Safety and Immunogenicity of Peru-15-pCTB in Healthy Adult Subjects
Condition: Gastroenteritis Escherichia Coli
MeSH terms: Escherichia coli Infections; Gastroenteritis
Study type: Interventional
Phase: Phase 1

Summary: 
      Enterotoxigenic Escherichia (E.) coli (ETEC) bacteria are the main cause of traveler's
      diarrhea and are significant pathogens affecting children and elderly individuals of
      developing countries. The purpose of the study is to determine the safety of the ETEC-Cholera
      vaccine and the body's ability to protect itself against ETEC and cholera infection after
      receiving the vaccine. The study will enroll a total of 64 healthy volunteers, 18 to 45 years
      old at the Cincinnati Children's Hospital. The study will provide increasing doses of the
      vaccine or placebo (inactive substance) to 4 groups consisting of 16 participants each.
      Participants will remain in the inpatient unit for observation for about 11 days. All
      subjects will be treated with Cipro, an antibiotic, for 5 days. Study procedures include:
      blood samples, vital signs, physical examinations, and stool samples. Volunteers will be
      involved in the study for about 8 months including telephone contacts.
    

Detailed description: 
      Enterotoxigenic Escherichia coli (ETEC) are the principal single cause of traveler's diarrhea
      and are a significant pathogen affecting children and elderly individuals of developing
      countries. ETEC infections result in approximately 600 million total cases of diarrhea
      worldwide annually, with an estimated 280 million cases and over 400,000 deaths in children
      less than 5 years of age. The proposed study is a randomized, double-blind, placebo
      controlled, dose-escalation, inpatient Phase I study to determine the safety and
      immunogenicity of a single oral dose of a combined live, attenuated, enterotoxigenic
      Escherichia coli (ETEC)-cholera vaccine (Peru-15 pCTB). A total of 64 healthy subjects, 18 to
      45 years old will be enrolled in this study. Subject participation duration is up to 8
      months. Sequential cohorts of 16 eligible subjects will be randomized in a 3:1 ratio to
      receive the assigned dose of ETEC-cholera vaccine or placebo (bicarbonate buffer only),
      respectively. The first dose level cohort (1x10^7 colony forming units) will be divided into
      2 groups. Initially, 4 subjects will be enrolled, treated, and observed to ensure the
      tolerability of this dose level through Day 28. In the absence of any stopping rules,
      enrollment and dosing will proceed with the remaining 12 subjects of this cohort. Thereafter,
      dose escalation and subject enrollment will proceed in a step-wise fashion. A Safety
      Monitoring Committee will be convened for this study, and will review available safety data
      through the Day 28 post-vaccination visits for each cohort prior to making a recommendation
      to the Sponsor on advancement to the next dose level. The study will be conducted at
      Cincinnati Children's Hospital. The primary objective of this study will be to assess the
      safety of a combined ETEC-cholera vaccine [Peru-15-pCTB (Cholera toxin B-subunit)] when
      administered as a single oral dose over a range of doses in healthy adult subjects compared
      to placebo at day 28 post-vaccination. The secondary objectives will be: to assess long-term
      safety follow-up from immunization through Month 6 post vaccination; to evaluate the
      immunogenicity of a single oral dose of ETEC-cholera vaccine over a range of doses in healthy
      adult subjects; and to evaluate the shedding profile of the ETEC-cholera vaccine organisms in
      stool for a period of 7 days.
    

Intervention name(s): Ciprofloxacin; Peru-15-pCTB; Sodium bicarbonate/Ascorbic Acid/Aspartame Buffer
Intervention type(s): Drug; Biological; Other
Intervention description(s): 500 milligrams(mg) will be administered orally twice daily for 5 days.; Live attenuated oral combined ETEC-cholera (Peru-15 pCTB) vaccine co-administered with bicarbonate buffer solution; vaccine dose levels 1 X 10^7; 1 X 10^8; 1 X 10^9; and 1 X 10^10.; Buffer solution: 2.5 grams (g) Sodium Bicarbonate powder, 1.65 g Ascorbic Acid and 25 mg Aspartame, in 100 milliliters (mL) water for injection.
Intervention MeSH terms: Ascorbic Acid; Ciprofloxacin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: cholera; diarrhea; Escherichia coli; vaccine