Clinical Trial: Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-200,201) in Healthy Adults

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

Official Title: Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-200,201, 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 test the safety of and immune response to a new dengue virus vaccine in healthy adults.

Detailed Summary:

Dengue viruses cause dengue fever and the more severe dengue hemorrhagic fever/shock syndrome. More than 2 billion people living in tropical and subtropical regions of the world are at risk of dengue virus infection, which is the leading cause of hospitalization and death in children in several tropical Asian countries. This study will evaluate the safety and immunogenicity of a live attenuated dengue virus vaccine called rDEN4delta30-200,201. This vaccine is derived from rDEN4delta30, another dengue virus vaccine candidate that has been shown to be safe and immunogenic in Phase I and II trials in healthy adults.

This study will last 180 days. There will be three cohorts in this dose de-escalation study. Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30-200,201 or placebo at study entry. Cohort 2 will begin only after safety review of all participants in Cohort 1. Participants in Cohort 2 will receive a lower dose of rDEN4delta30-200,201 or placebo. Cohort 3 will begin only after safety review of all participants in Cohort 2. Participants in Cohort 3 will receive the lowest dose of rDEN4delta30-200,201 or placebo.

After vaccination, participants will be asked to monitor their temperatures every day for 16 days. Study visits will occur every other day after vaccination until Day 16, followed by four additional visits at selected days through Day 180. Blood collection, vital signs measurement, and a targeted physical exam will occur at each study visit. Some participants will 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, as classified by intensity and severity through active and passive surveillance and separate assessments of systemic and local reactions [ Time Frame: Throughout study ]
  • Determine the number of vaccinees who have seroconverted to DEN4 up to and including Day 42 [ Time Frame: At 42 days ]


Original Primary Outcome:

  • Frequency of vaccine-related adverse events, as classified by intensity and severity through active and passive surveillance and separate assessments of systemic and local reactions
  • anti-DEN4 neutralizing antibody on Days 0, 21, 28, 42, and 180


Current Secondary Outcome:

  • Durability of antibody responses to DEN4 virus [ Time Frame: At 180 days ]
  • Frequency, quantity, and duration of viremia in each dose cohort [ Time Frame: Thoughout study ]
  • Number of vaccinees infected with vaccine virus in each dose cohort [ Time Frame: Throughout study ]
  • Duration of antibody response determined by serum neutralizing antibody [ Time Frame: At 180 days ]
  • Determine cellular targets of vaccine infection in participants willing to undergo skin biopsy [ Time Frame: Throughout study ]
  • Compare infectivity rates, safety, and immunogenicity between dose cohorts [ Time Frame: At study completion ]
  • Evaluate immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy [ Time Frame: Throughout study ]


Original Secondary Outcome:

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

Dates:
Date Received: December 27, 2005
Date Started: June 2006
Date Completion:
Last Updated: December 31, 2012
Last Verified: December 2012