Clinical Trial: A Two-dose Primary Vaccination Study of a Tetravalent Dengue Virus Purified Inactivated Vaccine vs. Placebo in Healthy Adults (in Puerto Rico)

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Va

Brief Summary: 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.

Detailed Summary:
Sponsor: U.S. Army Medical Research and Materiel Command

Current Primary Outcome:

  • 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 ]

    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
  • 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 ]

    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 tet

      Original Primary Outcome: Same as current

      Current Secondary Outcome:

      • Safety of various TDENV-PIV formulations, from Day 0 to Month 13 (Visits 1-11) [ Time Frame: Up to month 13 ]

        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
      • 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 ]

        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
      • • 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) ]
        Occurrence of serious adverse events (SAEs) related to study procedures from Month 14 to end of study (Month 37-39)


      Original Secondary Outcome: Same as current

      Information By: U.S. Army Medical Research and Materiel Command

      Dates:
      Date Received: October 4, 2012
      Date Started: November 2012
      Date Completion: December 2019
      Last Updated: May 2, 2017
      Last Verified: May 2017