Shigella Sonnei Dysenteries Clinical Trial
Official title:
A Phase 2a/2b, Randomized, Double-blinded, Placebo-controlled, Trial to Assess the Safety, Immunogenicity and Efficacy of Inactivated Shigella Flexneri 2a Whole Cell (Sf2aWC) Vaccine Administered With and Without Double Mutant E. Coli Heat Labile Toxin (dmLT) in Healthy Adult Subjects
This is a research study about an experimental (investigational) oral inactivated whole cell Shigella flexneri 2a killed vaccine (Sf2aWC) and an adjuvant called dmLT. Sf2aWC is a killed vaccine that is being made to prevent disease from Shigella., which causes bloody, watery diarrhea. An adjuvant is something that is added to a vaccine to make it work better. The purpose of the study is to see if the vaccine will protect people from Shigella infection with or without an adjuvant called dmLT. About 72 healthy adults, ages 18-45, will participate in this study. The study will compare 2 different vaccination groups and 1 control group. Volunteers have an equal chance to be in any of the 3 groups. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 6 months.
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. This is a single site,
2a/2b, double-blind, randomized, placebo-controlled, study in healthy adult subjects.
Approximately 72 subjects will be enrolled into one of three vaccination groups: Sf2aWC 1011
Sf2aWC cells plus 10 µg dmLT (Group 1, n=24), 1011 Sf2WC cells alone (Group 2, n=24); or
placebo (Group 4, n=24). The placebo preparation will be bicarbonate buffer.
After the vaccination phase subjects will be admitted by cohort on day 84 to an inpatient
facility for 12 days to undergo challenge with approximately 1500 colony forming units (CFU)
of wild type S. flexneri 2a strain 2457T (administered with NaHCO3 buffer). After 5 days of
observation for clinical endpoints (or earlier and within 12 hours if they meet the
definition of moderate-to-severe shigellosis as defined in the primary endpoints section
below), subjects will receive a 5-day course of orally administered ciprofloxacin.
The primary objective of this study are to 1) evaluate, the safety and reactogenicity of 3
oral sequential doses of Sf2aWC with or without dmLT, 2) To measure the protective efficacy
of 3 spaced doses of high-dose Sf2aWC vaccine with and without dmLT against
moderate-to-severe shigellosis following experimental oral challenge with wild-type S.
flexneri 2a 2457T
;