Clinical Trial: Safety Study of Inactivated Shigella Whole Cell Vaccine in Adults

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

Official Title: A Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of an Oral Inactivated Whole Cell Shigella Flexneri 2a Vaccine in Healthy Adult Subjects

Brief Summary: This is a research study about an experimental (investigational) oral inactivated whole cell Shigella flexneri 2a killed vaccine (Sf2aWC). Sf2aWC is a killed vaccine that is being made to prevent disease from Shigella., which causes bloody, watery diarrhea. Infants and children living in developing countries experience the greatest consequences of this disease. The purpose of this study is to find a dose of the vaccine that is safe, tolerable, and develops an immune response. About 82 healthy adults, ages 18-45, will participate in this study. This study will require volunteers to stay in the research facility for several nights for the first dose. Participants in Cohorts 2, 3, and 4 will not be required to stay overnight for the second and third doses. Participants will be assigned to receive 1 of 4 vaccine doses by mouth. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 8 months.

Detailed Summary: Despite the public health burden of Shigella spp. on travelers, deployed soldiers and, most significantly, young children in the developing world, there is no licensed vaccine against Shigella. The rationale for using Shigella flexneri 2a whole cell killed vaccine (Sf2aWC), is that it is expected to be especially well tolerated by subjects. If Sf2aWC is safe and immunogenic, it may be combined with S. sonnei and S. flexneri 3a as the basis of a multivalent vaccine, because these three components should cover up to 80% of shigella infections in developing countries and over 90% in developed countries. This is a single site, Phase 1, double-blind, randomized, placebo-controlled, dose-escalation study in healthy adult subjects. Approximately 82 subjects will be enrolled into four separate cohorts and will be randomized to receive Sf2aWC or placebo. The placebo preparation will be bicarbonate buffer. Cohort 1 subjects will receive a single oral dose of Sf2aWC (2.6±0.8 x 10^8 vp/mL) or placebo. Dosing and 72 hours of supervised post-vaccination safety follow-up will be conducted in the CIR Inpatient Unit. Before enrolling subjects in subsequent cohorts, safety data from the previous Cohort(s) through Study Day 7 will be evaluated and reviewed by the Safety Review Committee (SRC). Cohorts 2, 3, and 4 participants will receive three doses of Sf2aWC vaccine or placebo at 0, 1 and 2 months. The first immunization will be administered in the CIR inpatient unit, followed by 72 hours of direct post-immunization observation. If after review by the SRC the first dose appears safe and well tolerated, subsequent doses will be administered on an outpatient basis. Safety will be assessed by solicited symptoms/subject memory aid and laboratory evaluations. Adverse events (AE)s will be graded according to standardized criteria. The immunogenicity outcome measures of interest include serum IgG and IgA antibodies by ELISA against S. flexneri 2a LPS and S. flexneri 2a invasive protei
Sponsor: PATH

Current Primary Outcome: Safety [ Time Frame: 6 months after the 3rd vaccination ]

Local and systemic reactogenicity will be assessed post-vaccination using targeted physical examinations, vital signs and clinical laboratory tests, and diary cards (to be completed following discharge daily through Day 7). The primary reactogenicity of fever, headache, malaise, and defined symptoms and signs for gastroenteritis and reactive arthritis will be evaluated daily through Day 7. For Cohorts 2, 3, and 4, doses 2 and 3 will be administered on an outpatient basis and daily diary cards will be utilized through Day 7 after each immunization.


Original Primary Outcome: Same as current

Current Secondary Outcome: Immunogenicity [ Time Frame: Baseline through 112 days post-vaccination ]

ALS/ASC assays and measures of T cell response and B cell memory. B cell assays will be carried out with specimens obtained within 24 hours prior to vaccination and 7 days following each vaccination. Cytokine assays will be carried out with specimens obtained prior to initial vaccination and approximately 8, 24, 48, and 72 hours later. Cytokine assays will also be performed using specimens obtained from Cohorts 2, 3, and 4 subjects 2 days following the third vaccination. In Cohorts 2, 3, and 4, B cell memory will be assessed prior to first vaccination and on Day 112.


Original Secondary Outcome: Same as current

Information By: PATH

Dates:
Date Received: January 5, 2012
Date Started: March 2011
Date Completion:
Last Updated: February 4, 2013
Last Verified: January 2012