Evaluating the Safety and Immune Response to a Dengue Virus Vaccine in Healthy Adults
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Phase 1 Evaluation of the Safety and Immunogenicity of rDEN2Δ30-7169, a Live Attenuated Monovalent Dengue Virus Vaccine|
- Safety of rDEN2Δ30-7169 vaccine as assessed by the frequency of vaccine-related adverse events (AEs) [ Time Frame: Measured through participants' last study visit at Day 180 ]AEs are classified by both severity and seriousness, through active and passive surveillance.
- Frequency, quantity, and duration of viremia following vaccination [ Time Frame: Measured through participants' last study visit at Day 180 ]Subjects will have samples assayed for vaccine virus on Study Days 0, 2, 4, 6, 8, 10, 12, 14, and 16. Serum will be serially diluted and the titer of vaccine virus determined.
- Immune response of the vaccine at 4 and 8 weeks post-vaccination [ Time Frame: Measured at 4 and 8 weeks post-vaccination ]Seropositivity to DENV-2 is defined as PRNT50 ≥ 1:10. Seroconversion is defined as a ≥ 4-fold rise in PRNT50 to wt DENV-2 Tonga/74 by Study Day 56.
- Titer of virus vaccine [ Time Frame: Measured through participants' last study visit at Day 180 ]The peak titer, day of onset, and duration of viremia will be calculated for each subject within the vaccinated group.
- Number of vaccinees who seroconvert to DENV-2 by study Day 56 [ Time Frame: Measured through Day 56 ]Seroconversion will be defined as a ≥ 4-fold rise in PRNT50 to wt DENV-2 Tonga/74 by Study Day 56.
- Number of vaccinees infected with rDEN2Δ30-7169 vaccine [ Time Frame: Measured through participants' last study visit at Day 180 ]Infection is defined as recovery of vaccine virus from the blood or serum of a subject and/or by seroconversion to DENV-2 defined as a ≥ 4-fold rise in DENV-2 neutralizing antibody titers by Study Day 56 when compared with Study Day 0.
- Comparison of infectivity rates, safety, and immunogenicity of a single dose of rDEN2Δ30 vaccine with the reported infectivity and safety of rDEN2/4Δ30 from previous clinical trials [ Time Frame: Measured through participants' last study visit at Day 180 ]
- Durability of neutralizing antibody by measuring serum neutralizing antibody to DENV-2 out to 180 days after vaccination [ Time Frame: Measured through participants' last study visit at Day 180 ]
|Study Start Date:||June 2013|
|Study Completion Date:||May 2015|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: rDEN2Δ30-7169 vaccine
Participants will receive a single injection of the rDEN2Δ30-7169 vaccine at study entry.
Biological: rDEN2Δ30-7169 vaccine
Administered at a dose of 10^3 plaque-forming units (PFU); delivered by subcutaneous injection in the deltoid region of the upper arm
Placebo Comparator: Placebo
Participants will receive a single injection of placebo at study entry.
Delivered by subcutaneous injection in the deltoid region of the upper arm
Dengue viruses can cause dengue fever and the more severe disease, dengue hemorrhagic fever/shock syndrome (DHF/DSS). Infection with dengue viruses is the leading cause of hospitalization and death in children in at least 8 tropical Asian countries. There are 4 types of dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4), each of which can cause dengue illness ranging from a mild illness to life-threatening disease. This study will evaluate the experimental rDEN2Δ30-7169 vaccine for the prevention of illness due to DENV-2. The purpose of this study is to evaluate the safety and immunogenicity of this vaccine in healthy adults with no history of previous flavivirus infection.
At study entry, participants will be randomly assigned to receive either the dengue virus vaccine or placebo. They will remain in the clinic for 30 minutes after receiving the injection for monitoring. Study visits will occur at Days 2, 4, 6, 8, 10, 12, 14, 16, 21, 28, 56, and 180. All study visits will include a blood collection, and most study visits will include a physical examination. Female participants will have a pregnancy test at select visits. Participants will record their temperature at least 3 times a day for the first 16 days; study researchers will review these readings during the study visits.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01931176
|United States, Maryland|
|John Hopkins Bloomberg School of Public Health - Center for Immunization Research (CIR)|
|Baltimore, Maryland, United States, 21205|
|Principal Investigator:||Anna Durbin, MD||Center for Immunization Research (CIR), Johns Hopkins School of Public Health|