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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
100
Clinical Research Center, 1st Floor University Hospital
San Juan, Puerto Rico
Safety and reactogenicity of various TDENV-PIV formulations from Day 0 through 28 days after the second dose (Day 0 - 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
Time frame: Up to Day 56
Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations 28 days after the second dose (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 tetravalent seropositivity rates
Time frame: Day 56
Safety of various TDENV-PIV formulations, from Day 0 to Month 13 (Visits 1-11)
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
Time frame: Up 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
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
Time frame: Up to month 13
• To evaluate the safety of various TDENV-PIV formulations from Month 14 through the end of the study (Visit 15)
Occurrence of serious adverse events (SAEs) related to study procedures from Month 14 to end of study (Month 37-39)
Time frame: Up to the end of study (Month 37-39)
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