Clinical Trial: Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-4995) in Healthy Adults

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

Official Title: Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-4995, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4

Brief Summary: Dengue fever, which is caused by dengue viruses, is a major health problem in tropical and subtropical regions of the world. The purpose of this study is to evaluate the safety and immune response to the dengue vaccine DEN4delta30-4995 in healthy adults.

Detailed Summary:

Dengue viruses account for more than 50 million cases of dengue fever and a half million cases of the more severe disease, dengue hemorrhagic fever/dengue shock syndrome. Infection with dengue viruses is the leading cause of hospitalization and death in children in at least eight Asian countries. The goal of producing a vaccine against dengue fever is to induce a long-lived antibody response against all four dengue serotypes. The rDEN4delta30-4995 vaccine candidate is a live attenuated recombinant virus derived from rDEN4delta30 for protection against dengue virus serotype 4. The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of rDEN4delta30-4995 in healthy adults.

This study will last 180 days (6 months). Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30 or placebo at study entry. Participants in Cohort 2 will be randomly assigned to receive a lower dose of rDEN4delta30 or placebo. Participants in Cohort 3 will be randomly assigned to receive the lowest dose of rDEN4delta30 or placebo. Cohorts 2 and 3 will begin after a safety review of all participants in the previous cohort.

After initial vaccination, participants in Cohort 1 will be followed every other day for the first 16 days of the study, monitoring their temperature three times a day through Day 16 and recording these measurements in a diary. After Day 16, study visits will occur on Days 21, 28, 42, and 180 and will include a physical exam and blood collection. Some participants will also be asked to undergo a skin biopsy or additional blood collection at selected visits.


Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Frequency of vaccine-related adverse events, graded by severity for each dose [ Time Frame: Throughout study ]
  • Immunogenicity of the rDEN4delta30-4995 vaccine against DEN4 virus by measurement of plaque reduction neutralization titers (PRNT) [ Time Frame: At Days 28 and 42 ]


Original Primary Outcome:

  • Frequency of vaccine-related adverse events, graded by severity for each dose
  • immunogenicity of the rDEN4delta30-4995 vaccine against DEN4 virus by measurement of plaque reduction neutralization titers (PRNT) at Days 28 and 42


Current Secondary Outcome:

  • Durability of antibody responses to DEN4 virus [ Time Frame: At Month 6 ]
  • Frequency, quantity, and duration of viremia in each dose cohort studied based on the mean peak viremia, mean day onset of viremia, and mean duration of viremia of each dose cohort [ Time Frame: Throughout study ]
  • Number of vaccinees infected with the rDEN4delta30-4995 chimeric vaccine [ Time Frame: Throughout study ]


Original Secondary Outcome:

  • Durability of antibody responses to DEN4 virus at Month 6
  • Frequency, quantity, and duration of viremia in each dose cohort studied based on the mean peak viremia, mean day onset of viremia, and mean duration of viremia of each dose cohort
  • Number of vaccinees infected with the rDEN4delta30-4995 chimeric vaccine


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

Dates:
Date Received: May 4, 2006
Date Started: January 2007
Date Completion:
Last Updated: August 5, 2009
Last Verified: November 2008