Dose-Finding Study of CS19 Expressing ETEC Challenge Strains
|Study Design:||Intervention Model: Single Group Assignment
Intervention Model Description:
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.Masking: None (Open Label)
Primary Purpose: Other
|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 ]
|Actual Study Start Date:||September 2007|
|Study Completion Date:||September 4, 2008|
|Primary Completion Date:||May 2008 (Final data collection date for primary outcome measure)|
CS19 expressing ETEC strain
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
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
|United States, Maryland|
|Center for Immunization Research - Johns Hopkins Bloomberg School of Public Health|
|Baltimore, Maryland, United States, 21205|
|General Clinical Research Center of the Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Robin McKenzie, M.D.||Johns Hopkins Bloomberg School of Public Health|