Gastroenteritis Escherichia Coli Clinical Trial
Official title:
Phase I Study to Determine the Safety and Immunogenicity of an Oral ETEC Candidate Vaccine, Attenuated, Recombinant Double Mutant Heat-Labile Toxin (dmLT) From Enterotoxigenic Escherichia Coli
The purpose of this study is to learn if a new candidate vaccine (dmLT) against ETEC (E. coli infection) is safe. This vaccine will be tested to see what effects it has on the body and the ability of the vaccine to help the body resist disease. Researchers want to find the highest dose of dmLT vaccine that can be given without causing severe side effects. Most E. coli bacteria are harmless to humans and can even be beneficial. However, some are harmful, and can cause diarrhea. About 32 healthy adults, ages 18-45, will participate in this study. This study will require volunteers to stay in the research facility for several nights. 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.
Despite the public health burden of enterotoxigenic Escherichia (E.) coli (ETEC) on travelers, deployed soldiers and, most significantly, young children in the developing world, there is no licensed vaccine against ETEC enteritis. The rationale for using an E. coli heat labile enterotoxin (LT) (R192G/L211A) vaccine, also called double-mutant LT (dmLT), is that it is expected to be especially well tolerated by subjects. If dmLT is safe and immunogenic, it may become an anti-toxin vaccine or a component of other ETEC vaccine candidates, as well as an adjuvant for mucosal immunization. This is a phase I dose escalation study, in which 4 cohorts of 6 subjects each will be enrolled and receive 5 micrograms (mcg), 25 mcg, 50 mcg, or 100 mcg of dmLT vaccine, plus a fifth cohort of 12 subjects which will be randomized and double-blinded to receive either 50 mcg or 100 mcg of dmLT vaccine. A Safety Monitoring Committee (SMC) will be convened for this study, and will review available safety data through the Day 8 visit for each cohort prior to making a recommendation to the Sponsor on whether or not to proceed to the next cohort. If a dose is not well tolerated as determined by the SMC review of the safety data, a Confirmation Cohort of 8 subjects will be enrolled and administered the previous dose. The first two cohorts will be enrolled simultaneously, dosed with investigational product, and observed to ensure the tolerability through Day 8 of the 5 mcg and 25 mcg dose levels. The first two cohorts will be dosed simultaneously based on the excellent safety record of these doses for the single mutant LT (LTR192G). Thereafter, dose escalation and subject enrollment will proceed in a step-wise fashion. 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 are the rate and titer of seroconversion with serum and fecal immunoglobulin A (IgA) anti-LT antibodies measured by ELISA and stimulation of anti-LT antibody secreting cells (ASC). The sample size was chosen based on the exploratory nature of this test article study that has not previously been given to humans. Participants will include 36 healthy adult male and female subjects, ages 18 to 45 inclusive. The primary objective of this study is to assess the safety of dmLT vaccine when administered as a single oral dose over a range of dose levels in healthy adult subjects. The primary objective of Cohort 5 will be to evaluate the safety and immunogenicity of the 50 µg and 100 µg doses of an orally administered dmLT vaccine in healthy adult subjects. The secondary objectives are to assess long-term safety follow-up from immunization through Month 6 post vaccination and to evaluate the immunogenicity of a single oral dose of dmLT vaccine over a range of doses in healthy adult subjects. ;
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
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