Clinical Trial: Safety of and Immune Response of a 2-dose Regimen of rDEN1delta30 Dengue Virus Vaccine

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

Official Title: Safety and Immunogenicity of a 2-Dose Regimen of rDEN1delta30 Dengue Serotype 1 Vaccine With Boosting at 4 Versus 6 Months

Brief Summary: Dengue fever, 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 of and immune response to a 2-dose regimen of a new monovalent dengue virus vaccine. This study will test the dengue virus vaccine DEN1delta30 in healthy adults.

Detailed Summary:

Dengue viruses account for more than 50 million cases of dengue fever and one half million cases annually of dengue hemorrhagic fever/shock syndrome. Dengue virus infections can cause illness ranging from mild, self-limited febrile illness to life threatening diseases. The goal of dengue vaccine development is to induce a long-lived antibody response against all four dengue serotypes. The rDEN1delta30 vaccine is a live attenuated dengue virus vaccine that may be protective against dengue serotype 1 (DEN1). The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of a 2-dose regimen of rDEN1delta30 dengue virus vaccine. The regimen will differ in when the second booster shot of the vaccine is given.

This study will last 162 days (about 23 weeks) for those participants in Cohort 1, and 222 days (about 32 weeks) for those in Cohort 2. Participants in Cohort 1 will be randomly assigned to receive rDEN1delta30 vaccine or placebo on Study Day 0 and Study Day 120. Participants in Cohort 2 will be randomly assigned to receive rDEN1delta30 vaccine or placebo on Study Day 0 and Study Day 180.

There will be a total of 25 visits for each cohort. For both cohorts, the first and second vaccination days will include a physical exam and blood and urine collection, vital signs measurements, and receipt of the vaccine. A 30 minute observation period will follow vaccination. Participants will take their temperature at home three times a day for the first 16 days and report it in a diary. At all other study visits, vital signs measurements, a physical exam, and blood and/or urine collection will occur. At selected study visits, participants will turn in their diary cards.

Some participants may be asked to join an optional skin biopsy substudy.


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

Current Primary Outcome:

  • To determine the safety and immunogenicity of a two-dose regimen of the rDEN1delta30 vaccine given as two doses separated by four or six months [ Time Frame: Throughout study ]
  • To determine the optimum interval between first and second dose of rDEN1delta30 vaccine, as assessed by neutralizing antibody response to DEN1 induced by the vaccine [ Time Frame: At 4 and 6 weeks after first and second vaccination ]


Original Primary Outcome:

  • To determine the safety and immunogenicity of a 2-dose regimen of the rDEN1delta30 vaccine given as two doses separated by four or six months
  • To determine the optimum interval between first and second dose of rDEN1delta30 vaccine, as assessed by neutralizing antibody response to DEN1 induced by the vaccine [ Time Frame: at 4 and 6 weeks after first and second vaccination. ]


Current Secondary Outcome:

  • To assess the frequency, quantity, and duration of viremia following each vaccine dose, based on the mean peak viremia, mean day of onset, and mean duration of viremia [ Time Frame: Throughout study ]
  • To determine the number of vaccinees infected with rDEN1delta30 virus [ Time Frame: Throughout study ]
  • To compare the infectivity rates, safety, and immunogenicity between dose 1 and 2 within a cohort and between cohorts [ Time Frame: Throughout study ]
  • To evaluate the immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy [ Time Frame: Throughout study ]
  • To evaluate the phenotype and activation of peripheral blood mononuclear cells (PBMCs) at primary infection and challenge with DEN1 [ Time Frame: Throughout study ]


Original Secondary Outcome:

  • To assess the frequency, quantity, and duration of viremia following each vaccine dose, based on the mean peak viremia, mean day of onset, and mean duration of viremia
  • To determine the number of vaccinees infected with rDEN1delta30 virus
  • To compare the infectivity rates, safety, and immunogenicity between dose 1 and 2 within a cohort and between cohorts
  • To evaluate the immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy
  • To evaluate the phenotype and activation of peripheral blood mononuclear cells (PBMCs) at primary infection and challenge with DEN1


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

Dates:
Date Received: May 11, 2007
Date Started: May 2007
Date Completion:
Last Updated: January 11, 2010
Last Verified: January 2008