Bacillary Dysentery, Shigellosis
Conditions
Keywords
Phase I, conjugate vaccine, Shigella flexneri 2a, safety, Immunogenicity, Healthy adults
Brief summary
This is a first-in-human, single-center, single-blinded, observer-masked randomized, dose escalation (two doses), placebo-controlled study in healthy volunteers.
Detailed description
Subjects will be assigned to one of two cohorts. 1. Cohort 1 will receive the lower dose of 2 μg vaccine (with or without alum adjuvant) or matching placebo. 2. Cohort 2 will receive the higher dose of 10 μg vaccine (with or without alum adjuvant) or matching placebo. Eligible subjects will be randomized to receive the 2 μg dose or 10 µg without or with alum or matching placebo, at a ratio of 3:1, as three single IM injections. There will be an interval of 28(±3) days) between each treatment. The study will be conducted in a stepwise approach in which a Pioneer Group of 2 subjects (one receiving the active vaccine and one receiving the matching placebo) will receive the first injection. These subjects will remain in-house for a 24-hours medical observation after the first injection (not required in the subsequent injections) Once it has been established that there are no safety concerns in the non-adjuvanted Pioneer Groups (and after no less than 48 hrs), the next Pioneer group (one subject receiving adjuvanted 2 μg vaccine and one receiving the matching alum placebo) will be injected. If no safety concerns are raised in this group also, after no less than 48 hrs, the rest of the subjects may receive the first injection.
Interventions
BIOLOGICALSF2a-TT15 vaccine
BIOLOGICALSF2a-TT15 vaccine + adjuvant
BIOLOGICALPlacebo
BIOLOGICALPlacebo + adjuvant
Sponsors
Institut Pasteur
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects in general good health in the opinion of the investigator as determined by medical history, vital signs and a physical examination. * Negative human leukocyte antigen (HLA) -B27 and no history of reactive arthritis * Negative HIV, Hepatitis B and Hepatitis C serology tests. * Blood levels of Shigella flexneri 2a LPS IgG antibodies ≤ percentile 80 * No known history of alcohol abuse
Exclusion criteria
* Subjects with a history of clinically significant gastrointestinal disorders or with any history of frequent diarrhea, nausea or emesis, regardless of etiology. * Individuals with immunosuppressive diseases or under immunosuppressive therapy * History of culture-proven S. flexneri. * Individuals who have household contact with/and /or intimate exposure to an individual with laboratory confirmed S. flexneri. * Having travelled in countries/areas highly endemic for S. flexneri within 3 months prior to enrolment. * Previous participation in any study in which a Shigella-vaccine candidate was administered. * Known contraindication, hypersensitivity and/or allergy to the investigational product or its excipients. * Known hypersensitivity and/or allergy to any drug or vaccine * Women who are pregnant or are breast-feeding, or are of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | 12 months | Safety: Occurrence, frequency, severity, and duration of local and systemic adverse events (AEs) including clinically significant laboratory abnormalities, after administration of the SF2a-TT15 vaccine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity - humoral Immune response | 12 months | Serum antibody response (IgG IgM, IgA) to S. flexneri 2a LPS, following the administration of the various vaccine doses and antibody secreting cells to S. flexneri 2a LPS, following the administration of the various vaccine doses |
Countries
Israel
Outcome results
None listed