Efficacy of an Oral, Killed Enterotoxigenic Escherichia Coli Vaccine in Prevention of Diarrhea in Egyptian Infants and Young Children

This is a randomized, double-blind, placebo-controlled clinical trial performed in Egyptian children 6-18 months of age. The primary aim of the study is to determine the protective efficacy of an oral, inactivated whole-cell enterotoxigenic Escherichia coli (ETEC) vaccine against diarrhea associated with excretion of ETEC that express a vaccine-shared antigen over a one year period of follow-up by active surveillance. The vaccine consists of a mixture of five formalin-killed ETEC bacteria expressing prevalent ETEC colonization factors and recombinant cholera toxin B-subunit (killed ETEC/rCTB vaccine). The placebo preparation is heat-killed Escherichia coli K-12 bacteria.

Study Overview

• Status: Completed
• Conditions: Diarrhea
• Intervention / Treatment: Biological: ETEC/rCTB vaccine; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 356
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Willingness of parent to have the child participate;
2. Plans to reside in catchment area continuously for at least one year

Exclusion Criteria:

1. Global developmental delay
2. Severe malnutrition
3. Chronic bedridden status
4. Serious chronic disorder requiring chronic medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Killed ETEC/rCTB vaccine; Three doses administered orally at 2-week intervals	Biological: ETEC/rCTB vaccine; Cocktail of five whole-cell, formalin-inactivated ETEC strains (total of 10^11 formalin-killed bacteria per dose) plus recombinant cholera toxin B-subunit (rCTB) (1 mg)
Placebo Comparator: Placebo; Three doses administered orally at 2-week intervals	Other: Placebo; Heat-killed, nonpathogenic E. coli K-12 bacteria (total of 10^11 heat-killed bacteria per dose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first event of diarrhea due to vaccine-preventable ETEC (VP-ETEC) as defined below, and no other copathogen.	Time to first event of diarrhea associated with excretion of VP-ETEC (defined as ETEC expressing heat-labile [LT] and heat-stable enterotoxin [ST], or ST and a vaccine-shared colonization factor [i.e., CFA/I, CS1, CS2, CS3, CS4, and/or CS5]) and no other copathogen.	365-day period starting 14 days after the third vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first event of diarrhea due to ST-only ETEC expressing a vaccine-shared CF (ST-VCF-ETEC) as defined below, and no other copathogen..	Time to first event of diarrhea associated with excretion of ST-VCF-ETEC (defined as ETEC expressing ST-only plus any vaccine-shared colonization factor [i.e., CFA/I, CS1, CS2, CS3, CS4, and/or CS5]) and no other copathogen.	365-day period starting 14 days after the third vaccination
All events of diarrhea irrespective of etiology	All events (i.e., initial plus recurrent) of diarrhea associated with excretion of any ETEC, irrespective of phenotype, and no other copathogen.	365-day period starting 14 days after the third vaccination
IgG seroconversion	IgG seroconversion (≥ twofold increase in post-vaccination endpoint titer over baseline) against rCTB and vaccine-specific colonization factors CFA/I, CS2, CS4	Baseline serum specimen is collected before first dose and post-vaccination specimen collected 14 days after third dose
IgA seroconversion	IgA seroconversion (≥ twofold increase in post-vaccination endpoint titer over baseline) against rCTB and selected vaccine-specific colonization factors CFA/I, CS2, CS4	Baseline serum specimen is collected before first dose and post-vaccination specimen collected 14 days after third dose
Number of solicited adverse events	(i.e., diarrhea, vomiting, fever by caregiver report, poor feeding, and irritability)	3-day period after each dose

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Göteborg University; Ministry of Health and Population, Egypt; International Vaccine Institute; U.S. Naval Medical Research Unit No. 3
• Investigators: Principal Investigator: Stephen Savarino, MD, MPH, Naval Medical Research Center

Study record dates

Study Major Dates

• Study Start: October 1, 1998
• Primary Completion (Actual): March 1, 2001
• Study Completion (Actual): April 1, 2002

Study Registration Dates

• First Submitted: September 21, 2015
• First Submitted That Met QC Criteria: September 21, 2015
• First Posted (Estimate): September 22, 2015

Study Record Updates

• Last Update Posted (Estimate): October 12, 2015
• Last Update Submitted That Met QC Criteria: October 7, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Diarrhea; Escherichia coli Infections
• Other Study ID Numbers: HSRRB A-7965