Clinical Trial: Safety and Efficacy Study of CVD 1208S, a Live, Attenuated Oral Vaccine to Prevent Shigella Infection: Phase IIa

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

Brief Summary: The purpose of this study is to determine whether CVD 1208S (a live, attenuated, oral vaccine) is safe and effective in the prevention of Shigella infection.

Detailed Summary:

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 co
Sponsor: University of Maryland

Current Primary Outcome:

  • 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 ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome: Same as current

Information By: University of Maryland

Dates:
Date Received: March 19, 2009
Date Started: January 2010
Date Completion:
Last Updated: April 20, 2017
Last Verified: April 2017