NCT02773446

Brief Summary

The purpose of this study is to determine the safe and optimal dose and regimen (fasting duration) for administering the challenge ETEC strain B7A, a CS6 expressing ETEC strain. Additionally, an assessment of homologous protection following rechallenge with B7A will be assessed.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
47

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Apr 2016

Shorter than P25 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2016

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

May 10, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

May 16, 2016

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

July 6, 2018

Completed
Last Updated

July 6, 2018

Status Verified

April 1, 2018

Enrollment Period

8 months

First QC Date

May 10, 2016

Results QC Date

November 29, 2017

Last Update Submit

June 6, 2018

Conditions

Healthy Volunteer

Keywords

ETECEscherichia colienteritisChallengeCS6Enterotoxigenic

Outcome Measures

Primary Outcomes (4)

  • Number of Participants With Safety- Solicited Symptoms Related to Challenge Administration

    Solicited symptoms (vomiting, abdominal pain, bloating, lightheadedness, anorexia, generalized myalgia, arthralgias, abdominal cramping, constipation, nausea, malaise, headache, flatulence)

    6 days post-challenge

  • Moderate-severe Diarrhea

    Moderate-severe diarrhea post challenge defined as * moderate diarrhea: 4 to 5 loose/liquid stools or 401-800 of loose/liquid stool in any 24-hour period * Severe diarrhea greater than or equal to 6 loose/liquid stools or greater than 800 g of loose/liquid stools in any 24-hour period

    5 days post challenge (Cohort 1 and Cohort 2 group B) 7 days post challenge (Cohort 2 Group A)

  • Moderate-severe Diarrhea in Subjects Receiving Homologous Rechallenge

    Moderate-severe diarrhea post-challenge defined as * Moderate diarrhea: 4 to 5 loose/liquid stools or 401-800g of loose/liquid stool in any 24- hour period * Severe diarrhea: greater than or equal to 6 loose/liquid stools or greater than 800 g of loose/liquid stool in any 24-hour period

    7 days post-challenge

  • Number of Participants With Safety -Solicited Symptoms Unrelated to Challenge Administration

    Safety solicited symptoms unrelated to challenge administration (vomiting, abdominal pain, bloating, lightheadedness, anorexia, generalized myalgia, arthralgias, abdominal cramping, constipation, nausea, malaise, headache, flatulence)

    6 days post-challenge

Secondary Outcomes (2)

  • Immune Response to Challenge (Serology)

    28 days post challenge

  • Immune Response to Challenge

    6 days post challenge

Study Arms (6)

Cohort 1 group A

EXPERIMENTAL

Volunteers will receive 8 logs of E. coli strain B7A after overnight fast

Biological: ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer

Cohort 1 group B

EXPERIMENTAL

Volunteers will receive 9 logs of E. coli strain B7A after 90 minute fast

Biological: ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer

Cohort 1 group C

EXPERIMENTAL

Volunteers will receive 9 logs of E. coli strain B7A after overnight fast

Biological: ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer

Cohort 1 group D

EXPERIMENTAL

Volunteers will receive 10 logs of E. coli strain B7A after 90 minute fast

Biological: ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer

Cohort 2 group A

EXPERIMENTAL

subjects from Cohort 1 who met primary endpoint will receive optimal regimen as determined by analysis after Cohort 1.

Biological: ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer

Cohort 2 group B

EXPERIMENTAL

Naive subjects who will receive optimal regimen as determined by analysis after Cohort 1

Biological: ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in Buffer

Interventions

ETEC strain B7A (O148:H28 CS6+ LT+ST+) (Lot 0481) in BufferBIOLOGICAL

ETEC Bacteria

Cohort 1 group ACohort 1 group BCohort 1 group CCohort 1 group DCohort 2 group ACohort 2 group B

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Male or female between 18 and 50 years of age, inclusive.
  • General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of the PI.
  • Completion of a training session and demonstration of comprehension of the protocol procedures and knowledge of ETEC-associated illness by passing a written examination.
  • Willingness to participate after informed consent obtained.
  • Availability for the study duration, including all planned follow-up visits.
  • Negative pregnancy test with understanding to not become pregnant during the study or within three months following last scheduled study visit.

You may not qualify if:

  • Presence of a significant medical condition which in the opinion of the investigator precludes participation in the study.
  • Significant abnormalities in screening hematology or serum chemistry as determined by PI or PI in consultation with the research monitor and sponsor.
  • Evidence of confirmed infection with HIV, Hepatitis B, or Hepatitis C.
  • Evidence of Immunoglobulin A (IgA) deficiency (serum IgA \< 7 mg/dL or below the limit of detection of assay).
  • Evidence of current excessive alcohol consumption or drug dependence (a targeted drug screen may be used to evaluate at the clinician's discretion).
  • Evidence of impaired immune function.
  • Recent vaccination or receipt of an investigational product (within 30 days before receipt of challenge).
  • Any other criteria which, in the investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study.
  • History of microbiologically confirmed ETEC or cholera infection in last 3 years.
  • Occupation involving handling of ETEC or Vibrio cholerae currently, or in the past 3 years.
  • Symptoms consistent with Travelers' Diarrhea concurrent with travel or planned travel to countries where ETEC infection is endemic.
  • Vaccination for or ingestion of ETEC, cholera, or E coli heat labile toxin within 3 years prior to dosing.
  • Any prior experimental infection with ETEC strain B7A.
  • Abnormal stool pattern.
  • Regular use of laxatives, antacids, or other agents to lower stomach acidity.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Johns Hopkins Center for Immunization Research

Baltimore, Maryland, 21205, United States

Location

Related Publications (9)

  • Porter CK, Riddle MS, Alcala AN, Sack DA, Harro C, Chakraborty S, Gutierrez RL, Savarino SJ, Darsley M, McKenzie R, DeNearing B, Steinsland H, Tribble DR, Bourgeois AL. An Evidenced-Based Scale of Disease Severity following Human Challenge with Enteroxigenic Escherichia coli. PLoS One. 2016 Mar 3;11(3):e0149358. doi: 10.1371/journal.pone.0149358. eCollection 2016.

    PMID: 26938983BACKGROUND

  • Harro C, Chakraborty S, Feller A, DeNearing B, Cage A, Ram M, Lundgren A, Svennerholm AM, Bourgeois AL, Walker RI, Sack DA. Refinement of a human challenge model for evaluation of enterotoxigenic Escherichia coli vaccines. Clin Vaccine Immunol. 2011 Oct;18(10):1719-27. doi: 10.1128/CVI.05194-11. Epub 2011 Aug 18.

    PMID: 21852546BACKGROUND

  • Chakraborty S, Harro C, DeNearing B, Ram M, Feller A, Cage A, Bauers N, Bourgeois AL, Walker R, Sack DA. Characterization of Mucosal Immune Responses to Enterotoxigenic Escherichia coli Vaccine Antigens in a Human Challenge Model: Response Profiles after Primary Infection and Homologous Rechallenge with Strain H10407. Clin Vaccine Immunol. 2015 Nov 18;23(1):55-64. doi: 10.1128/CVI.00617-15. Print 2016 Jan.

    PMID: 26581889BACKGROUND

  • Isidean SD, Riddle MS, Savarino SJ, Porter CK. A systematic review of ETEC epidemiology focusing on colonization factor and toxin expression. Vaccine. 2011 Aug 26;29(37):6167-78. doi: 10.1016/j.vaccine.2011.06.084. Epub 2011 Jul 1.

    PMID: 21723899BACKGROUND

  • Ahmed T, Bhuiyan TR, Zaman K, Sinclair D, Qadri F. Vaccines for preventing enterotoxigenic Escherichia coli (ETEC) diarrhoea. Cochrane Database Syst Rev. 2013 Jul 5;2013(7):CD009029. doi: 10.1002/14651858.CD009029.pub2.

    PMID: 23828581BACKGROUND

  • McKenzie R, Porter CK, Cantrell JA, Denearing B, O'Dowd A, Grahek SL, Sincock SA, Woods C, Sebeny P, Sack DA, Tribble DR, Bourgeois AL, Savarino SJ. Volunteer challenge with enterotoxigenic Escherichia coli that express intestinal colonization factor fimbriae CS17 and CS19. J Infect Dis. 2011 Jul 1;204(1):60-4. doi: 10.1093/infdis/jir220.

    PMID: 21628659BACKGROUND

  • Porter CK, Riddle MS, Tribble DR, Louis Bougeois A, McKenzie R, Isidean SD, Sebeny P, Savarino SJ. A systematic review of experimental infections with enterotoxigenic Escherichia coli (ETEC). Vaccine. 2011 Aug 11;29(35):5869-85. doi: 10.1016/j.vaccine.2011.05.021. Epub 2011 May 25.

    PMID: 21616116BACKGROUND

  • Lamberti LM, Bourgeois AL, Fischer Walker CL, Black RE, Sack D. Estimating diarrheal illness and deaths attributable to Shigellae and enterotoxigenic Escherichia coli among older children, adolescents, and adults in South Asia and Africa. PLoS Negl Trop Dis. 2014 Feb 13;8(2):e2705. doi: 10.1371/journal.pntd.0002705. eCollection 2014 Feb.

    PMID: 24551265BACKGROUND

  • Lanata CF, Fischer-Walker CL, Olascoaga AC, Torres CX, Aryee MJ, Black RE; Child Health Epidemiology Reference Group of the World Health Organization and UNICEF. Global causes of diarrheal disease mortality in children <5 years of age: a systematic review. PLoS One. 2013 Sep 4;8(9):e72788. doi: 10.1371/journal.pone.0072788. eCollection 2013.

    PMID: 24023773BACKGROUND

MeSH Terms

Conditions

Escherichia coli InfectionsEnteritis

Condition Hierarchy (Ancestors)

Enterobacteriaceae InfectionsGram-Negative Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsGastroenteritisGastrointestinal DiseasesDigestive System DiseasesIntestinal Diseases

Results Point of Contact

Title
Kawsar Talaat
Organization
Johns Hopkins University
ktalaat@jhu.edu
410-502-9627

Study Officials

  • Kawsar R. Talaat, MD

    Johns Hopkins Bloomberg School of Public Health

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 10, 2016

First Posted

May 16, 2016

Study Start

April 1, 2016

Primary Completion

December 1, 2016

Study Completion

December 1, 2016

Last Updated

July 6, 2018

Results First Posted

July 6, 2018

Record last verified: 2018-04

Data Sharing

IPD Sharing
Will share

Data will be published in Peer reviewed journal

Locations

US(1)