Clinical Trial: Tetravalent Chimeric Dengue Vaccine Trial

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Double-Blind Randomized, Placebo-Controlled, Phase I Dose Escalation Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healt

Brief Summary: The purpose of this study is to test the safety and immune response to a live attenuated dengue vaccine that could protect people against all 4 types of dengue virus. Live attenuated means that while this vaccine contains 4 live dengue viruses the viruses have been attenuated (weakened) so as not to cause dengue disease in people. Dengue virus is spread to people by mosquitoes and can cause sickness and even death. Seventy-two subjects between the ages of 18-45 years old will be enrolled in this research study at Saint Louis University Center for Vaccine Development. Participants will be randomly assigned to 1 of 4 groups to receive 2 doses of the study vaccine or placebo (inactive substance). Study procedures include: maintaining a diary to record temperature and side effects, physical exam, electrocardiogram (ECG) (measures the activity of the heart), and blood samples. Participants will be involved in study related procedures for about 10 months.

Detailed Summary: The purpose of this study is to evaluate the safety and immunogenicity of a tetravalent dengue vaccine administered subcutaneously or intradermally. The hypotheses being tested in this study is whether or not a tetravalent dengue vaccine may be safely administered to healthy normal individuals by intradermal (ID) or subcutaneous (SC) injection and provide measurable levels of serum neutralizing antibodies against all four dengue virus serotypes. The study is also designed to compare safety and immunogenicity between routes of administration and dose levels. The primary objective of this study is to evaluate the safety and tolerability of a two-dose regimen tetravalent dengue vaccine administered either SC or ID to healthy adult volunteers. Two dose levels will be tested in a dose-escalation format. Safety and tolerability will be measured by conducting post-vaccination safety assessments including physical examinations, injection site examinations, adverse event monitoring, hematology, blood chemistry, and urine dipstick. The secondary objective of this study is to assess the immunogenicity of the vaccine, in terms of neutralizing antibodies, against all four dengue serotypes when administered at two dose levels by two routes of administration in healthy adults. Titers of serum neutralizing antibodies will be measured at pre-vaccination, after prime and boost vaccinations and assessed by comparing titers at the two dose levels as well as the two routes of administration. In addition, viremia deriving from the attenuated vaccine viruses will be measured on days 0 (baseline), 2, 4, 5/6, 7, 9, 11, and 14 after both prime and boost vaccinations. Levels of neutralizing antibodies will also be measured in samples to be obtained on days 180 and 270 for analysis and submission in a supplement to the study report. This study will enroll 72 healthy flavivirus-negative male and female subjects between the ages of 18 and 45.
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Number of volunteers overall and in each dose group with unsolicited vaccine-associated adverse events (AEs) in each dose group. [ Time Frame: From time the first dose of vaccine is administered until the end of the study (Study Days 0-270 or through termination visit, if terminated early). ]
  • Number of volunteers overall and in each dose group with local or systemic vaccine reactogenicity, based on evaluation of solicited adverse events (AEs) recorded on subject memory aids or during clinical assessments. [ Time Frame: Through 14 days after prime or boost vaccination. ]
  • Number of volunteers overall and in each dose group with vaccine-associated serious adverse events (SAEs). [ Time Frame: From time the first dose of vaccine is administered (Day0) until the end of the study (Day 270). ]


Original Primary Outcome:

  • Number of volunteers overall and in each dose group with unsolicited vaccine-associated adverse events (AEs) in each dose group. [ Time Frame: From time the first dose of vaccine is administered until the end of the study. ]
  • Number of volunteers overall and in each dose group with vaccine-associated serious adverse events (SAEs). [ Time Frame: From time the first dose of vaccine is administered until the end of the study. ]
  • Number of volunteers overall and in each dose group with local or systemic vaccine reactogenicity, based on evaluation of solicited adverse events (AEs) recorded on subject memory aids or during clinical assessments. [ Time Frame: Through 14 days after prime or boost vaccination. ]


Current Secondary Outcome:

  • Immunogenicity: geometric mean neutralizing antibody titers (GMT) to each of the 4 dengue serotypes. [ Time Frame: At 14, 30, 60, and 90 days after the prime vaccination on Day 0, and at 14 and 30 days after the boost vaccination on Day 90. ]
  • Viremia: incidence, duration, and titer of viremia for each of the DENVax vaccine components. [ Time Frame: Days 0, 2, 4, 5/6, 7, 9, 11, and 14 after each vaccination. ]
  • Immunogenicity: durability of vaccine-induced immune responses based on neutralizing antibody titers to all 4 dengue serotypes. [ Time Frame: At 90 days and 180 days after the boost vaccination will be analyzed for inclusion in a supplemental study report. ]
  • Immunogenicity: proportion of subjects seroconverting to each of the 4 dengue serotypes, where seroconversion is defined as plaque reduction neutralization assay (PRNT)50 titer greater than or equal to 10. [ Time Frame: Days 0 (pre-prime dose), 14, 30, 60, 90 (pre-booster dose), 104 and 120. ]


Original Secondary Outcome:

  • Immunogenicity: geometric mean neutralizing antibody titers (GMT) to each of the 4 dengue serotypes. [ Time Frame: At 14, 30, 60, and 90 days after the prime vaccination on Day 0, and at 14 and 30 days after the boost vaccination on Day 90. ]
  • Immunogenicity: durability of vaccine-induced immune responses based on neutralizing antibody titers to all 4 dengue serotypes. [ Time Frame: At 90 days and 180 days after the boost vaccination will be analyzed for inclusion in a supplemental study report. ]
  • Immunogenicity: proportion of subjects seroconverting to each of the 4 dengue serotypes, where seroconversion is defined as plaque reduction neutralization assay (PRNT)50 titer greater than or equal to 10. [ Time Frame: After the prime and boost vaccinations: Days 14, 30, 60, 90 (pre-booster dose), 104 and 120. ]
  • Viremia: incidence, duration, and titer of viremia for each of the DENVax vaccine components. [ Time Frame: After the prime and boost vaccinations: Days 14, 30, 60, 90 (pre-booster dose), 104 and 120. ]


Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: April 22, 2010
Date Started: May 2010
Date Completion:
Last Updated: January 31, 2013
Last Verified: January 2013