<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/NCT02239614</url>
  </required_header>
  <id_info>
    <org_study_id>S-13-10</org_study_id>
    <secondary_id>ADVP-003</secondary_id>
    <secondary_id>WRAIR #2136</secondary_id>
    <nct_id>NCT02239614</nct_id>
  </id_info>
  <brief_title>TDENV PIV and LAV Dengue Prime-boost Strategy</brief_title>
  <official_title>A Phase 1, Randomized, Open-label, Single-center, Study of TDENV-PIV and LAV Dengue Vaccine Platforms as Part of a Heterologous Prime-boost Strategy in Healthy Adults in a Nonendemic Region</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>U.S. Army Medical Research and Development Command</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>U.S. Army Medical Research and Development Command</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The potential synergistic effect of administering 2 dengue vaccine candidates that were&#xD;
      previously shown to be safe and immunogenic in humans will be evaluated in this study. A&#xD;
      prime-boost study of tetravalent dengue virus purified inactivated vaccine (TDENV-PIV) with&#xD;
      alum and tetravalent dengue live attenuated virus (TDENV-LAV) vaccine Formulation 17 (F17)&#xD;
      will gather data to help better understand the human immune response to dengue vaccination&#xD;
      and infection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">February 17, 2017</completion_date>
  <primary_completion_date type="Actual">February 17, 2016</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of solicited adverse events</measure>
    <time_frame>21 days after each vaccination</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of unsolicited adverse events</measure>
    <time_frame>28 days after each vaccination</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of hematological and biochemistry abnormalities</measure>
    <time_frame>7 and 28 days and each vaccination</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of serious adverse events</measure>
    <time_frame>Day 208 or day 360</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of potential immune-mediated diseases</measure>
    <time_frame>Day 208 or day 360</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of medically attended adverse events</measure>
    <time_frame>Day 208 or day 360</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Microneutralizing (MN) dengue antibody titers</measure>
    <time_frame>Up to 1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Dengue</condition>
  <arm_group>
    <arm_group_label>Group 1: LAV (T=0), PIV (T=28)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 0 of the study.&#xD;
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 28 of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: PIV (T=0), LAV (T=28)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 0 of the study.&#xD;
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 28 of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3: LAV (T=0), PIV (T=180)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 0 of the study.&#xD;
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 180 of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4: PIV (T=0), LAV (T=180)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 0 of the study.&#xD;
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 180 of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TDENV-LAV</intervention_name>
    <description>0.5 mL of the post-transfection LAV F17 vaccine</description>
    <arm_group_label>Group 1: LAV (T=0), PIV (T=28)</arm_group_label>
    <arm_group_label>Group 2: PIV (T=0), LAV (T=28)</arm_group_label>
    <arm_group_label>Group 3: LAV (T=0), PIV (T=180)</arm_group_label>
    <arm_group_label>Group 4: PIV (T=0), LAV (T=180)</arm_group_label>
    <other_name>TDENV-LAV F17</other_name>
    <other_name>Tetravalent dengue live attenuated virus formulation 17</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TDENV-PIV 4 µg + alum adjuvant</intervention_name>
    <description>0.5 mL of DENV serotypes 1-4 (4 µg / serotype) in alum adjuvant</description>
    <arm_group_label>Group 1: LAV (T=0), PIV (T=28)</arm_group_label>
    <arm_group_label>Group 2: PIV (T=0), LAV (T=28)</arm_group_label>
    <arm_group_label>Group 3: LAV (T=0), PIV (T=180)</arm_group_label>
    <arm_group_label>Group 4: PIV (T=0), LAV (T=180)</arm_group_label>
    <other_name>Tetravalent dengue virus purified inactivated vaccine with alum adjuvant</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female between 18 and 49 years of age (inclusive) at the time of consent&#xD;
&#xD;
          2. Able to provide written informed consent&#xD;
&#xD;
          3. Healthy as established by medical history and clinical examination before entering&#xD;
             into the study&#xD;
&#xD;
