Clinical Trial: Safety and Efficacy Study of WRSS1, a Shigella Sonnei Vaccine Candidate

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Safety, Immunogenicity, and Efficacy Studies of WRSS1, a Live Attenuated Shigella Sonnei Vaccine Candidate, in Healthy Thai Adults

Brief Summary:

This study is an inpatient trial to determine the safety, immunogenicity and efficacy of the WRSS1 candidate vaccine in healthy Thai adult volunteers. This study is designed as 2 parts.

  • Part 1 is a blinded, placebo-controlled inpatient trial in a total of 20 volunteers (14 vaccinees and 6 controls) to determine the safety and immunogenicity. Volunteers will be vaccinated with a single oral dose of 104 colony forming unit (cfu) of WRSS1 or placebo given with bicarbonate buffer.
  • Part 2 will be started approximately 60 days after WRSS1 vaccination. This part is an inpatient phase II efficacy trial involving a challenge with the S.sonnei 53G of 10 vaccinees from the first part and 10 naïve controls.

Detailed Summary:
Sponsor: U.S. Army Medical Research and Materiel Command

Current Primary Outcome:

  • Number and frequency of adverse events. [ Time Frame: Up to 12 months ]
    Frequency of any mild, moderate, and severe signs and symptoms associated with the vaccine such as nausea, vomiting, diarrhea, dysentery, fever, abdominal cramping, and dehydration, as well as any unexpected events. Frequency of significant clinical laboratory abnormalities
  • Immunogenicity [ Time Frame: Days 0,3,5,7,9,14, and 28 ]

    Study Part 1:

    Frequency and increase in antigen-specific serum IgG, IgA, and IgM antibody titers to S. sonnei LPS and invaplex-protein antigens. Frequency and increase in antigen-specific fecal IgA antibody titer to S. sonnei LPS and invaplex-protein antigens (study day -1 or 0, study days 3,5,7,14, and 28). Frequency and increase in antigen-specific IgG, IgA, and IgM antibody secreting cells (ASC) and antibody titers in lymphocyte supernatant (ALS) to S. sonnei LPS and invaplex-protein antigens (study days 0,7, and 9).

  • Efficacy [ Time Frame: Days 0-5 ]
    Study Part 2-Frequency of Shigella induced clinical disease defined as one or more of diarrhea, dysentery or fever in vaccinees and controls following challenge with S. sonnei 53G


Original Primary Outcome:

  • Safety/Clinical tolerance [ Time Frame: Study Parts 1,2-Daily, days 0-13; day 14, 28, and 60 ]
    Frequency of any mild, moderate, and severe signs and symptoms associated with the vaccine such as nausea, vomiting, diarrhea, dysentery, fever, abdominal cramping, and dehydration, as well as any unexpected events. Frequency of significant clinical laboratory abnormalities
  • Immunogenicity [ Time Frame: Parts 1,2-Study days 0,14, and 28 ]
    Frequency and increase in antigen-specific serum IgG, IgA, and IgM antibody titers to S. sonnei LPS and invaplex-protein antigens. Frequency and increase in antigen-specific fecal IgA antibody titer to S. sonnei LPS and invaplex-protein antigens. Frequency and increase in antigen-specific IgG, IgA, and IgM antibody secreting cells (ASC) and antibody titers in lymphocyte supernatant (ALS) to S. sonnei LPS and invaplex-protein antigens.
  • Efficacy [ Time Frame: Daily, Study days 0-5, 14, 28, 60 ]
    Study Part 2-Frequency of Shigella induced clinical disease defined as one or more of diarrhea, dysentery or fever in vaccinees and controls following challenge with S. sonnei 53G


Current Secondary Outcome:

  • Fecal shedding of vaccine [ Time Frame: Days 0-13 ]

    Study Part 1:

    Frequency and duration of detectable fecal presence of WRSS1 by PCR and culture

  • Transmissibility of WRSS1 to placebo recipients [ Time Frame: Days 0-13 ]

    Study Part 1:

    Frequency of detectable fecal presence of WRSS1 in placebo recipients by PCR and culture

  • Change in clinical laboratory values [ Time Frame: Days 0,7,14, and 28 ]

    Study Part 1:

    Frequency of clinical laboratory changes, both normal and abnormal.



Original Secondary Outcome:

  • Fecal shedding of vaccine [ Time Frame: Daily ]
    Frequency and duration of detectable fecal presence of WRSS1 by PCR and culture
  • Transmissibility of WRSS1 to placebo recipients [ Time Frame: Daily ]
    Frequency of detectable fecal presence of WRSS1 in placebo recipients by PCR and culture
  • Change in clinical laboratory values [ Time Frame: Daily ]
    Frequency of clinical laboratory changes, both normal and abnormal.


Information By: U.S. Army Medical Research and Materiel Command

Dates:
Date Received: December 23, 2009
Date Started: May 2010
Date Completion:
Last Updated: June 2, 2015
Last Verified: June 2015