The purpose of this study is to evaluate the safety of and immune response to two doses of a dengue vaccine (TV003) given 6 months apart to healthy adults, adolescents, and children in Thailand.
Dengue infection is a leading cause of illness and death in the tropics and subtropics. The infection is caused by any one of four types of the dengue virus. This study will evaluate the safety of and immunogenicity to a vaccine (called TV003) against all four types of the dengue virus in healthy adults, adolescents, and children aged 12 months to 50 years in Thailand. Participants will be enrolled sequentially in four age groups (adults, adolescents, children, and young children), and researchers will evaluate safety data before enrolling each subsequent cohort. Each participant will be in the study for approximately 12 months. At study entry (Day 0), participants will be randomly assigned to receive either the TV003 vaccine or a placebo vaccine for TV003. All participants will receive two doses of TV003 or placebo-the first dose at study entry (Day 0) and the second dose 6 months later on Day 180. Additional study visits will occur on Days 6, 9, 12, 15, 28, 56, 72, 186, 189, 192, 195, 208, 236, 252, and 360. All study visits will include a medical history review and a physical exam. Select study visits will also include blood collection and a urine pregnancy test for participants of childbearing potential. At the vaccination study visits, participants will remain in the clinic for approximately 30 minutes after each vaccination for observation and monitoring. For 20 days after each vaccination, participants will take their temperatures and record any symptoms. Throughout the entire study period, study researchers will monitor participants for suspected dengue infection.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
266
10\^3 plaque forming units (PFU) of rDEN1 delta 30, 10\^3 PFU of rDEN2/4 delta 30(ME), 10\^3 PFU of rDEN3 delta 30/31-7164, and 10\^3 PFU of rDEN4 delta 30 to be administered as 0.5 mL by subcutaneous injection in the deltoid region of the upper arm or the thigh in pediatric participants
To be administered as 0.5 mL by subcutaneous injection in the deltoid region of the upper arm or the thigh in pediatric participants
Phramongkutklao Hospital
Bangkok, Thailand
Occurrence of solicited local and general adverse events (AEs) within the 21-day (Days 0-20) follow-up period after each vaccine dose
AEs will be summarized by severity and relationship to vaccine by individuals and each group.
Time frame: Measured through Day 200
Occurrence of unsolicited AEs within the 21-day (Days 0-20) follow-up period after each vaccine dose
AEs will be summarized by severity and relationship to vaccine by individuals and each group.
Time frame: Measured through Day 200
Occurrence of serious adverse events (SAEs) throughout the entire study period
Time frame: Measured through Day 360
Serum plaque reduction neutralization titer 50% (PRNT50) to DENV-1, DENV-2, DENV-3, and DENV-4 viruses for each participant at baseline (Day 0) and Study Days 28, 56, 72, and 180 following each vaccination
Monovalent, bivalent, trivalent, and tetravalent seropositivity and seroconversion rates will be determined at these time points. Seroconversion will be defined as a 4-fold or greater rise in DENV-1, DENV-2, DENV-3, or DENV-4 neutralizing antibody titers by Day 72 compared with the pre-vaccination titer.
Time frame: Measured through Day 360
Frequency of viremia of each monovalent component of the vaccine after the first and second doses of vaccine
The mean peak of viremia, mean day of onset of viremia, and mean duration of viremia of each monovalent component within each age cohort will be calculated.
Time frame: Measured through Day 360
Quantity of viremia of each monovalent component of the vaccine after the first and second doses of vaccine
The mean peak of viremia, mean day of onset of viremia, and mean duration of viremia of each monovalent component within each age cohort will be calculated.
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Time frame: Measured through Day 360
Duration of viremia of each monovalent component of the vaccine after the first and second doses of vaccine
The mean peak of viremia, mean day of onset of viremia, and mean duration of viremia of each monovalent component within each age cohort will be calculated.
Time frame: Measured through Day 360
Number of vaccinees infected with DENV-1, DENV-2, DENV-3, and DENV-4
Defined by recovery of vaccine virus from the blood or serum of a participant and/or seropositivity OR seroconversion to DENV
Time frame: Measured through Day 360
Duration of the antibody response in recipients of the tetravalent vaccine
The PRNT50 to DENV-1, DENV-2, DENV-3, and DENV-4 will be determined for all specimens collected on Study Day 180 following each vaccination.
Time frame: Measured through Day 360