search
Back to results

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

Primary Purpose

Diarrhea

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ETEC/rCTB vaccine
Placebo
Sponsored by
U.S. Army Medical Research and Development Command
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Diarrhea

Eligibility Criteria

6 Months - 18 Months (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Killed ETEC/rCTB vaccine

    Placebo

    Arm Description

    Three doses administered orally at 2-week intervals

    Three doses administered orally at 2-week intervals

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    IgG seroconversion
    IgG seroconversion (≥ twofold increase in post-vaccination endpoint titer over baseline) against rCTB and vaccine-specific colonization factors CFA/I, CS2, CS4
    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
    Number of solicited adverse events
    (i.e., diarrhea, vomiting, fever by caregiver report, poor feeding, and irritability)

    Full Information

    First Posted
    September 21, 2015
    Last Updated
    October 7, 2015
    Sponsor
    U.S. Army Medical Research and Development Command
    Collaborators
    U.S. Naval Medical Research Unit No. 3, Ministry of Health and Population, Egypt, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), International Vaccine Institute, Göteborg University
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT02556996
    Brief Title
    Efficacy of an Oral, Killed Enterotoxigenic Escherichia Coli Vaccine in Prevention of Diarrhea in Egyptian Infants and Young Children
    Official Title
    Efficacy of an Oral, Killed Enterotoxigenic Escherichia Coli Vaccine in Prevention of Diarrhea in Egyptian Infants and Young Children
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    October 1998 (undefined)
    Primary Completion Date
    March 2001 (Actual)
    Study Completion Date
    April 2002 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    U.S. Army Medical Research and Development Command
    Collaborators
    U.S. Naval Medical Research Unit No. 3, Ministry of Health and Population, Egypt, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), International Vaccine Institute, Göteborg University

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Diarrhea

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    356 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Killed ETEC/rCTB vaccine
    Arm Type
    Experimental
    Arm Description
    Three doses administered orally at 2-week intervals
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Three doses administered orally at 2-week intervals
    Intervention Type
    Biological
    Intervention Name(s)
    ETEC/rCTB vaccine
    Intervention Description
    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)
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    Heat-killed, nonpathogenic E. coli K-12 bacteria (total of 10^11 heat-killed bacteria per dose)
    Primary Outcome Measure Information:
    Title
    Time to first event of diarrhea due to vaccine-preventable ETEC (VP-ETEC) as defined below, and no other copathogen.
    Description
    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.
    Time Frame
    365-day period starting 14 days after the third vaccination
    Secondary Outcome Measure Information:
    Title
    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..
    Description
    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.
    Time Frame
    365-day period starting 14 days after the third vaccination
    Title
    All events of diarrhea irrespective of etiology
    Description
    All events (i.e., initial plus recurrent) of diarrhea associated with excretion of any ETEC, irrespective of phenotype, and no other copathogen.
    Time Frame
    365-day period starting 14 days after the third vaccination
    Title
    IgG seroconversion
    Description
    IgG seroconversion (≥ twofold increase in post-vaccination endpoint titer over baseline) against rCTB and vaccine-specific colonization factors CFA/I, CS2, CS4
    Time Frame
    Baseline serum specimen is collected before first dose and post-vaccination specimen collected 14 days after third dose
    Title
    IgA seroconversion
    Description
    IgA seroconversion (≥ twofold increase in post-vaccination endpoint titer over baseline) against rCTB and selected vaccine-specific colonization factors CFA/I, CS2, CS4
    Time Frame
    Baseline serum specimen is collected before first dose and post-vaccination specimen collected 14 days after third dose
    Title
    Number of solicited adverse events
    Description
    (i.e., diarrhea, vomiting, fever by caregiver report, poor feeding, and irritability)
    Time Frame
    3-day period after each dose

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    6 Months
    Maximum Age & Unit of Time
    18 Months
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Stephen Savarino, MD, MPH
    Organizational Affiliation
    Naval Medical Research Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs