<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/NCT01702857</url>
  </required_header>
  <id_info>
    <org_study_id>S-12-12</org_study_id>
    <secondary_id>116614</secondary_id>
    <secondary_id>WRAIR 1945</secondary_id>
    <secondary_id>DPIV-002</secondary_id>
    <nct_id>NCT01702857</nct_id>
  </id_info>
  <brief_title>A Two-dose Primary Vaccination Study of a Tetravalent Dengue Virus Purified Inactivated Vaccine vs. Placebo in Healthy Adults (in Puerto Rico)</brief_title>
  <acronym>DPIV-002</acronym>
  <official_title>A Phase I, Randomized, Placebo-Controlled, Observer-blind, Two-dose (0-28 Day Schedule) Primary Vaccination Study of WRAIR Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) in Healthy Adults in Puerto Rico</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>U.S. Army Medical Research and Development Command</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Walter Reed Army Institute of Research (WRAIR)</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>U.S. Army Medical Research and Development Command</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a first time in humans (FTiH) study designed to assess the experimental TDENV-PIV&#xD;
      vaccine in a predominantly dengue-primed adult population. The study is designed to afford a&#xD;
      first time in humans (FTiH) safety and immunogenicity assessment of three TDENV-PIV vaccine&#xD;
      candidates, each formulated with a different adjuvant: either aluminum hydroxide, AS01E or&#xD;
      AS03B (adjuvants used in GSK Biologicals' hepatitis B candidate vaccine, malaria candidate&#xD;
      vaccine and pandemic flu vaccine, respectively). Each vaccine candidate will contain 1 µg of&#xD;
      purified virus antigen per each of the four DENV types. Additionally, the study will evaluate&#xD;
      an alum adjuvanted TDENV-PIV vaccine candidate containing 4 µg of purified virus antigen per&#xD;
      each of the four DENV types. The control group will receive a saline placebo. All&#xD;
      experimental vaccinations will be administered according to a 2-dose schedule, 28 days apart.&#xD;
      There is a parallel FTiH study that is conducted in the United States in a dengue-naive&#xD;
      population using the same investigational vaccines.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2012</start_date>
  <completion_date type="Actual">March 23, 2017</completion_date>
  <primary_completion_date type="Actual">January 20, 2017</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>Safety and reactogenicity of various TDENV-PIV formulations from Day 0 through 28 days after the second dose (Day 0 - Day 56)</measure>
    <time_frame>Up to Day 56</time_frame>
    <description>Safety and Reactogenicity:&#xD;
Occurrence, intensity and relationship to vaccination of solicited local and general adverse events (AEs) during the 7-day follow-up period post each vaccination (Day 0-6)&#xD;
Occurrence, intensity and relationship to vaccination of unsolicited AEs during the 28-day follow-up period post each vaccination (Day 0-27)&#xD;
Hematological and biochemical levels at study visits on Days 0, 7, 28, 35 and 56&#xD;
Occurrence of serious adverse events (SAEs) from Day 0 to Day 56&#xD;
Occurrence of potential immune-mediated diseases (pIMDs) and medically attended AEs from Day 0 to Day 56</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations 28 days after the second dose (Day 56)</measure>
    <time_frame>Day 56</time_frame>
    <description>Humoral Immunogenicity:&#xD;
Neutralizing antibody titers specific to each DENV type at Day 56&#xD;
Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type&#xD;
Rate of fold increases in neutralizing antibody from Day 0 for each DENV type&#xD;
Seropositivity rates for each DENV type&#xD;
Trivalent and tetravalent seropositivity rates</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of various TDENV-PIV formulations, from Day 0 to Month 13 (Visits 1-11)</measure>
    <time_frame>Up to month 13</time_frame>
    <description>Safety:&#xD;
Hematological and biochemical levels at study visits on Months 4, 7, 10 and Month 13&#xD;
Occurrence of pIMDs and medically attended AEs from Day 0 to Month 13&#xD;
Occurrence of any SAE from Day 0 to Month 13</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations on Days 0, 7 and 28 and Months 7 and 13</measure>
    <time_frame>Up to month 13</time_frame>
    <description>Humoral Immunogenicity:&#xD;
Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type&#xD;
Rate of fold increases in neutralizing antibody from Day 0 for each DENV type&#xD;
Seropositivity rates for each DENV type&#xD;
Trivalent and tetravalent seropositivity rates</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• To evaluate the safety of various TDENV-PIV formulations from Month 14 through the end of the study (Visit 15)</measure>
