Evaluation of Safety, Reactogenicity and Immunogenicity of Fractional-dose Inactivated Polio Vaccine (fIPV) Given Intradermally With Double Mutant Enterotoxigenic Escherichia Coli Heat Labile Toxin (dmLT) Adjuvant
Condition: Polio
MeSH terms: Poliomyelitis; Escherichia coli Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Polio is a serious disease that can cause paralysis and death. It is caused by a virus and
      can be prevented by vaccine. The World Health Organization's (WHO) Global Polio Eradication
      Initiative is trying to get rid of all polio disease around the world. Researchers want to
      help by testing a new vaccine.

      In many countries, people are vaccinated with oral polio vaccine (OPV) given by mouth during
      childhood. OPV is good at giving immunity (protection from polio) in the body and the
      gastrointestinal (GI) tract. Immunity in the GI tract is called mucosal immunity. The
      downsides of using OPV are that it can be shed into the environment in people's feces after
      vaccination where it can infect people who are not vaccinated, and it can cause paralysis in
      2-4 of every one million children vaccinated with OPV. The United States (U.S.) stopped
      giving any OPV to people for vaccinations in the 1990's. Since then, a polio vaccine called
      inactivated polio vaccine (IPV) is given as an injection for routine childhood immunizations
      in the U.S. You cannot get polio infection from IPV and it will not be shed into the
      environment.

      In 2016, the WHO started a plan to help other countries gradually get rid of OPV. The
      downside of using IPV by itself is that, unlike OPV, it doesn't give enough mucosal immunity
      to protect people living in places where there is still polio. There are also supply
      shortages of IPV, which is a problem if there are outbreaks of polio. For the supply of IPV
      to help more people, it is safe and effective to use a tiny dose of IPV injected under the
      top layer of skin (intradermal or ID injection) rather than getting the full dose in the
      muscle. This is called a fractional dose of IPV, or fIPV.

      To help stop using OPV globally, a better fIPV vaccine is needed. fIPV vaccine needs a
      substance to help stimulate a mucosal immune response. dmLT is a substance that has been
      shown to stimulate a mucosal immune response. It has been shown to be safe and effective in
      both humans and animals, both by itself and when given with other vaccines.

      This study will test a mixture of fIPV-dmLT given intradermally (under the outer layer of the
      skin). This is the first study done in humans to give this combination intradermally. The IPV
      vaccine has already been approved by the FDA. The fIPV-dmLT vaccine has not been approved by
      the FDA.
    

Detailed description: 
      This single site study conducted at The University of Vermont will enroll 30 healthy male and
      female adult volunteers aged 18-45 years with no history of oral polio vaccination for a
      Phase I randomized controlled double-blind trial evaluating the safety, reactogenicity and
      immunogenicity of a single dose of fIPV-dMLT versus a single dose of fIPV administered
      intradermally. Study volunteers will be screened with eligible volunteers enrolled who will
      randomized to receive a single dose of fIPV-dmLT or fIPV (2:1) on study day 0. The primary
      study objective is to determine the safety and reactogenicity of a single dose of adjuvanted
      fIPV-dmLT vaccine in healthy adults, as assessed by the frequency of systemic and local
      injection site adverse reactions (ARs) defined as vaccine-related adverse events (AEs),
      graded by severity, occurring within 28 days of dosing. Secondary objectives are to determine
      the safety of a single dose of adjuvanted fIPV-dmLT vaccine in healthy adults, as assessed by
      the percentage of subjects with at least one vaccine-related serious adverse event (SAE)
      occurring within 28 days of dosing. In addition, the systemic immune response to a single
      dose of vaccine in healthy adults, as assessed by poliovirus-specific serum neutralizing
      antibody responses in fIPV-dmLT recipients versus fIPV only recipients will be examined.
    

Intervention name(s): dmLT; fIPV
Intervention type(s): Biological; Biological
Intervention description(s): double mutant [LT(R192G/L211A)] Enterotoxigenic Escherichia coli heat labile toxin (dmLT); fractional-dose inactived polio vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: inactivated polio vaccine (IPV); fractional-dose inactivated polio vaccine (fIPV); double mutant [LT(R192G/L211A)] Enterotoxigenic E coli heat toxin (dmLT)