Phase 1 Study of dmLT ID Vaccination in Healthy Adults
Condition: Gastroenteritis Escherichia Coli
MeSH terms: Escherichia coli Infections; Gastroenteritis
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is to determine the safety and immunogenicity of an Enterotoxigenic Escherichia
      coli (ETEC) candidate vaccine, attenuated recombinant Double Mutant Heat-Labile Toxin (dmLT)
      from ETEC, administered by the Intradermal (ID) route. The sample size has been determined
      based on the historic sample, not on power calculations.The study will involve 99 subjects
      (83 vaccinees and 16 placebo controls) in 4 consecutive cohorts of 16 individuals each (13
      vaccinees and 3 placebo controls) and the final cohort of 35 (31 vaccinees and 4 placebos)
      subjects. The primary objective is to assess the safety and tolerability of dmLT vaccine when
      administered in three doses intradermally over a range of dosages in healthy adult subjects.
    

Detailed description: 
      This is a randomized, double-blinded, single site outpatient Phase 1 study in healthy adults
      to determine the safety and immunogenicity of an Enterotoxigenic Escherichia coli (ETEC)
      candidate vaccine, attenuated recombinant Double Mutant Heat-Labile Toxin (dmLT) from ETEC,
      administered by the Intradermal (ID) route. The sample size has been determined based on the
      historic sample, not on power calculations.The study will involve 99 subjects (83 vaccinees
      and 16 placebo controls) in 4 consecutive cohorts of 16 individuals each (13 vaccinees and 3
      placebo controls) and the final cohort of 35 (31 vaccinees and 4 placebos) subjects. A total
      of 16 subjects (to retain 10 vaccinees and 1 placebo evaluable subjects) in each cohort 1-4
      will initially be recruited, 13 subjects each will receive three separate doses of dmLT
      intradermally at 1, 22 and 43-day, and 3 subjects in each cohort will receive three doses of
      a placebo (saline) in a blinded fashion. Because of concerns of local reactogencity in cohort
      3, cohort 4 will include a sentinel group of 6 subjects that is assessed prior to dosing the
      remaining 10 subjects. Proceeding to the remaining subjects will be based on review of safety
      data obtained from days 1-14 after the first dose in the sentinel subjects by the ISM, PI and
      MM. As this is an outpatient study, subjects will receive their vaccinations and remain in
      clinic for observation for a minimum of 30 minutes. Safety data will be reviewed by Safety
      Monitoring Team or Committee. Subjects may be replaced to ensure 10 evaluable subjects in
      each single cohort, as defined by receiving all 3 vaccine doses. If replacement subjects will
      be included if needed and they will be randomized per cohort as a single group to include 1
      subject to receive placebo to maintain the blind and ensure there are one placebos in each
      cohort. Final confirmatory cohort will include up to 35 vaccinees randomly selected to
      receive either 1, 2 or 3 vaccine doses or placebo. The study duration is approximately 1.5-2
      years, including 6 months of follow-up and approximately 9 months for subject duration. The
      primary objective is to assess the safety and tolerability of dmLT vaccine when administered
      in three intradermal doses over a range of dosages levels in healthy adult subjects. The
      secondary objectives are: 1. To assess long-term safety follow-up from immunization through 6
      months post last vaccination; 2. Following ID administration of dmLT vaccine over a range of
      dosages levels evaluate dmLT-specific immune response by assays.
    

Intervention name(s): Placebo; Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine
Intervention type(s): Other; Biological
Intervention description(s): Placebo: 0.9% Sodium Chloride injection.; LT(R192G/L211A), or dmLT is formulated as a freeze-dried (lyophilized), white to off-white cake, containing 700mcg of vaccine protein in a 3 ml, multi-dose.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: dmLT; Enteric; Escherichia coli Infections; Shigella; Toxin LTR192G/L211A