Safety and Efficacy Study of CVD 1208S, a Live, Attenuated Oral Vaccine to Prevent Shigella Infection: Phase IIa
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|ClinicalTrials.gov Identifier: NCT00866476|
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, a Shigella flexneri 2a live, oral vaccine Other: Placebo||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:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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 IIa Vaccination Study|
|Study Start Date :||January 2010|
|Actual Primary Completion Date :||February 2010|
|Actual Study Completion Date :||February 2010|
Biological: CVD 1208S, a Shigella flexneri 2a live, oral vaccine
CVD 1208S consists of freshly harvested ∆guaBA, ∆sen, ∆set S. flexneri 2a strain 2457T suspended in phosphate buffered saline to reach the desired inoculum Form: liquid Dose: 10 to the 9th power CFU in 1.0 ml Route: oral.
|Placebo Comparator: Placebo||
30 ml of buffer solution (2.0 grams of NaHCO3 dissolved in 150 ml of sterile water) without bacteria, to which food grade corn starch, USP is added, as necessary, to match the turbidity of the vaccine inoculum
- To evaluate, in healthy volunteers, the safety and clinical acceptability of three spaced doses (one month apart) of CVD 1208S vaccine candidate, with particular attention to the occurrence of diarrhea, dysentery, and fever [ Time Frame: approximately June 2009-January 2010 and October 2010 ]
- To characterize the following immune responses following ingestion of this vaccine: Serum IgA and IgG anti-S. flexneri 2a lipopolysaccharide (LPS) antibody and IgA anti-LPS antibody secreting cells (ASC) [ Time Frame: approximately June 2009, February 2010 - April 2010, and October 2010 ]
- To assess the fecal shedding of CVD 1208S [ Time Frame: approximately June - July 2009 and October 2010 ]
- To elucidate the systemic and mucosal immune responses to vaccination, including fecal IgA antibodies to LPS and Ipas, IgG anti-LPS ASCs, IgG and IgA Ipa ASC, ASC & T cell homing, specific B and T memory responses, and cytokine production by PBMC. [ Time Frame: approximately June 2009 and August - 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): NCT00866476
|United States, Maryland|
|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|