Safety of Sublingual dmLT for ETEC
Condition: Gastroenteritis Escherichia Coli
MeSH terms: Escherichia coli Infections; Gastroenteritis
Study type: Interventional
Phase: Phase 1

Summary: 
      A Phase 1 dose escalating study of ETEC candidate vaccine to determine safety and
      immunogenicity of a multi-dose regimen in healthy adult volunteers. The study will be
      conducted at Cincinnati Children's Hospital Medical Center (CCHMC). The primary objectives
      assess the safety and tolerability of dmLT vaccine when administered in three doses
      sublingually over a range of dosages in healthy adult subjects. The secondary objectives
      assess long-term safety follow-up from immunization through Month 7 post vaccination,
      following three SL doses of dmLT vaccine over a range of dosages and comparing with three
      doses of a comparable dosage of oral vaccine. The study subject population is 52 healthy
      adult male and female subjects, ages 18 to 45. Subject participation duration is
      approximately 8 months with study duration of approximately 1.5-2 years, including 6-7 months
      of follow-up.
    

Detailed description: 
      Despite the public health burden of Enterotoxigenic Escherichia coli (ETEC) on travelers,
      deployed soldiers and, most significantly, young children in the developing world, there is
      no licensed vaccine against ETEC enteritis.This is a Phase 1 study in healthy adults to
      determine the safety and immunogenicity of an ETEC candidate vaccine, attenuated recombinant
      dmLT from ETEC, administered by the SL (Sublingual) or Oral Immunization. The study subject
      population is 52 healthy adult male and female subjects, ages 18 to 45. Subject participation
      duration is approximately 8 months with study duration of approximately 1.5-2 years,
      including 6-7 months of follow-up. Potential risks include subjects could develop varying
      degrees of diarrhea or other gastrointestinal symptoms (such as nausea, abdominal pain or
      cramping, gas, and decreased appetite). Blood drawing may be associated with pain and
      bruising at the site and rarely, with fainting or seizure. There is no direct benefit to
      subjects from participating in this study but the potential benefits to children and adults
      who may receive a future beneficial vaccine based on the results of this trial justify the
      more than minimal risk of the subjects who will participate in this trial. The primary
      objective is to assess the safety and tolerability of dmLT vaccine when administered in three
      doses sublingually over a range of dosages in healthy adult subjects. The secondary
      objectives are to assess long-term safety follow-up from immunization through Month 7 post
      vaccination, and following three SL doses of dmLT vaccine over a range of dosages and
      comparing with three doses of a comparable dosage of oral vaccine.
    

Intervention name(s): Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine; Recombinant Double Mutant Heat-Labile Toxin LT(R192G/L211A) (dmLT) Oral enterotoxigenic Escherichia coli (ETEC) Vaccine
Intervention type(s): Biological; Biological
Intervention description(s): Attenuated, Recombinant Double Mutant Heat-Labile Toxin (dmLT) from Enterotoxigenic Escherichia coli (ETEC), LT(R192G/L211A); lot 1575. Subjects in 5 cohorts receive 3 doses ranging from 1 mcg to 50 mcg.; Attenuated, Recombinant Double Mutant Heat-Labile Toxin (dmLT) from Enterotoxigenic Escherichia coli (ETEC), LT(R192G/L211A); lot 1575. Subjects in 5b cohort receive 3 doses of 25 mcg.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Escherichia coli Infections; ETEC Candidate Vaccine; Immunogenicity