Tetravalent Chimeric Dengue Vaccine Trial
Condition: Dengue
MeSH terms: Dengue
Study type: Interventional
Phase: Phase 1

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 description: 
      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.
    

Intervention name(s): Placebo (SC); Placebo (ID); Modified Live Tetravalent Chimeric Dengue Vaccine (SC); Modified Live Tetravalent Chimeric Dengue Vaccine (ID)
Intervention type(s): Drug; Drug; Biological; Biological
Intervention description(s): Phosphate buffered saline administered subcutaneously.; Phosphate buffered saline administered intradermally.; DENVax is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: DEN-2 PDK-53 (DENVax-2), DEN-2/1 chimera (DENVax-1), DEN-2/3 chimera (DENVax-3) and DEN-2/4 chimera (DENVax-4). The drug product is formulated in buffer and stored frozen. Low dose contains (dose volume 0.1 mL): D1: 8 x 10^3, D2: 5 x 10^3, D3: 1 x 10^4, and D4: 2 x 10^5, total virus dose [plaque forming units (PFU)]: 2.2 x 10^5. High dose contains (dose volume 0.1 mL): D1: 2 x 10^4, D2: 5 x 10^4, D3: 1 x 10^5, and D4: 3 x 10^5, total virus dose (PFU): 4.7 x 10^5. DENVax administered subcutaneously.; DENVax is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: DEN-2 PDK-53 (DENVax-2), DEN-2/1 chimera (DENVax-1), DEN-2/3 chimera (DENVax-3) and DEN-2/4 chimera (DENVax-4). The drug product is formulated in buffer and stored frozen. Low dose contains (dose volume 0.1 mL): D1: 8 x 10^3, D2: 5 x 10^3, D3: 1 x 10^4, and D4: 2 x 10^5, total virus dose [plaque forming units (PFU)]: 2.2 x 10^5. High dose contains (dose volume 0.1 mL): D1: 2 x 10^4, D2: 5 x 10^4, D3: 1 x 10^5, and D4: 3 x 10^5, total virus dose (PFU): 4.7 x 10^5. DENVax administered intradermally.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Dengue, vaccine, flavivirus