Dose-Finding Study of CS19 Expressing ETEC Challenge Strains
Recruitment status was Recruiting
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Screening
|Official Title:||Strain and Dose-Finding Study of DS26-1 and WS0115A Enterotoxigenic E. Coli (ETEC) Challenge Strains That Express CS19 Fimbriae|
- Develop of diarrhea. [ Time Frame: 120 hours after challenge ]
- Development of moderate to severe diarrhea [ Time Frame: 120 hours after challenge ]
|Study Start Date:||September 2007|
|Estimated Study Completion Date:||May 2008|
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%.
Other: CS19 expressing ETEC strain
Wild type ETEC strain expressing the colonization faction CS19, and LT and ST enterotoxins.
This is a phase 1, open-label, strain and dose-finding study designed to establish a human challenge modelfor CS19-ETEC that causes a > 80% attack rate without causing high output diarrhea. This study design is identical to that of the CS17 challenge model recently completed. Two strains of CS19-ETEC isolated from human diarrheal cases have been identified and characterized. Each clinical isolate was used to generate a cGMP MCB and procedures were established to create a fresh inoculum to administer orally in a sodium bicarbonate solution for challenge. Refer to Section 8 for full details on the isolation and preparation of these strains.
CS19-ETEC strain WS0115A (toxin phenotype of LT+ ST+ and serotype O114:H-) will be the lead strain and will be administered orally to an initial cohort of 5 subjects. This strain was isolated from the stool of a 12-month-old Egyptian girl suffering from watery diarrhea identified during a surveillance study conducted in Abees, Egypt from 1993 to 1995 by investigators at the Naval Medical Research Unit-3 (NAMRU-3), Cairo, Egypt. A negative microbiologic work-up for copathogens (other bacterialenteropathogens, rotavirus, Giardia lamblia, Entamoeba histolytica, and Cryptosporidium) supports that the isolated WS0115A strain was pathogenic in this child. Since this strain has an LT+ST+ toxin phenotype, it is the preferred strain to lead in testing the challenge model, since heterologous protection by bovine milk IgG anti-CsbD against an LT+ST+ phenotype would offer a more robust test of the protection afforded by anti-colonization. The alternate strain, CS-19 ETEC strain DS26-1 (toxin phenotype LT+ST-;serotype O8:H9) was isolated in 1990 at the U.S. Navy Forward Laboratory from a U.S. soldier with diarrhea while on deployment to Saudi Arabia during Operation Desert Shield. A negative microbiologic work-up for copathogens (Salmonella typhi, Vibrio cholerae, Giardia lamblia or Entamoeba histolytica)supports that the isolated DS26-1 strain was pathogenic in this individual. Each clinical isolate was used to generate a cGMP master cell bank and procedures were established to create a fresh inoculum to administer orally in a sodium bicarbonate solution for challenge. Refer to Section 8 for full details on the isolation and preparation of these strains.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00564863
|Contact: Robin McKenzie, MDfirstname.lastname@example.org|
|Contact: Barbara DeNearing, RNemail@example.com|
|United States, Maryland|
|Center for Immunization Research - Johns Hopkins Bloomberg School of Public Health||Recruiting|
|Baltimore, Maryland, United States, 21205|
|Contact: Robin McKenzie, MD 410-614-1624 firstname.lastname@example.org|
|Contact: Barbara DeNearing, RN 410-502-3337 email@example.com|
|General Clinical Research Center of the Johns Hopkins Hospital||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Robin McKenzie, MD 410-502-1624 firstname.lastname@example.org|
|Contact: Barbara DeNearing, Rn 410-502-3337 email@example.com|
|Principal Investigator:||Robin McKenzie, M.D.||Johns Hopkins Bloomberg School of Public Health|