 22 days post-vaccination (i.e. Day 23 - Day 180)
  measure: To assess CHIKV viremia
  time frame: on Days 1, 4, 8 and 15 (Day 29 and Day 57, if applicable)
  measure: To assess HIV viral load
  time frame: on Days 1, 15, 29, 57, 85, and 180
  measure: Immune response as measured by CHIKV-specific neutralizing antibody titers post-vaccination as determined by μPRNT assay
  time frame: Day 15, Day 29, Day 57, Day 85 and Day 180
  measure: Proportion of participants with seroresponse levels post-vaccination as determined by μPRNT assay
  time frame: Day 15, Day 29, Day 57, Day 85 and Day 180
  measure: Proportion of participants with seroconversion as compared to baseline as determined by μPRNT assay
  time frame: Day 29 and Day 180
  measure: Fold increase of CHIKV-specific neutralizing antibody titers determined by μPRNT assay post-vaccination as compared to baseline
  time frame: Day 15, Day 29, Day 57, Day 85 and Day 180
  measure: Proportion of participants reaching an at least 4-fold, 8-fold, 16-fold or 64-fold increase in CHIKV-specific neutralizing antibody titer compared to baseline as measured by μPRNT assay
  time frame: Day 15, Day 29, Day 57, Day 85 and Day 180
  arm group label: VLA1553
  arm group type: Experimental
  intervention type: Biological
  intervention name: VLA1553
  description: Single intramuscular vaccination on Day 1 with VLA1553, a lyophilized live-attenuated Chikungunya vaccine candidate 1x10E4 TCID50 per dose
  arm group label: VLA1553
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Valneva Clinical Development
  role: Study Chair
  affiliation: Valneva Austria GmbH
  last name: Valneva Clinical Development
  phone: +43 1 206 20
  phone ext: 0
  email: office@valneva.com
  responsible party type: Sponsor
  mesh term: Acquired Immunodeficiency Syndrome
  mesh term: HIV Infections
  mesh term: Chikungunya Fever
  sharing ipd: Undecided