Dose-Finding Study of WS6788A and LSN03-016011/A Enterotoxigenic E. Coli ETEC Challenge Strains That Express CS17

NCT00564577 | Completed Phase 1

• 1 other identifier: CIR 193 (B)
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This will be a strain and dose-finding study in which LSN03-016011/A ETEC will be administered at a starting inoculum of 5x108 cfu to 5 subjects to establish a human disease model. If 80% attack rate (AR) is achieved without high output diarrhea, the same inoculum will be given to 10 more subjects for confirmation of AR. If 80% AR is not achieved, attack rate and severity of disease will be evaluated to determine if the dose should be increased. The same sequence may be conducted with WS6788A if applicable. If the LSN strain causes high output diarrhea the dose will be adjusted down and further dose characterization continued. An iterative process will be used to select the optimal strain and dose with each step reviewed and approved by the medical monitor.

Conditions

Travelers' Diarrhea

Keywords

Diarrhea ETEC

Outcome Measures

Primary Outcomes (1)

• Development of diarrhea

  120 hours after challenge

Secondary Outcomes (1)

• Development of moderate to severe diarrhea

  120 hours after challenge

Study Arms (1)

CFA/I and CS17 challenge strain

OTHER

Colonization factor antigen (CFA/I) and CS17 challenge strainAscending dose finding study in 5-10 subjects per dose; to identify the dose able to give a diarrheal attack rate greater than or equal to 80%.

Biological: CFA/I and CS17 challenge strain

Interventions

CFA/I and CS17 challenge strain BIOLOGICAL

Wild type ETEC strain expressing the colonization factor CS17, and heat labile (LT) enterotoxin

Also known as: Experimental

CFA/I and CS17 challenge strain

Eligibility Criteria

• Age: 15 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female between 18 and 45 years of age, inclusive.
• General good health, without significant medical illness, abnormal physical examination findings or clinical laboratory abnormalities as determined by principal investigator or principal investigator in consultation with the medical monitor and sponsor.
• Demonstrate comprehension of the protocol procedures and knowledge of ETEC illness by passing a written examination (pass grade ≥ 70%)
• Willing to participate after informed consent obtained.
• Available for all planned follow-up visits.
• Negative serum pregnancy test at screening and a negative urine pregnancy test on the day of admittance to the inpatient phase for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female subjects unable to bear children must have this documented (e.g., tubal ligation or hysterectomy).

You may not qualify if:

• Presence of a significant medical condition, (e.g. psychiatric conditions or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease, alcohol or illicit drug abuse/dependency), or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.
• Immunosuppressive illness or immunoglobulin A (IgA) deficiency (below the normal limits)
• Positive serology results for HIV, HBsAg, or Hepatitis C virus (HCV) antibodies.
• Significant abnormalities in screening lab hematology, serum chemistry, urinalysis or EKG (EKG in subjects ≥ 40 years), as determined by PI or PI in consultation with the medical monitor and sponsor.
• Allergy to fluoroquinolones, trimethoprim-sulfamethoxazole, or ampicillin/penicillin (excluded if allergic to two of three).
• Fewer than 3 stools per week or more than 3 stools per day as the usual frequency, loose or liquid stools other than on an occasional basis.
• History of diarrhea in the 2 weeks prior to planned inpatient phase
• Regular use of laxatives or any agent that increase gastric pH (regular defined as at least weekly).
• Use of antibiotics during the 7 days before bacterial dosing or proton pump inhibitors, H2 blockers, or antacids within 48 hours of dosing.
• Travel to countries where ETEC or cholera infection is endemic (most of the developing world) within two years prior to dosing.
• History of vaccination for or ingestion of ETEC, cholera, or LT toxin.
• Stool culture (collected no more than 1 week prior to admission) positive for CS17 + ETEC or other bacterial enteric pathogens (Salmonella, Shigella and Campylobacter).
• Use of any investigational product within 30 days preceding the receipt of the challenge inoculum, or planned use during the active study period.
• Use of any medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding receipt of the challenge inoculum or planned use during the active study period.

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• Naval Medical Research Center: collaborator

Study Sites (2)

Center for Immunization Research - Johns Hopkins Bloomberg School of Public Health

Baltimore, Maryland, 21205, United States

Location

General Clinical Research Center of the Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Study Officials

• Robin McKenzie, M.D.

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2007
• First Posted: November 28, 2007
• Study Start: September 1, 2006
• Primary Completion: June 13, 2007
• Study Completion: June 13, 2007
• Last Updated: April 11, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)