Clinical Trial: Dose Escalation Trial of a Plague Vaccine, Flagellin/F1/V, in Healthy Adult Volunteers

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

Official Title: A Phase I Safety and Immunogenicity Dose Escalation Trial of Plague Vaccine, Flagellin/F1/V, In Healthy Adult Volunteers

Brief Summary: Plague is an infectious disease of animals and humans caused by bacteria, Yersinia pestis. Modern antibiotics are effective against plague, but if an infected person is not treated promptly the disease is likely to cause illness or death. The purpose of this study is to evaluate at the safety, immunogenicity (bodily defense reaction), and tolerability of a new research vaccine. Up to 48 people will be enrolled in this study at the Center for Vaccine Development at Saint Louis University. Four groups of 12 volunteers will be given vaccine or placebo (inactive substance) one group at a time starting with the lowest dose working up to the highest dose. Shots will be given in the arm 2 times separated by 28 days. Study procedures include: physical exam, blood samples, and recording temperature and side effects in a memory aid. Participants will be involved in study related procedures for about 13 months.

Detailed Summary: Yersinia (Y.) pestis, a gram-negative coccobacillus, causes an acute and often fatal disease that may appear in 1 of several major manifestations: bubonic, septicemic, and pneumonic. Transmission to humans most commonly occurs via a bite by infectious fleas and is associated with regional lymphadenopathy or bubo. Pneumonic plague would be the most likely outcome in the case of a bio-terrorism attack. Currently, there is no effective licensed vaccine that protects against pneumonic plague. The investigational product, flagellin/F1/V in phosphate-buffered saline, pH 6.2, is a vaccine that is designed to provide protection against respiratory exposure to Y. pestis, i.e., pneumonic plague. The general hypothesis to be tested is that the flagellin/F1/V vaccine will induce a robust humoral immune response against the F1 and V antigens of Y. pestis without serious adverse events (SAEs) when the vaccine is given intramuscularly (IM) on 2 occasions separated by about 28 days at doses of 1, 3, 6 and 10 micrograms (mcg). Since the major rationale for this vaccine is protection against respiratory exposure to Y. pestis following a bio-terrorism attack, the initial study population will be 18-45 year old healthy volunteers. The primary objective of this study is to assess the safety and immunogenicity of escalating dosages of Flagellin/F1/V vaccine among healthy subjects given 2 doses of vaccine by the IM route on Days 0 and 28. The secondary objective of this study is to evaluate the reactogenicity and cell mediated immune responses of escalating dosages of Flagellin/F1/V vaccine among healthy subjects when given 2 doses of vaccine by the IM route on Days 0 and 28. Participants will include up to 48 healthy male and female volunteers. This study is designed as a randomized, placebo controlled, double-blind (within dosing group), dose escalation Phase I study. The study will consist of 4 groups to be dosed sequentially. Each group will consist of 10 individuals that receive vacc
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Incidence of Grade 3 or above laboratory toxicities associated with vaccination for each dose group. [ Time Frame: Through Day 42 (14 days after the second vaccination). ]
  • Incidence of serious adverse events (SAEs)associated with vaccination for each dose group. [ Time Frame: Throughout the duration of the study (Visit 11, 365 + 14 days after the second vaccination or through termination visit, if terminated early). ]
  • Peak antibody titer [immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for F1 and V antigen] for each dose group as determined by analysis of serum samples. [ Time Frame: Days: 0, 14, 28, 42, 56, 68 and 208. ]


Original Primary Outcome:

  • Peak antibody titer [immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) for F1 and V antigen] for each dose group as determined by analysis of serum samples. [ Time Frame: Days: 0, 14, 28, 42, 56, 68 and 208. ]
  • Incidence of Grade 3 or above laboratory toxicities associated with vaccination for each dose group. [ Time Frame: Through Day 42 (14 days after the second vaccination). ]
  • Incidence of serious adverse events (SAEs)associated with vaccination for each dose group. [ Time Frame: Throughout the duration of the study (Visit 11, 365 + 14 days after the second vaccination or through termination visit, if terminated early). ]


Current Secondary Outcome:

  • Distribution of the cytokine expression levels in peripheral blood mononuclear cells (PBMCs) following ex vivo stimulation for each dose group. [ Time Frame: Day 0, 14, 42, 56, and 68. ]
  • Occurrence of unsolicited adverse events (AEs) for each dose group. [ Time Frame: Within 28 days of each vaccination. ]
  • Occurrence of systemic reactogenicity symptoms for each dose group. [ Time Frame: Within 15 days (Day 0-14) of each vaccination. ]
  • Occurrence of localized reactogenicity symptoms for each dose group. [ Time Frame: Within 15 days (Day 0-14) of each vaccination. ]
  • Assessment of cytokine responses (TNF-alpha, IL-6 and IL-1 beta) as measured in serum samples. [ Time Frame: Serum samples obtained on the day of vaccination, and on Visit 3 and 6 (1 day after each vaccination) and Visit 4 and 7 (14 days after each vaccination). ]


Original Secondary Outcome:

  • Assessment of cytokine responses (TNF-alpha, IL-6 and IL-1 beta) as measured in serum samples. [ Time Frame: Serum samples obtained on the day of vaccination, and on Visit 3 and 6 (1 day after each vaccination) and Visit 4 and 7 (14 days after each vaccination). ]
  • Occurrence of localized reactogenicity symptoms for each dose group. [ Time Frame: Within 15 days (Day 0-14) of each vaccination. ]
  • Occurrence of unsolicited adverse events (AEs) for each dose group. [ Time Frame: Within 28 days of each vaccination. ]
  • Distribution of the cytokine expression levels in peripheral blood mononuclear cells (PBMCs) following ex vivo stimulation for each dose group. [ Time Frame: Day 0, 14, 42, 56, and 68. ]
  • Occurrence of systemic reactogenicity symptoms for each dose group. [ Time Frame: Within 15 days (Day 0-14) of each vaccination. ]


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

Dates:
Date Received: June 23, 2011
Date Started: February 2012
Date Completion:
Last Updated: January 28, 2016
Last Verified: October 2014