    <time_frame>Up to the end of study (Month 37-39)</time_frame>
    <description>Occurrence of serious adverse events (SAEs) related to study procedures from Month 14 to end of study (Month 37-39)</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Dengue Fever</condition>
  <arm_group>
    <arm_group_label>TDENV-PIV alum4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 µg TDENV-PIV with Alum adjuvant; 0.5 mL intramuscular injection at 0 and 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TDENV-PIV AS03B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 µg TDENV-PIV with AS03B adjuvant; 0.5 mL intramuscular injection at 0 and 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Phosphate buffered saline; 0.5 mL intramuscular injection at 0 and 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TDENV-PIV alum1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 µg TDENV-PIV with Alum adjuvant; 0.5 mL intramuscular injection at 0 and 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TDENV-PIV AS01E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 µg TDENV-PIV with AS01E adjuvant; 0.5 mL intramuscular injection at 0 and 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Biological/Vaccine: 4 µg TDENV-PIV with Alum adjuvant</intervention_name>
    <arm_group_label>TDENV-PIV alum4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Biological/Vaccine: 1 µg TDENV-PIV with AS03B adjuvant</intervention_name>
    <arm_group_label>TDENV-PIV AS03B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Phosphate buffered saline</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>1 µg TDENV-PIV with Alum adjuvant</intervention_name>
    <arm_group_label>TDENV-PIV alum1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>1 µg TDENV-PIV with AS01E adjuvant</intervention_name>
    <arm_group_label>TDENV-PIV AS01E</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who the investigator believes can and will comply with the requirements of&#xD;
             the protocol (e.g., completion of the diary cards, return for follow-up visits, etc.)&#xD;
&#xD;
          -  A male or female between 20 and 39 years of age (inclusive) at the time of consent&#xD;
&#xD;
          -  Written informed consent obtained from the subject&#xD;
&#xD;
          -  Healthy subjects as established by medical history and clinical examination before&#xD;
             entering into the study&#xD;
&#xD;
          -  Subject has lived in the Caribbean for more than 10 years&#xD;
&#xD;
          -  Female subjects of non-childbearing potential (non-childbearing potential is defined&#xD;
             as having either a current tubal ligation at least three months prior to enrollment,&#xD;
             hysterectomy, ovariectomy, or is post-menopause).&#xD;
&#xD;
          -  Female subjects of childbearing potential may be enrolled in the study, if the subject&#xD;
             has:&#xD;
&#xD;
               -  practiced adequate contraception for 30 days prior to vaccination, and&#xD;
&#xD;
               -  a negative urine pregnancy test on the day of vaccination, and&#xD;
&#xD;
               -  agreed to continue adequate contraception until two months after completion of&#xD;
                  the vaccination series&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of any investigational or non-registered product (drug or vaccine) other than the&#xD;
             study vaccines/placebo during the period starting 30 days preceding the first dose of&#xD;
             study vaccine/placebo and/or planned use during the study period&#xD;
&#xD;
          -  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/placebo dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day or&#xD;
             equivalent; inhaled and topical steroids are allowed)&#xD;
&#xD;
          -  Planned administration or administration of a vaccine/product not foreseen by the&#xD;
             study protocol during the Exclusion:&#xD;
&#xD;
          -  Use of any investigational or non-registered product (drug or vaccine) other than the&#xD;
             study vaccines/placebo during the period starting 30 days preceding the first dose of&#xD;
             study vaccine/placebo and/or planned use during the study period&#xD;
&#xD;
          -  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/placebo dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day or&#xD;
             equivalent; inhaled and topical steroids are allowed)&#xD;
&#xD;
          -  Planned administration or administration of a vaccine/product not foreseen by the&#xD;
             study protocol during the period starting 30 days prior to the first dose of&#xD;
