Safety of and Immune Response to DEN4 Vaccine Component Candidate for Dengue Virus
Condition: Dengue Shock Syndrome; Dengue Hemorrhagic Fever
MeSH terms: Dengue; Hemorrhagic Fevers, Viral; Severe Dengue; Shock
Study type: Interventional
Phase: Phase 1

Summary: 
      Infection with dengue viruses is one of the leading causes of hospitalization and death in
      children in several tropical Asian counties. The World Health Organization (WHO) estimates
      that these viruses are responsible for more than 50 million cases of dengue fever (DF) and
      approximately 0.5 million cases of the more severe disease, dengue hemorrhagic fever/ shock
      syndrome (DHF/DSS) annually. Because dengue viruses are endemic in most tropical and
      subtropical regions, keeping more than 2 billion persons at risk for acquiring dengue, the
      WHO has made development of a dengue vaccine a top priority.

      The purpose of this study is to evaluate the safety and effectiveness of a candidate DEN4
      vaccine aimed at preventing infection with dengue virus serotype 4.
    

Detailed description: 
      Dengue viruses are endemic in most tropical and subtropical regions of the world with more
      than 2 billion persons at risk for acquiring dengue. There are four serotypes of dengue virus
      (DEN 1, DEN 2, DEN 3, and DEN 4) each capable of causing dengue illness ranging from mild,
      self-limited febrile illness to life-threatening disease. Because previous infection with one
      dengue serotype can increase the risk for DHF/DSS following infection with a different
      serotype, immunization would ideally provide immunity against all four dengue viral
      serotypes.

      Several live, attenuated dengue vaccines have been tested in Phase I and/or Phase II clinical
      trials. Although some have appeared promising in early trials, none have been able to meet
      the requirements for a safe and effective vaccine. Meeting these requirements has been
      particularly difficult when testing vaccines containing all four serotypes. The vaccine
      candidate in this study is live-attenuated rDEN4delta30, which will target the DEN4 serotype,
      it is a potential component for a future tetravalent dengue vaccine.

      This is a double-blind, random assignment, placebo-controlled study in healthy, adult
      volunteers. The purpose of this study is to evaluate the safety and effectiveness of a single
      dose of DEN4 vaccine. Some participants will be receiving placebo as a comparative measure,
      to better assess vaccine-associated versus non vaccine-associated adverse events.

      To qualify for participation in the study, volunteers will undergo an eligibility screening
      which will include medical history, physical exam, hematology testing, liver and renal
      function testing, coagulation studies, human immunodeficiency virus (HIV) and hepatitis B and
      C screening, urinalysis, and screening for pervious flavivirus infection. Urine pregnancy
      testing will also be required for female volunteers.

      Duration of individual participation in the study is approximately 26 weeks following
      vaccination on Study Day 0. Volunteers will be randomly assigned to receive either
      rDEN4delta30 or placebo; 50 participants will receive the vaccine, 20 will receive placebo.
      On the day of vaccination, all volunteers will be reassessed by study personnel to ensure
      continued eligibility, vital signs will be taken, and a physical exam will be performed.
      Female participants will also have a pregnancy test and review of acceptable pregnancy
      prevention methods. Eligible participants will receive a vaccination of Study Day 0, followed
      by a 30 minute post vaccination assessment for adverse events. After vaccination, volunteers
      will be evaluated in the clinic approximately every other day for the first 16 days if study.

      During the course of study, volunteers will have blood drawn and clinical evaluations
      performed on Study Days 21, 28, 42, and 180 post-vaccination. All participants will be asked
      to record oral temperatures 3 times a day for the first 16 days post-vaccination.
    

Intervention name(s): DEN4 Vaccine Candidate; DEN4 Vaccine Placebo
Intervention type(s): Biological; Biological
Intervention description(s): DEN4 Vaccine Candidate
Participants will receive a single immunization on Study Day 0. Vaccine will be delivered by subcutaneous injection in the upper arm, at a volume of 0.5 mL.; DEN4 Vaccine Placebo
Participants will receive a single immunization on Study Day 0. Placebo will be delivered by subcutaneous injection in the upper arm, at a volume of 0.5 mL.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Dengue virus; Vaccine; DEN4; Dengue