Clinical Trial: TY800 Dose Escalation (Typhoid)

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

Official Title: A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation, In-Patient Phase I/II Study to Determine the Safety and Immunogenicity of Ty800 in Healthy Adult Subjects

Brief Summary: The purpose of this research study is to determine whether a new vaccine for typhoid fever is safe and effective. This study will also look at what effects (good and bad) this new vaccine, Ty800, has on the volunteers. The study will determine the highest dose of Ty800 that can be given without causing severe side effects. About 54 healthy males and females, ages 18-45 inclusive, in the Cincinnati metropolitan area will be enrolled in this study. They will be in the study for approximately 7 months, which includes a one month screening period, study product administration on Day 0, a 10-day hospital stay, an outpatient period on Days 9-28 with 4 follow-up visits, and safety follow-up phone calls at 2 and 6 months after hospital discharge. Researchers hope that this trial will help produce a vaccine that combines a high level of durable protective immunity with simplicity of administration and minimal reaction to the vaccine.

Detailed Summary: Typhoid fever is a generalized infection of the reticuloendothelial system (spleen, liver, and bone marrow), gut-associated lymphoid tissue and gall bladder caused by Salmonella enterica serovar Typhi (S typhi). Humans are the only known natural host and reservoir for S typhi. Typhoid bacilli are transmitted by the fecal-oral route by contaminated drinking water or food. The ideal typhoid vaccine would combine high levels of durable protective immunity with simplicity of administration and minimal reactogenicity. The primary objective of this study is to assess the safety of Ty800 oral typhoid vaccine when administered as a single dose over a range of doses (5 x 10^7, 5 x 10^8, and 5 x 10^9 cfu) in healthy adult subjects compared to placebo. The primary endpoint is safety of Ty800 at the dose levels administered compared to placebo as determined by absence of bacteremia, absence of the diagnosis of typhoid fever as confirmed by a positive blood culture for the Ty800 vaccine organism, and by verifying that the null phoP/phoQ phenotype is retained by the isolated shed vaccine organism. Safety variables will be assessed by the reported incidence of adverse events (AE), blood cultures, and changes in vital signs, physical examination, and routine laboratory parameters over time at each vaccine dose level compared to placebo. The secondary objectives of this study are: to evaluate the immunogenicity of a single oral dose administration of Ty800 over a range of doses in healthy adult subjects; to evaluate the Ty800 vaccine dose response by comparing the immunogenicity profiles of each dose level; and to evaluate the shedding profile of Ty800 by determining the quantity and duration of shedding for each dose level. The tertiary objectives of this study include: evaluating, in a substudy, single nucleotide polymorphisms (SNPs) in candidate genes, e.g., IL-8 and interferon gamma, that may influence the immune response or persistent shedding of the vaccine organism and evalua
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome: Assess the safety of Ty800 oral typhoid vaccine when administered as a single dose over a range of doses (5 x 10^7, 5 x 10^8, 5 x 10^9 cfu) in healthy adult subjects compared to placebo. [ Time Frame: Duration of study. ]

Original Primary Outcome:

Current Secondary Outcome:

  • To evaluate the shedding profile of Ty800 by determining the quantity and duration of shedding for each dose level. Spread of the vaccine organism to placebo subjects will also be monitored as an outcome variable. [ Time Frame: Days 1-8, 11, 14, and 28. ]
  • To evaluate the immunogenicity of the single oral dose administration of Ty800 over a range of doses in healthy adult subjects. [ Time Frame: At intervals after vaccination between Days 7 through 28. ]
  • To evaluate the Ty800 vaccine dose response by comparing the immunogenicity profiles of each dose level. [ Time Frame: At intervals after vaccination between Days 7 through 28. ]


Original Secondary Outcome:

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

Dates:
Date Received: December 22, 2005
Date Started: February 2006
Date Completion:
Last Updated: June 9, 2011
Last Verified: February 2010