This Phase 1 clinical trial is aimed to evaluate the safety and immunogenicity of 3 doses of 5 sequentially escalating dosages of a candidate vaccine against Shigella sonnei (1790GAHB vaccine) administered by intramuscular route in healthy adults (18 to 45 years of age at enrollment). The safety profile of the 1790GAHB vaccine is evaluated in comparison to that of placebo (GAHB-Placebo), constituted by an aluminum hydroxide suspension having the same concentration as study vaccine formulations. A total of 50 eligible subjects will be assigned to one of five sequential cohorts of 10 subjects each. Within each cohort, in an observer-blind fashion, subjects will be randomized to receive three vaccinations, four weeks apart, of either 1790GAHB vaccine (at five antigen concentrations) or GAHB placebo. A Data Safety Monitoring Board will be in place to receive a summary of all safety data obtained during one week follow-up post-first vaccination with the lower dose. Based on evaluation of the safety data, the Data Safety Monitoring Board will make a recommendation, as to whether the next cohort should be vaccinated with higher antigen concentration or not. Expected duration of the study for an individual subject is 9 months. Each subject will be followed-up for 6 months after the 3rd vaccination.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
50
Centre d'Investigation Clinique en Vaccinologie Cochin-Pasteur (CIC1417)
Paris, Paris Cedex 14, France
Number of Subjects With Solicited Local Reaction After Any Vaccination
Any erythema/induration refers to: ≥25 mm in diameter. Grade 3 (severe) refers to erythema/induration \>100 mm in diameter. Grade 3 (severe) for injection site pain refers to: prevents daily activity
Time frame: During a 7-day (Days 1-7) post vaccination period following any injection
Number of Subjects With Solicited Systemic Reaction After Any Vaccination
Any= Incidence of any symptom regardless of intensity grade. Grade 3 = symptom that prevented daily activities
Time frame: During a 7-day (Days 1 to 7) post vaccination period following any injection
Number of Subjects With Neutrophils Results Below and Above the Normal Ranges
Day 8: VISIT 2 (D7 post 1st vac)
Time frame: At Day 8
Number of Subjects With Neutrophils Results Below and Above the Normal
Day 36: VISIT 3.1 (D7 post 2nd vac.)
Time frame: At Day 36
Number of Subjects With Neutrophils Results Below and Above the Normal
Day 57: VISIT 4 (3rd vac.)
Time frame: At Day 57
Number of Subjects With Neutrophils Results Below and Above the Normal
Day 64: VISIT 4.1 (D7 post 3rd vac.)
Time frame: At Day 64
Number of Subjects With Neutrophils Results Below and Above the Normal
Day 85: VISIT 5 (1 month post 3rd vac.)
Time frame: At Day 85
Number of Subjects With Neutrophils Results Below and Above the Normal
Day 225: VISIT 6 (6 months post 3rd vac.)
Time frame: At Day 225
Anti-LPS S. Sonnei Serum IgG Geometric Mean Concentration (GMCs)
Time frame: At baseline, at 28 days after each vaccination and at 168 days after last vaccination
Number of Subjects With Seroresponse for Anti-LPS S. Sonnei
Seroresponse is defined as: If half of the baseline value is greater than 25 ELISA Unit (EU) then an increase of at least 50% in the post-vaccination sample as compared to baseline \[i.e. ((Post-vac minus baseline)/baseline)100% ≥ 50%\]. If half of the baseline value is less or equal to 25 EU then an increase of at least 25 EU in the post-vaccination sample as compared to baseline (i.e. \[post-vac minus baseline\] ≥25 EU)
Time frame: At 28 days after each vaccination and 168 days after last vaccination
Number of Subjects With High Seroresponse for Anti-LPS S. Sonnei (IgG ELISA ≥121 EU)
High seroresponse is defined as a post vaccination titer ≥X anti-LPS serum IgG units in the GSK (former Novartis) ELISA that correspond to a titer of 1:800 in the ELISA method used by Cohen et al. To determine the value for 'X' the GSK (former Novartis) anti-LPS ELISA was calibrated against the Cohen ELISA and it was found that a concentration of 121 EU EU/mL corresponds to a titer of 1:800 in the Cohen assay
Time frame: At baseline, at 28 days after each vaccination and at 168 days after last vaccination
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