Clinical Trial: A Two-dose Primary Vaccination Study of a Tetravalent Dengue Virus Purified Inactivated Vaccine vs. Placebo in Healthy Adults

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I, Randomized, Placebo-Controlled, Observer-blind, Two-dose (0-28 Day Schedule) Primary Vaccination Study of Walter Reed Army Institute of Research (WRAIR) Tetravalent De

Brief Summary: The study is designed to afford a first time in humans (FTiH) safety and immunogenicity assessment of three Tetravalent Dengue Virus-Purified Inactivated Vaccine(TDENV-PIV) vaccine candidates, each formulated with a different adjuvant: either aluminum hydroxide, AS01E or AS03B (adjuvants used in Glaxo Smith Kline (GSK) Biologicals' hepatitis B candidate vaccine, malaria candidate vaccine and pandemic flu vaccine, respectively). Each vaccine candidate will contain 1 µg of purified virus antigen per each of the four DENV types. Additionally, the study will evaluate an alum adjuvanted TDENV-PIV vaccine candidate containing 4 µg of purified virus antigen per each of the four DENV types. The control group will receive a saline placebo. All experimental vaccinations will be administered according to a 2-dose schedule, 28 days apart.

Detailed Summary:
Sponsor: U.S. Army Medical Research and Materiel Command

Current Primary Outcome:

• Number, intensity, and relationship of adverse events [ Time Frame: Between Days 0-56 ]
  Occurrence, intensity and relationship to vaccination of solicited local and general adverse events (AEs) during the 7-day follow-up period post each vaccination (Day 0-6) Occurrence, intensity and relationship to vaccination of unsolicited AEs during the 28-day followup period post each vaccination (Day 0-27) Hematological and biochemical levels at study visits on Days 0, 7, 28, 35 and 56 Occurrence of serious adverse events (SAEs) from Day 0 to Day 56 Occurrence of potential immune-mediated diseases (pIMDs)* and medically attended AEs* from Day 0 to Day 56
• Neutralizing antibody titers specific to each DENV type [ Time Frame: Day 56 ]
  Trivalent and tetravalent rates
• Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type [ Time Frame: Day 56 ]
• Seropositivity rates for each DENV type [ Time Frame: Day 56 ]

Original Primary Outcome:

• Safety and reactogenicity of various TDENV-PIV formulations from Day 0 through 28 days after the second dose (Day 0 - Day 56) [ Time Frame: Up to Day 56 ]

  Safety and Reactogenicity:

  • Occurrence, intensity and relationship to vaccination of solicited local and general adverse events (AEs) during the 7-day follow-up period post each vaccination (Day 0-6)
  • Occurrence, intensity and relationship to vaccination of unsolicited AEs during the 28-day follow-up period post each vaccination (Day 0-27)
  • Hematological and biochemical levels at study visits on Days 0, 7, 28, 35 and 56
  • Occurrence of serious adverse events (SAEs) from Day 0 to Day 56
  • Occurrence of potential immune-mediated diseases (pIMDs) and medically attended AEs from Day 0 to Day 56
• Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations 28 days after the second dose (Day 56) [ Time Frame: Day 56 ]

  Humoral Immunogenicity:

  Neutralizing antibody titers specific to each DENV type at Day 56

  • Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type
  • Seropositivity rates for each DENV type
  • Trivalent and tetravalent rates

Current Secondary Outcome:

• Number of adverse events [ Time Frame: Months 4, 7, 10 and 13 ]
  Hematological and biochemical levels at study visits on Months 4, 7, 10 and Month 13 Occurrence of pIMDs and medically attended AEs from Day 0 to Month 13 Occurrence of SAEs from Day 0 to Month 13
• Neutralizing antibody titers specific to each DENV type [ Time Frame: Days 0, 7, and 28 and Months 7 and 13 ]
• Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type [ Time Frame: Days 0, 7, and 28 and Months 7 and 13 ]
• Seropositivity rates for each DENV type [ Time Frame: Days 0, 7, and 28 and Months 7 and 13 ]
• Trivalent and tetravalent rates [ Time Frame: Days 0, 7, and 28 and Months 7 and 13 ]

Original Secondary Outcome:

• Safety of various TDENV-PIV formulations, from Day 0 to Month 13 (Visits 1-11) [ Time Frame: Up to month 13 ]

  Safety:

  • Hematological and biochemical levels at study visits on Months 4, 7, 10 and Month 13
  • Occurrence of pIMDs and medically attended AEs from Day 0 to Month 13
  • Occurrence of SAEs from Day 0 to Month 13
• Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations on Days 0, 7 and 28 and Months 7 and 13 [ Time Frame: Up to month 13 ]

  Humoral Immunogenicity:

  • Neutralizing antibody titers specific to each DENV type at study visits on Days 0, 7, and 28 and Months 7 and 13

  • Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type
  • Seropositivity rates for each DENV type
  • Trivalent and tetravalent rates
• Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations 28 days after the second dose (Day 56) [ Time Frame: Day 56 ]

  Humoral Immunogenicity:

  Neutralizing antibody titers specific to each DENV type at Day 56

  • Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type
  • Seropositivity rates for each DENV type
  • Trivalent and tetravalent rates

Dates:
Date Received: August 8, 2012
Date Started: September 2012
Date Completion: February 2018
Last Updated: April 4, 2017
Last Verified: April 2017