Dose-Finding Study of CS19 Expressing ETEC Challenge Strains

NCT00564863 | Completed Phase 1

• 3 other identifiers: CIR 240WIRB Approval Number 20071069Gm 100018
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

This will be a strain and dose-finding study in which CS19-ETEC strain WS0115A will be administered at a starting inoculum of 5 x 108 colony forming units (cfu) to 5 subjects as the initial step to establish a human disease model. If an 80% attack rate (AR) for predefined diarrheal disease is achieved without high output diarrhea, the same inoculum will be given to 5 - 10 more subjects for confirmation of AR. If an 80% AR is not achieved, AR and severity of disease will be evaluated to determine if the dose should be increased. The same sequence may be conducted with DS26-1 as necessary. If the WS0115A 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)

• Develop of diarrhea.

  120 hours after challenge

Secondary Outcomes (1)

• Development of moderate to severe diarrhea

  120 hours after challenge

Study Arms (1)

CS19 expressing ETEC strain

OTHER

Ascending 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: CS19 expressing ETEC strain

Interventions

CS19 expressing ETEC strain BIOLOGICAL

Wild type ETEC strain expressing the colonization faction CS19, and LT and ST enterotoxins.

CS19 expressing ETEC strain

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: 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 (PI) or PI 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 entire inpatient portion of study and all outpatient study visits.
• Negative serum pregnancy test at screening (initial visit and day -7 to - 3) and a negative urine pregnancy test on the day of admission 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. Alternatively, abstinence alone is acceptable. Female subjects who are unable to bear children must provide supporting documentation (e.g., prior 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 IgA deficiency (below the normal limits)
• Positive serology results for HIV, HBsAg, or HCV antibodies.
• Significant abnormalities in screening laboratory hematology, serum chemistry, urinalysis, as determined by PI or PI in consultation with the medical monitor and Sponsor.
• Allergy to fluoroquinolones, cotrimoxazole, 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 increases 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 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) within 30 days preceding receipt of the challenge inoculum or planned use during the active study period. (Topical and intra-articular steroids will not exclude subjects). MANAGEMENT

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

MeSH Terms

Conditions

Diarrhea

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is a phase 1, open-label, strain and dose-finding study designed to establish a human challenge model for CS19-ETEC that causes a \> 80% attack rate without causing high output diarrhea. This will be a strain and dose-finding study in which CS19-ETEC strain WS0115A will be administered at a starting inoculum of 5 x 108 colony forming units (cfu) to 5 subjects as the initial step to establish a human disease model. If an 80% attack rate (AR) for predefined diarrheal disease is achieved without high output diarrhea, the same inoculum will be given to 5 - 10 more subjects for confirmation of AR. If an 80% AR is not achieved, AR and severity of disease will be evaluated to determine if the dose should be increased. The same sequence may be conducted with DS26-1 as necessary.

Study Record Dates

• First Submitted: November 26, 2007
• First Posted: November 28, 2007
• Study Start: September 1, 2007
• Primary Completion: May 1, 2008
• Study Completion: September 4, 2008
• Last Updated: April 5, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)