             vaccine/placebo until after the visit at Day 56 (if influenza activity warrants&#xD;
             vaccination of healthy young adults, influenza vaccination will be encouraged and will&#xD;
             not lead to study exclusion)&#xD;
&#xD;
          -  Previous or planned administration of any other flavivirus vaccine (approved or&#xD;
             investigational) for the entire study duration&#xD;
&#xD;
          -  Previous receipt of any investigational dengue virus vaccine&#xD;
&#xD;
          -  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;
          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on&#xD;
             medical history and physical examination (no laboratory testing required).&#xD;
&#xD;
          -  Family history of congenital or hereditary immunodeficiency&#xD;
&#xD;
          -  History of, or current auto-immune disease&#xD;
&#xD;
          -  History of any reaction or hypersensitivity likely to be exacerbated by any component&#xD;
             of the vaccine/placebo or related to a study procedure&#xD;
&#xD;
          -  Major congenital defects or serious chronic illness&#xD;
&#xD;
          -  History of any neurological disorders or seizures&#xD;
&#xD;
          -  Acute disease and/or fever (≥37.5°C/99.5°F oral body temperature) at the time of&#xD;
             enrollment (a subject with a minor illness, i.e., mild diarrhea, mild upper&#xD;
             respiratory infection, etc., without fever, may be enrolled at the discretion of the&#xD;
             investigator)&#xD;
&#xD;
          -  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;
          -  Administration of immunoglobulins and/or any blood products during the period starting&#xD;
             90 days preceding the first dose of study vaccine/placebo or planned administration&#xD;
             during the study period&#xD;
&#xD;
          -  History of chronic alcohol consumption and/or drug abuse&#xD;
&#xD;
          -  Pregnant or lactating female or female planning to become pregnant or planning to&#xD;
             discontinue contraceptive precautions&#xD;
&#xD;
          -  A planned move to a location that will prohibit participating in the trial until study&#xD;
             end for the participant&#xD;
&#xD;
          -  Any other condition which, in the opinion of the investigator, prevents the subject&#xD;
             from participating in the study.&#xD;
&#xD;
          -  Subject seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus&#xD;
             antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)&#xD;
&#xD;
          -  Safety laboratory test results that are outside the normal limits for their age,&#xD;
             gender, and locality at screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>39 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clemente Diaz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Puerto Rico</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Research Center, 1st Floor University Hospital</name>
      <address>
        <city>San Juan</city>
        <zip>00936-5067</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Puerto Rico</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <last_update_submitted>May 22, 2017</last_update_submitted>
  <last_update_submitted_qc>May 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dengue</keyword>
  <keyword>Dengue fever</keyword>
  <keyword>Dengue Hemorrhagic Fever</keyword>
  <keyword>Flavivirus</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>Vaccines</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/NCT01702857
org study id: S-12-12
secondary id: 116614
secondary id: WRAIR 1945
secondary id: DPIV-002
nct id: NCT01702857
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This is a first time in humans (FTiH) study designed to assess the experimental TDENV-PIV
      vaccine in a predominantly dengue-primed adult population. The study is designed to afford a
      first time in humans (FTiH) safety and immunogenicity assessment of three TDENV-PIV vaccine
      candidates, each formulated with a different adjuvant: either aluminum hydroxide, AS01E or
      AS03B (adjuvants used in GSK Biologicals' hepatitis B candidate vaccine, malaria candidate
      vaccine and pandemic flu vaccine, respectively). Each vaccine candidate will contain 1 µg of
      purified virus antigen per each of the four DENV types. Additionally, the study will evaluate
      an alum adjuvanted TDENV-PIV vaccine candidate containing 4 µg of purified virus antigen per
      each of the four DENV types. The control group will receive a saline placebo. All
      experimental vaccinations will be administered according to a 2-dose schedule, 28 days apart.
