Safety and Efficacy Challenge Study of CVD 1208S, a Live, Attenuated Oral Vaccine to Prevent Shigella: Phase IIb
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|ClinicalTrials.gov Identifier: NCT00866242|
Recruitment Status : Terminated (Reactogenicity met study halting criteria)
First Posted : March 20, 2009
Last Update Posted : April 21, 2017
|Condition or disease||Intervention/treatment||Phase|
|Shigella||Biological: CVD 1208S, Challenge strain of wild-type Shigella flexneri 2a||Phase 2|
The study comprises a Phase 2 vaccination study and a Phase 2b challenge study. The primary objectives of the Phase 2 vaccination study are: 1. To evaluate, in healthy volunteers, the safety and clinical acceptability of three spaced doses (one month apart) of an investigational, live, oral, attenuated vaccine called CVD 1208S, with particular attention to the occurence of diarrhea, dysentery, and fever, and 2. To characterize immune responses following ingestion of this vaccine. The primary objective of the Phase 2b challenge study is to measure the protective efficacy of 3 spaced doses of vaccine after ingestion of an oral challenge strain called Shigella flexneri 2a strain 2457T.
Shigella is a leading cause of disease and death among children younger than 5 years living in developing countries. The difficulty controlling this infection has led experts to believe that prevention with the use of a vaccine is a promising strategy. At the CVD, we have pursued an approach of developing an oral, attenuated Shigella vaccine that prevents infection with the Shigella types of greatest clinical and epidemiologic importance. One of the strains to be included in the vaccine is called Shigella flexneri 2a. Investigators at the CVD have created a vaccine from Shigella flexneri 2a, designated CVD 1208S, using molecular biology techniques. To date, nearly 40 subjects have received varying doses of this vaccine with good clinical tolerance and modest immunogenicity. Previously a single dose of vaccine was used. In the current study, we will administer doses of vaccine on days 0, 28, and 56 to attempt to maximize immunogenicity. Approximately one month after the 3rd dose, a group of ~15-20 vaccinated volunteers along with a similar number of unvaccinated control subjects will be admitted to the CVD Research Isolation Ward at SNBL and challenged with wild type Shigella flexneri 2a. By comparing the attack rate of illness in vaccinated vs. unvaccinated subjects, we will determine the vaccine's ability to confer protective immunity.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety, Immunogenicity, and Efficacy Following Experimental Challenge of CVD 1208S, a Delta guaBA, Delta Sen, Delta Set Shigella Flexneri 2a Live, Oral Vaccine: Phase IIb Challenge Study|
|Study Start Date :||January 2010|
|Primary Completion Date :||February 2010|
|Study Completion Date :||February 2010|
Biological: CVD 1208S, Challenge strain of wild-type Shigella flexneri 2a
The challenge strain consists of freshly harvested Shigella flexneri 2a strain 2457T diluted in phosphate buffered saline to reach the desired inoculum Form: liquid Dose 10 to the 3rd power CFU in 1.0 ml Route: oral.
- To measure the protective efficacy of 3 spaced doses of vaccine against experimental challenge with wild type S. flexneri 2a 2457T [ Time Frame: approximately October 2010 ]
- To assess the fecal shedding of wild type S. flexneri 2a in vaccinees and controls following challenge [ Time Frame: approximately October 2010 ]
- To elucidate the systemic and mucosal immune responses in vaccinees and control subjects following challenge with wild type S. flexneri 2a [ Time Frame: approximately October 2009, January 2010, and August - October 2010 ]
- To examine which immune responses correlate with protection against experimental challenge [ Time Frame: approximately October 2010 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00866242
|United States, Maryland|
|Shin Nippon Biomedical Laboratories (SNBL) Inpatient Facility|
|Baltimore, Maryland, United States, 21201|
|University of Maryland, Baltimore Center for Vaccine Development|
|Baltimore, Maryland, United States, 21201|
|Principal Investigator:||Karen L Kotloff, M.D.||University of Maryland, Baltimore Center for Vaccine Development|