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

Diarrhea Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02556996
• Other study ID #: HSRRB A-7965
• Status: Completed
• Phase: Phase 3
• First received: September 21, 2015
• Last updated: October 7, 2015
• Start date: October 1998
• Est. completion date: April 2002

Study information

• Verified date: October 2015
• Source: U.S. Army Medical Research and Materiel Command
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 356
• Est. completion date: April 2002
• Est. primary completion date: March 2001
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Months to 18 Months

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diarrhea

Intervention

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)

Other:
• Placebo
Heat-killed, nonpathogenic E. coli K-12 bacteria (total of 10^11 heat-killed bacteria per dose)

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
U.S. Army Medical Research and Materiel Command	Egyptian Ministry of Health and Population, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Göteborg University, International Vaccine Institute, U.S. Naval Medical Research Unit No. 3

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Number of solicited adverse events	(i.e., diarrhea, vomiting, fever by caregiver report, poor feeding, and irritability)	3-day period after each dose	Yes