      There is a parallel FTiH study that is conducted in the United States in a dengue-naive
      population using the same investigational vaccines.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety and reactogenicity of various TDENV-PIV formulations from Day 0 through 28 days after the second dose (Day 0 - Day 56)
time frame: Up to Day 56
description: Safety and Reactogenicity:
Occurrence, intensity and relationship to vaccination of solicited local and general adverse events (AEs) during the 7-day follow-up period post each vaccination (Day 0-6)
Occurrence, intensity and relationship to vaccination of unsolicited AEs during the 28-day follow-up period post each vaccination (Day 0-27)
Hematological and biochemical levels at study visits on Days 0, 7, 28, 35 and 56
Occurrence of serious adverse events (SAEs) from Day 0 to Day 56
Occurrence of potential immune-mediated diseases (pIMDs) and medically attended AEs from Day 0 to Day 56
measure: Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations 28 days after the second dose (Day 56)
time frame: Day 56
description: Humoral Immunogenicity:
Neutralizing antibody titers specific to each DENV type at Day 56
Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type
Rate of fold increases in neutralizing antibody from Day 0 for each DENV type
Seropositivity rates for each DENV type
Trivalent and tetravalent seropositivity rates
measure: Safety of various TDENV-PIV formulations, from Day 0 to Month 13 (Visits 1-11)
time frame: Up to month 13
description: Safety:
Hematological and biochemical levels at study visits on Months 4, 7, 10 and Month 13
Occurrence of pIMDs and medically attended AEs from Day 0 to Month 13
Occurrence of any SAE from Day 0 to Month 13
measure: Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations on Days 0, 7 and 28 and Months 7 and 13
time frame: Up to month 13
description: Humoral Immunogenicity:
Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type
Rate of fold increases in neutralizing antibody from Day 0 for each DENV type
Seropositivity rates for each DENV type
Trivalent and tetravalent seropositivity rates
measure: • To evaluate the safety of various TDENV-PIV formulations from Month 14 through the end of the study (Visit 15)
time frame: Up to the end of study (Month 37-39)
description: Occurrence of serious adverse events (SAEs) related to study procedures from Month 14 to end of study (Month 37-39)
arm group label: TDENV-PIV alum4
arm group type: Experimental
description: 4 µg TDENV-PIV with Alum adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
arm group label: TDENV-PIV AS03B
arm group type: Experimental
description: 1 µg TDENV-PIV with AS03B adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Phosphate buffered saline; 0.5 mL intramuscular injection at 0 and 28 days
arm group label: TDENV-PIV alum1
arm group type: Experimental
description: 1 µg TDENV-PIV with Alum adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
arm group label: TDENV-PIV AS01E
arm group type: Experimental
description: 1 µg TDENV-PIV with AS01E adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
intervention type: Biological
intervention name: Biological/Vaccine: 4 µg TDENV-PIV with Alum adjuvant
arm group label: TDENV-PIV alum4
intervention type: Biological
intervention name: Biological/Vaccine: 1 µg TDENV-PIV with AS03B adjuvant
arm group label: TDENV-PIV AS03B
intervention type: Other
intervention name: Phosphate buffered saline
arm group label: Placebo
intervention type: Biological
intervention name: 1 µg TDENV-PIV with Alum adjuvant
arm group label: TDENV-PIV alum1
intervention type: Biological
intervention name: 1 µg TDENV-PIV with AS01E adjuvant
arm group label: TDENV-PIV AS01E
criteria: 
gender: All
minimum age: 20 Years
maximum age: 39 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clemente Diaz, MD
role: Principal Investigator
affiliation: University of Puerto Rico
facility: 
country: Puerto Rico
responsible party type: Sponsor
mesh term: Dengue
mesh term: Aluminum Hydroxide
mesh term: Vaccines
mesh term: Aluminum sulfate