          4. Able and willing to comply with the requirements of the protocol (eg, document events&#xD;
             in memory aid, return for follow-up visits, etc.)&#xD;
&#xD;
          5. Female subject of non-childbearing potential (non-childbearing potential is defined as&#xD;
             having either a current tubal ligation at least 3 months prior to enrollment or a&#xD;
             history of a hysterectomy, ovariectomy, or is post-menopause)&#xD;
&#xD;
          6. Female subject is not breastfeeding and agrees not to breastfeed for 3 months after&#xD;
             last vaccination&#xD;
&#xD;
          7. Female subject of childbearing potential may be enrolled in the study, if the subject&#xD;
             has:&#xD;
&#xD;
               1. Practiced adequate contraception for 30 days prior to vaccinations, and&#xD;
&#xD;
               2. A negative urine pregnancy test on each day of vaccination, and&#xD;
&#xD;
               3. Agreed to continue adequate contraception until 3 months after completion of the&#xD;
                  vaccination series.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of any investigational or non-registered product (drug or vaccine) other than the&#xD;
             study vaccines during the period starting 30 days preceding the first dose of study&#xD;
             vaccine and/or planned use during the study period&#xD;
&#xD;
          2. Chronic administration (defined as more than 14 days in total) of immunosuppressants&#xD;
             or other immune-modifying drugs during the period starting 180 days prior to the first&#xD;
             vaccine dose&#xD;
&#xD;
               1. For corticosteroids, this will mean prednisone ≥ 20 mg/d or equivalent&#xD;
&#xD;
               2. Inhaled and topical steroids are allowed&#xD;
&#xD;
          3. Planned administration or administration of a vaccine/product not foreseen by the&#xD;
             study protocol during the period starting 14 days before or after each scheduled dose&#xD;
             of an investigational product&#xD;
&#xD;
          4. Planned administration of any flavivirus vaccine for the entire study duration&#xD;
&#xD;
          5. Concurrently participating in another clinical study, at any time during the study&#xD;
             period, in which the subject has been or will be exposed to an investigational or a&#xD;
             non-investigational product (pharmaceutical product or device)&#xD;
&#xD;
          6. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on&#xD;
             medical history and physical examination (no laboratory testing required)&#xD;
&#xD;
          7. Family history of congenital or hereditary immunodeficiency&#xD;
&#xD;
          8. History of, or current, auto-immune disease&#xD;
&#xD;
          9. History of any reaction or hypersensitivity likely to be exacerbated by any component&#xD;
             of the vaccine or related to a study procedure&#xD;
&#xD;
         10. Major congenital defects or serious chronic illness&#xD;
&#xD;
         11. History of any neurological disorders or seizures. (except for a childhood febrile&#xD;
             seizures)&#xD;
&#xD;
         12. Acute disease and/or fever (oral body temperature ≥ 100.4°F/38.0°C) at the time of&#xD;
             enrollment (a subject with a minor illness, ie, mild diarrhea, mild upper respiratory&#xD;
             infection, etc, without fever, may be enrolled at the discretion of the investigator)&#xD;
&#xD;
         13. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal&#xD;
             functional abnormality, as determined by physical examination or laboratory screening&#xD;
             tests&#xD;
&#xD;
         14. Administration of immunoglobulins and/or any blood products during the period starting&#xD;
             90 days preceding the first dose of study vaccine or planned administration during the&#xD;
             study period&#xD;
&#xD;
         15. History of chronic alcohol and/or drug abuse&#xD;
&#xD;
         16. Pregnant or breastfeeding female or female planning to become pregnant or planning to&#xD;
             discontinue contraceptive precautions&#xD;
&#xD;
         17. A planned move to a location that will prohibit participating in the trial prior to&#xD;
             the study end for the participant&#xD;
&#xD;
         18. Subject seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus&#xD;
             antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)&#xD;
&#xD;
         19. Safety laboratory test results that are outside the acceptable values at screening:&#xD;
&#xD;
               1. &gt; 110% upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate&#xD;
                  aminotransferase (AST), alkaline phosphatase, creatinine, serum urea nitrogen&#xD;
                  (SUN) and bilirubin (total and direct)&#xD;
&#xD;
