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

Study Overview
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Brief Summary
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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.

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

Conditions
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Diarrhea

Intervention / Treatment
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* Biological: ETEC/rCTB vaccine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willingness of parent to have the child participate; Plans to reside in catchment area continuously for at least one year Exclusion Criteria: Global developmental delay Severe malnutrition Chronic bedridden status Serious chronic disorder requiring chronic medication

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Killed ETEC/rCTB vaccine<br>Three doses administered orally at 2-week intervals | Biological: ETEC/rCTB vaccine<br>* 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)<br>|
| Placebo Comparator: Placebo<br>Three doses administered orally at 2-week intervals | Other: Placebo<br>* Heat-killed, nonpathogenic E. coli K-12 bacteria (total of 10^11 heat-killed bacteria per dose)<br>|

What is the study measuring?
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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 |