Evaluating the Safety and Immune Response to Two Doses of a Dengue Virus Vaccine Administered 12 Months Apart
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Phase 1 Evaluation of the Safety and Immunogenicity of a Booster Dose of TV003 Administered 12 Months After Initial Vaccination With TV003|
- Frequency of vaccine-related adverse events (AEs), graded by severity [ Time Frame: Measured through Day 540 ] [ Designated as safety issue: Yes ]
- Measurement of neutralizing antibody titers to DEN1, DEN2, DEN3, and DEN4 at Day 0 and 28, 56, and 90 days after each vaccination [ Time Frame: Measured at Day 0 and 28, 56, and 90 days after each vaccination ] [ Designated as safety issue: No ]Monovalent, bivalent, trivalent, and tetravalent seropositivity and seroconversion rates will be determined at Day 0 and 28, 56, and 90 days after each vaccination.
- Determination if a second dose of vaccine given at Day 360 will induce seropositivity in those vaccinees who remained seronegative to one or more DENV serotypes following the first vaccination [ Time Frame: Measured through Day 540 ] [ Designated as safety issue: No ]
- Frequency, quantity, and duration of viremia following each vaccination [ Time Frame: Measured through Day 540 ] [ Designated as safety issue: No ]
- Number of vaccinees infected with DEN1, DEN2, DEN3, and DEN4 [ Time Frame: Measured through Day 540 ] [ Designated as safety issue: No ]
Infection is defined as recovery of vaccine virus from the blood or serum of a participant and/or by seropositivity to DEN virus (PRNT50 greater than or equal to 1:10).
• Seropositivity will be defined as: PRNT50 to DEN1, DEN2, DEN3, DEN4 greater than or equal to 1:10 by Day 90 post-each vaccination
- Duration of the antibody response in recipients of the tetravalent vaccine [ Time Frame: Measured through Day 540 ] [ Designated as safety issue: No ]The PRNT50 to DEN1, DEN2, DEN3, and DEN4 will be determined for all specimens collected at Day 180 post-each vaccination.
- Greater than or equal to 4-fold rise in serum neutralizing antibody titer by Day 450 compared with Day 360 [ Time Frame: Measured at Day 450 ] [ Designated as safety issue: No ]
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||June 2016|
|Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: TV003 Vaccine
Participants will receive an injection of the TV003 vaccine at study entry and Day 360.
Biological: TV003 Vaccine
TV003 will contain an admixture of the following monovalent dengue vaccines: 10^3 PFU of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30(ME), 10^3 PFU of rDEN3Δ30/31-7164, and 10^3 PFU of rDEN4Δ30. TV003 vaccine will be administered by subcutaneous injection in participants' deltoid region of the upper arm.
Placebo Comparator: Placebo Vaccine
Participants will receive an injection of the placebo vaccine at study entry and Day 360.
Biological: Placebo Vaccine
Placebo vaccine will be administered by subcutaneous injection in participants' deltoid region of the upper arm.
Dengue viruses are a major health concern, particularly in the tropical and subtropical regions of the world. The World Health Organization (WHO) has made the development of a dengue vaccine a top priority. There are four types of dengue viruses (DEN1, DEN2, DEN3, and DEN4), each of which can cause various illnesses, including dengue fever, or the more severe disease, dengue hemorrhagic fever/shock syndrome (DHF/DSS). This study will evaluate the safety and immune response to two doses of a dengue virus vaccine (TV003) when administered 12 months apart in healthy adults. The study will also evaluate whether the candidate vaccine may protect against all four types of dengue viruses.
Participants will be randomly assigned to receive the TV003 study vaccine or placebo vaccine. At study entry, participants will undergo a blood collection and physical examination, and female participants will take a pregnancy test. Participants will then receive an injection of their assigned vaccine. They will take their temperature three times a day for 16 days after each vaccination and record the results on a diary card, which research staff will review during participants' study visits. Additional study visits will occur on Days 3, 10, 14, 21, 28, 56, 90, 180, 270, and 330. All study visits will include blood collection and a physical examination; select visits will include a pregnancy test for female participants. At a study visit on Day 360, all participants will receive an injection of the same vaccine they received at study entry. Additional study visits will occur on Days 363, 370, 374, 381, 388, 416, 450, and 540, and will include the same study procedures as previously performed.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01782300
|United States, Maryland|
|Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health|
|Baltimore, Maryland, United States, 21205|
|United States, Vermont|
|University of Vermont Vaccine Testing Center|
|Burlington, Vermont, United States, 05405|
|Principal Investigator:||Anna Durbin, MD||Center for Immunization Research (CIR), Johns Hopkins School of Public Health|