Clinical trial NCT01502358: Evaluation of the Safety and the Ability of a DNA Vaccine to Protect Against Dengue Disease
Official title: 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®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dengue Disease
Dengue Fever
Keywords: dengue
dengue fever
dengue disease
tetravalent dengue vaccine
Vaxfectin®
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: Vical
name: Walter Reed Army Institute of Research (WRAIR)
name: Naval Medical Research Center
First posted: 2011-12-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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
* Have a positive screen for hepatitis B surface antigen (HBsAg), hepatitis C antibody, or HIV antibody
* Are pregnant or breastfeeding
* Have donated or received blood, blood products, or plasma within 30 days prior to Day 0
* Have any acute illness, including an oral body temperature \>100.4°F, within 7 days before the initial injection on Day 0
* Have a past or current history of malignant disease except for adequately treated skin cancer
* Exclusions include but are not limited to conditions pertaining to or evidence of immunodeficiency; allergies requiring treatment with antigen injections; autoimmune disease; severe migraine headaches; unstable asthma; clinically significant cardiac arrhythmias, diabetes mellitus, thyroid disease, a bleeding disorder or a seizure disorder.
* Have participated in an investigational drug, vaccine, or device study within a period of 30 days prior to Day 0;
* History of splenectomy
* Planned travel to dengue endemic areas during the study period

Primary outcomes:
measure: Number of participants with adverse events (AEs) or serious adverse events (SAEs)
timeFrame: Up to Day 360
Secondary outcomes:
measure: Percent of subjects (in each group) achieving tetravalent ELISA IgM seroconversion
timeFrame: Days 0-360
measure: Percent of subjects (in each group) achieving tetravalent seroconversion, by dengue plaque reduction MN50 titer
timeFrame: Days 0-360
measure: MN50 titer 1 month (Study Day 120) and Study Days 180 and 270 after vaccine regimen is complete
timeFrame: Following completion of study days 120 and 180 and 270 days after vaccine regimen is complete
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: Walter Reed Army Institute of Research and Clinical Trial Center (WRAIR CTC)
state: Maryland
Study officials:
affiliation: Naval Medical Research Center
name: Janine R Danko, MD
role: PRINCIPAL_INVESTIGATOR
References: