Dose Escalation Trial of a Plague Vaccine, Flagellin/F1/V, in Healthy Adult Volunteers
Condition: Plague
MeSH terms: Plague
Study type: Interventional
Phase: Phase 1

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 description: 
      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 vaccine and 2
      that receive placebo. Each subject will receive an IM vaccination on Days 0 and 28. The
      initial dose to be evaluated will be 1 mcg/dose. Following assessment of safety and
      reactogenicity data of each group by the Safety Monitoring Committee the vaccine doses will
      be increased sequentially from 1, to 3, to 6, to 10 mcg/dose. Following vaccination, subjects
      will return to the clinical site on Days 1, 14, and 28 following the initial vaccination and
      on Days 1, 14, 28, 40, and 180 following the second vaccination. In addition, subjects will
      be contacted by phone on Day 3 after each vaccination to review the memory aid, query for
      adverse event (AEs)/SAEs and concomitant medications. All subjects will complete a subject
      memory aid for 15 days following each vaccination (Day 0-14). Unsolicited, non-serious AEs
      will be collected through Day 56 (Visit 8, 26-30 days following the final vaccination). SAEs
      will be collected throughout the study period Day 393 (Visit 11, 365 days + 14 days after the
      second vaccination). Blood samples for safety labs will be collected at screening, day of
      initial vaccination and at 14 days after each vaccination. Specimens will be collected for
      immunologic assays at the noted clinic visits, as well as at 6 months post the final
      vaccination.
    

Intervention name(s): Flagellin/F1/V; Placebo
Intervention type(s): Biological; Other
Intervention description(s): Flagellin/F1/V recombinant fusion protein vaccine administered by the intramuscular route on Days 0 and 28 at a dose of 1, 3, 6, or 10 micrograms (mcg). It is a clear, colorless solution.; Phosphate buffered saline (PBS) used as diluent and placebo.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Yersinia pestis, vaccine, plague, Flagellin/F1/V, Parent Protocol of 15-0104