The purpose of this study is to evaluate the efficacy of the oral, live, attenuated ShigETEC vaccine against challenge with S. flexneri 2457T.
In Stage 1 of this study, ShigETEC vaccine or placebo will be administered orally to healthy participants at a dose of 5x10\^10 CFU. This dose was tested in a Phase 1 trial and found to be safe when given 4 times with an interval of 3 days between each dose.
The efficacy of ShigETEC vaccination will be evaluated in Stage 2 of this study, when participants will be challenged with S. flexneri 2457T.
The study population will be healthy adult participants in the age of 18-50 years (inclusive), which are clearly defined in the study protocol.
Generally healthy non-pregnant, non-nursing adults aged 18 to 50 years.
Who are determined by medical history, physical examination, laboratory testing, and clinical judgment to be eligible for this study.
Who provide written informed consent after the nature of the study had been explained.
Who are available for the duration of the trial (from enrollment to study completion).
Participants who are perceived to be unavailable or difficult to contact for evaluation or study visits during the study period.
Presence of a significant medical or psychiatric condition which in the opinion of the Investigator precludes participation in the study.
Clinically significant abnormalities in screening hematology or serum chemistry, defined as > grade 1 abnormality of serum potassium, alanine aminotransferase (ALT) or creatinine, hemoglobin, white blood cell count (WBC), or neutrophil count.
Who have received any blood products, including immunoglobulin, in the period from 6 months prior to vaccination or are anticipated to receive such products through to the conclusion of the study and have not donated blood within 30 days and agree not to donate blood until 1 year after challenge.
Parallel
ShigETEC vaccine
Biological/VaccineThe ShigETEC vaccine will be administered orally 4 times at 3-day intervals as a bacterial suspension in a volume of 30 mL per dose (target to contain 5x10\^10 CFU)
Placebo
Other interventionEligible participants will be randomly assigned in a 1:1 ratio to receive either ShigETEC 5x10\^10 colony forming units (CFU) or placebo. Participants will receive their assigned treatment on Days 1, 4, 7, and 10.
Challenge: Shigella flexneri 2457T at a dose of 1.5x10^3 CFU
Biological/VaccineIn the challenge stage all participants will receive 1 oral dose of Shigella flexneri 2457T at a dose of 1.5x10\^3 CFU.
Efficacy of the ShigETEC vaccine in preventing shigellosis caused by the challenge strain
The proportion of participants with incidence of shigellosis caused by the challenge strain in vaccine vs. placebo recipients until the start of antibiotic administration.
Safety and tolerability of ShigETEC oral vaccine
* Number and severity of gastrointestinal and other solicited symptoms (specified as reactogenicity events) up to Day 16 (6 days after last vaccination) * Number and severity of unsolicited AEs up to Day 60 (28 days after challenge) * Number and severity of SAEs/MAAEs/pIMD up to Day 375 (12 months after last vaccination) * Number and severity of AEs of special interest
Characterization of the challenge strain shedding in stool samples
Number and percentage of participants with detectable presence of challenge strain in stool samples detected by quantitative or qualitative culture or polymerase chain reaction (PCR).
Severity of disease following challenge using Shigella disease score
Maximum disease severity following challenge in the vaccinated vs placebo groups using the Shigella disease score.
Click on the lead sponsor to view all of their trials.
