SF2a-TT15 Conjugate Vaccine in Healthy Adult Volunteers

Study Overview
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Brief Summary
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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
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Subjects will be assigned to one of two cohorts. Cohort 1 will receive the lower dose of 2 μg vaccine (with or without alum adjuvant) or matching placebo. 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.

Official Title
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A Phase I Dose Escalation Study to Assess the Safety and Immunogenicity of the SF2a-TT15 Conjugate Vaccine Against S. Flexneri 2a in Healthy Adult Volunteers

Conditions
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Shigellosis, Bacillary Dysentery

Intervention / Treatment
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* Biological: SF2a-TT15 vaccine
* Biological: SF2a-TT15 vaccine + adjuvant
* Biological: Placebo
* Biological: Placebo + adjuvant


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vaccine dose 1<br>SF2a-TT15 vaccine, 2 μg | Biological: SF2a-TT15 vaccine<br> <br> |
| Experimental: vaccine dose 1+ adjuvant<br>SF2a-TT15 vaccine, 2 μg + alum | Biological: SF2a-TT15 vaccine + adjuvant<br> <br> |
| Experimental: vaccine dose 2<br>SF2a-TT15 vaccine, 10 μg | Biological: SF2a-TT15 vaccine<br> <br> |
| Experimental: vaccine dose 2 + adjuvant<br>SF2a-TT15 vaccine, 10 μg + alum | Biological: SF2a-TT15 vaccine + adjuvant<br> <br> |
| Placebo Comparator: Placebo<br>Tris buffer | Biological: Placebo<br> <br> |
| Placebo Comparator: Placebo + adjuvant<br>Tris buffer + Alum | Biological: Placebo + adjuvant<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event | 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. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity - humoral Immune response | 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 | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, conjugate vaccine, Shigella flexneri 2a, safety, Immunogenicity, Healthy adults