Evaluating the Safety and Immune Response to Two Admixtures of a Tetravalent Dengue Virus Vaccine
|Dengue||Biological: TetraVax-DV Vaccine - Admixture TV003 Biological: TetraVax-DV Vaccine - Admixture TV005 Biological: Placebo||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Phase 1 Evaluation of the Safety and Immunogenicity of the Recombinant Live Attenuated Tetravalent Dengue Virus Vaccine Admixtures TV003 and TV005 in Healthy Flavivirus-experienced Adult Subjects|
- Safety of TetraVax-DV TV003 and TV005, as assessed by the frequency of vaccine-related adverse events [ Time Frame: Measured through Day 360 ]
- Immunogenicity of TV003 and TV005, as assessed by neutralizing antibody titers to DENV-1, DENV-2, DENV-3, and DENV-4 [ Time Frame: Measured 28, 56, 90, and 180 days after each vaccination ]Monovalent, bivalent, trivalent, and tetravalent seropositivity rates will be determined at 28, 56, and 90 days after each vaccination.
- Whether a second dose of the vaccine given at Day 180 will induce seropositivity in those participants that remained seronegative to one or more DENV serotypes following the first vaccination [ Time Frame: Measured through Day 360 ]
- Frequency, quantity, and duration of viremia following vaccination [ Time Frame: Measured through Day 360 ]
- Number of flavivirus-experienced vaccinees infected with DENV-1, DENV-2, DENV-3, and DENV-4 [ Time Frame: Measured through Day 360 ]Infection is defined as recovery of vaccine virus from the blood or serum of a participant and/or by developing seropositivity to DEN virus (plaque reduction neutralization titer [PRNT]50 greater than or equal to 1:10).
- Duration of the neutralizing antibody response [ Time Frame: Measured 26 weeks after each vaccination ]
|Study Start Date:||December 2011|
|Study Completion Date:||September 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: TetraVax-DV Vaccine - Admixture TV003
Participants will receive one SC injection of the TetraVax-DV Vaccine - Admixture TV003 in their upper arm at Day 0 and Day 180.
Biological: TetraVax-DV Vaccine - Admixture TV003
One SC injection at Day 0 and Day 180 of the TetraVax-DV Vaccine, Admixture TV003 (10^3 plaque-forming unit [PFU] of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3Δ30/31-7164, and 10^3 PFU of rDEN4Δ30)
Experimental: TetraVax-DV Vaccine - Admixture TV005
Participants will receive one SC injection of the TetraVax-DV Vaccine - Admixture TV005 in their upper arm at Day 0 and Day 180.
Biological: TetraVax-DV Vaccine - Admixture TV005
One SC injection at Day 0 and Day 180 of the TetraVax-DV Vaccine, Admixture TV005 (10^3 PFU of rDEN1Δ30, 10^4 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3Δ30/31-7164, and 10^3 PFU of rDEN4Δ30)
Placebo Comparator: Placebo
Participants will receive one SC injection of placebo in their upper arm at Day 0 and Day 180.
One SC injection at Day 0 and Day 180 of placebo
Dengue viruses cause dengue fever and the more severe condition, dengue hemorrhagic fever/shock syndrome. Dengue viruses are common in most tropical and subtropical regions of the world and infection with dengue viruses is the leading cause of hospitalization and death in children in many tropical Asian countries. For these reasons, the World Health Organization (WHO) has made the development of a dengue virus vaccine a top priority. This study will evaluate the safety and immunogenicity of two doses of a live attenuated, tetravalent dengue virus vaccine called TetraVax-DV in healthy adults (18-50 years old) who have previously been infected with a dengue virus or other flavivirus or have previously received a flavivirus vaccine. Two different formulations of the TetraVax-DV vaccine will be evaluated.
Participants will be randomly assigned to receive one of two admixtures of the TetraVax-DV vaccine or a placebo. At a baseline study visit (Day 0), participants will undergo a medical history review, physical examination, blood collection, vital sign measurements, and a pregnancy test for females. Participants will then receive one subcutaneous (SC) injection of their assigned vaccine or placebo in the upper arm. After receiving the vaccine, participants will remain in the clinic for 30 minutes for observation and monitoring. At home, participants will monitor and record their temperature three times a day for 16 days after the first vaccination (from Day 0 through Day 16) and for 16 days after the second vaccination (from Day 180 through Day 196). Additional study visits will occur at Days 3, 8, 10, 12, 14, 16, 21, 28, 56, 90, and 150 and will include a physical examination, vital sign measurements, and blood collection. On Day 180, participants will receive a second SC injection of their assigned vaccine or placebo. Additional study visits will then occur at Days 183, 188, 190, 192, 194, 196, 201, 208, 236, 270, and 360, and will include the same study procedures and monitoring that occurred after the first vaccination.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01506570
|United States, Maryland|
|Center for Immunization Research, Johns Hopkins School of Public Health|
|Baltimore, Maryland, United States|
|United States, Vermont|
|Fletcher Allen Health Care (FAHC), General Clinical Research Center (GCRC)|
|Burlington, Vermont, United States|
|University of Vermont Vaccine Testing Center|
|Burlington, Vermont, United States|
|Principal Investigator:||Anna Durbin, MD||Center for Immunization Research (CIR), Johns Hopkins School of Public Health|