               2. &lt; 100% lower limit of normal (LLN) or &gt; 120% ULN for hemoglobin, hematocrit and&#xD;
                  platelet count&#xD;
&#xD;
               3. &lt; 75% LLN or &gt;110% ULN for total white blood cell count (WBC)&#xD;
&#xD;
         20. Any other condition which, in the opinion of the investigator, prevents the subject&#xD;
             from participating in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MAJ Leyi Lin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Walter Reed Army Institute of Research (WRAIR)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Trials Center, Walter Reed Army Institute of Research (CTC, WRAIR)</name>
      <address>
        <city>Silver Spring</city>
        <state>Maryland</state>
        <zip>20910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>September 10, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>August 14, 2018</last_update_submitted>
  <last_update_submitted_qc>August 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>dengue fever</keyword>
  <keyword>dengue</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dengue</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aluminum Hydroxide</mesh_term>
    <mesh_term>Aluminum sulfate</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02239614
org study id: S-13-10
secondary id: ADVP-003
secondary id: WRAIR #2136
nct id: NCT02239614
lead sponsor: 
has dmc: No
The potential synergistic effect of administering 2 dengue vaccine candidates that were
      previously shown to be safe and immunogenic in humans will be evaluated in this study. A
      prime-boost study of tetravalent dengue virus purified inactivated vaccine (TDENV-PIV) with
      alum and tetravalent dengue live attenuated virus (TDENV-LAV) vaccine Formulation 17 (F17)
      will gather data to help better understand the human immune response to dengue vaccination
      and infection.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Number of solicited adverse events
time frame: 21 days after each vaccination
measure: Number of unsolicited adverse events
time frame: 28 days after each vaccination
measure: Number of hematological and biochemistry abnormalities
time frame: 7 and 28 days and each vaccination
measure: Number of serious adverse events
time frame: Day 208 or day 360
measure: Number of potential immune-mediated diseases
time frame: Day 208 or day 360
measure: Number of medically attended adverse events
time frame: Day 208 or day 360
measure: Microneutralizing (MN) dengue antibody titers
time frame: Up to 1 year
arm group label: Group 1: LAV (T=0), PIV (T=28)
arm group type: Experimental
description: Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 0 of the study.
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 28 of the study.
arm group label: Group 2: PIV (T=0), LAV (T=28)
arm group type: Experimental
description: Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 0 of the study.
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 28 of the study.
arm group label: Group 3: LAV (T=0), PIV (T=180)
arm group type: Experimental
description: Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 0 of the study.
Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 180 of the study.
arm group label: Group 4: PIV (T=0), LAV (T=180)
arm group type: Experimental
description: Tetravalent dengue purified inactivated vaccine 4 μg/serotype with alum adjuvant (TDENV-PIV 4 µg + alum adjuvant) administered intramuscularly on day 0 of the study.
Tetravalent live-attenuated dengue virus vaccine formulation 17 (TDENV-LAV) reconstituted with 0.7 mL of water-for-injection; administered subcutaneously on day 180 of the study.
intervention type: Biological
intervention name: TDENV-LAV
description: 0.5 mL of the post-transfection LAV F17 vaccine
arm group label: Group 1: LAV (T=0), PIV (T=28)
arm group label: Group 2: PIV (T=0), LAV (T=28)
arm group label: Group 3: LAV (T=0), PIV (T=180)
arm group label: Group 4: PIV (T=0), LAV (T=180)
other name: TDENV-LAV F17
other name: Tetravalent dengue live attenuated virus formulation 17
intervention type: Biological
intervention name: TDENV-PIV 4 µg + alum adjuvant
description: 0.5 mL of DENV serotypes 1-4 (4 µg / serotype) in alum adjuvant
arm group label: Group 1: LAV (T=0), PIV (T=28)
arm group label: Group 2: PIV (T=0), LAV (T=28)
arm group label: Group 3: LAV (T=0), PIV (T=180)
arm group label: Group 4: PIV (T=0), LAV (T=180)
other name: Tetravalent dengue virus purified inactivated vaccine with alum adjuvant
criteria: 
gender: All
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
last name: MAJ Leyi Lin, MD
role: Principal Investigator
affiliation: Walter Reed Army Institute of Research (WRAIR)
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dengue
mesh term: Aluminum Hydroxide
mesh term: Aluminum sulfate