NCT00654108

Safety and Immunogenicity of Peru-15-pCTB in Healthy Adult Subjects

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) in Healthy Adult Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 62 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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.

Conditions

• Gastroenteritis Escherichia Coli

Interventions

Type	Name	Description
DRUG	Ciprofloxacin	500 milligrams(mg) will be administered orally twice daily for 5 days.
BIOLOGICAL	Peru-15-pCTB	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.
OTHER	Sodium bicarbonate/Ascorbic Acid/Aspartame Buffer	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.

Timeline

• Start date: 2008-06-02
• Primary completion: 2010-05-30
• Completion: 2010-12-31
• First posted: 2008-04-07
• Last updated: 2021-07-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study