Evaluation of the Safety and the Ability of a DNA Vaccine to Protect Against Dengue Disease (TVDV)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Vical
Walter Reed Army Institute of Research (WRAIR)
Naval Medical Research Center
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01502358
First received: December 15, 2011
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Dengue Disease
Dengue Fever
Biological: Tetravalent Dengue Vaccine (TVDV)
Biological: Tetravalent Dengue Vaccine (TVDV) with Vaxfectin® (low-dose)
Biological: Tetravalent Dengue Vaccine TVDV with Vaxfectin® (High Dose)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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®

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Number of participants with adverse events (AEs) or serious adverse events (SAEs) [ Time Frame: Up to Day 360 ] [ Designated as safety issue: Yes ]
    All AEs and SAEs will be recorded during the entire duration of the study, or up to 360 days.


Secondary Outcome Measures:
  • Percent of subjects (in each group) achieving tetravalent ELISA IgM seroconversion [ Time Frame: Days 0-360 ] [ Designated as safety issue: No ]
    From date of first vaccine dose until seroconversion is achieved, up to 360 days.

  • Percent of subjects (in each group) achieving tetravalent seroconversion, by dengue plaque reduction MN50 titer [ Time Frame: Days 0-360 ] [ Designated as safety issue: No ]
    From date of first vaccine dose until seroconversion is achieved, up to 360 days.

  • MN50 titer 1 month (Study Day 120) and Study Days 180 and 270 after vaccine regimen is complete [ Time Frame: Following completion of study days 120 and 180 and 270 days after vaccine regimen is complete ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: December 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tetravalent Dengue Vaccine (TVDV)
low dose (no adjuvant)
Biological: Tetravalent Dengue Vaccine (TVDV)
Low dose delivered intramuscularly on Study Days 0, 30 and 90
Experimental: Tetravalent Dengue Vaccine (TVDV) with Vaxfectin® (low-dose)
low dose (with adjuvant)
Biological: Tetravalent Dengue Vaccine (TVDV) with Vaxfectin® (low-dose)
Low dose: TVDV formulated with Vaxfectin®; 1.0 mL volume delivered intramuscularly on Study Days 0, 30 and 90
Experimental: Tetravalent dengue Vaccine (TVDV) with Vaxfectin® (high-dose)
high dose (with adjuvant)
Biological: Tetravalent Dengue Vaccine TVDV with Vaxfectin® (High Dose)
High dose: TVDV formulated with Vaxfectin®; 1.0 mL volume delivered intramuscularly on Study Days 0, 30 and 90

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01502358

Locations
United States, Maryland
Walter Reed Army Institute of Research and Clinical Trial Center (WRAIR CTC)
Silver Spring, Maryland, United States, 20702
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Vical
Walter Reed Army Institute of Research (WRAIR)
Naval Medical Research Center
Investigators
Principal Investigator: Janine R Danko, MD Naval Medical Research Center
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01502358     History of Changes
Other Study ID Numbers: S-11-0007, WRAIR #1839, NMRC 2011.0012
Study First Received: December 15, 2011
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
dengue
dengue fever
dengue disease
tetravalent dengue vaccine
Vaxfectin®

Additional relevant MeSH terms:
Dengue
Dengue Hemorrhagic Fever
Fever
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Body Temperature Changes
Signs and Symptoms

ClinicalTrials.gov processed this record on July 24, 2014