A Phase 1 Study To Evaluate The Safety, Tolerability, and Immunogenicity of a Tetravalent Dengue (Serotype 1, 2, 3, and 4) Plasmid DNA Vaccine (TVDV) Formulated With and Without Vaxfectin®
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Dengue Disease
- Sponsor
- U.S. Army Medical Research and Development Command
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Number of participants with adverse events (AEs) or serious adverse events (SAEs)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The purpose of this study is to determine whether a new investigational dengue vaccine is safe, well-tolerated, and to see if an immune response against dengue disease will be generated.
Detailed Description
Arguably the need for a tetravalent dengue vaccine that will effectively induce immunity against all four dengue serotypes has never been greater. Currently, several different approaches are being taken to develop a protective tetravalent dengue vaccine. These include live-attenuated vaccines derived by serial passage in tissue culture, live chimeric vaccines, recombinant protein vaccines and DNA vaccines. While live attenuated and live chimeric vaccines have shown promise in clinical trials, viral competition with suspected immune interference resulting in imbalanced immune responses and reactogenicity with the occurrence of dengue like symptoms remains a concern. It is imperative that any candidate vaccine produce solid immunity against each of the four dengue virus serotypes. Failure to do so may place the recipient of the vaccine at risk for developing severe dengue disease (dengue hemorrhagic fever/dengue shock syndrome) following exposure to the virus serotype to which there was incomplete protective immunity, resulting in antibody dependent enhancement due to the presence of non-neutralizing anti-dengue antibodies.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female age 18 to 50 (inclusive) years old at the time of enrollment
- •Have negative anti-dengue, Japanese encephalitis, West Nile, and yellow fever ELISA serological tests
- •Be informed of the nature of the study and provide written informed consent
- •If the subject is of child-producing potential, he/she agrees to practice adequate birth control or abstain from sex
- •Have access to the WRAIR Clinical Trials for at least 270 days, and be willing to refrain from participation in other investigational clinical trials
- •Be in good general health
- •Exclusion Criteria-Subjects meeting any of the following criteria will be excluded from the study:
- •History of Flavivirus infection or history of Flavivirus vaccine (experimental or licensed product) including Japanese encephalitis, yellow fever, and dengue
- •Have a known or suspected hypersensitivity or adverse reaction to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain
- •Have received a live-attenuated vaccine within 42 days prior to the initial injection on Day 0 or a subunit or killed vaccine within 30 days of the initial injection on Day 0
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Number of participants with adverse events (AEs) or serious adverse events (SAEs)
Time Frame: Up to Day 360
All AEs and SAEs will be recorded during the entire duration of the study, or up to 360 days.
Secondary Outcomes
- Percent of subjects (in each group) achieving tetravalent ELISA IgM seroconversion(Days 0-360)
- Percent of subjects (in each group) achieving tetravalent seroconversion, by dengue plaque reduction MN50 titer(Days 0-360)
- MN50 titer 1 month (Study Day 120) and Study Days 180 and 270 after vaccine regimen is complete(Following completion of study days 120 and 180 and 270 days after vaccine regimen is complete)