Safety and Tolerability of a Bioconjugate Vaccine Against Shigella Flexneri 2a

Study Overview
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Brief Summary
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This is a phase I, single-blind, randomized, placebo-controlled, single-center study in healthy subjects using a staggered approach to dosing. 30 subjects will be randomized to receive 10 μg Flexyn2a candidate vaccine with or without adjuvant or placebo.

Detailed Description
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A total of 30 subjects will be randomly assigned to one of 3 different arms in order to evaluate the safety, tolerability and immunogenicity of a candidate vaccine, formulated with or without adjuvant, and the outcome compared to a placebo control group. For each active treatment group, 12 subjects will be injected twice with 10 μg Flexyn2a candidate vaccine 4 weeks apart. A control group with 6 subjects will be injected following the same schedule with a placebo solution.

Official Title
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Safety and Tolerability of a Candidate Bioconjugate Vaccine Against Shigella Flexneri 2a When Administered to Adult Volunteers

Conditions
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Shigellosis

Intervention / Treatment
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* Biological: Flexyn2a
* Biological: Placebo
* Biological: Flexyn2a plus adjuvant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female volunteers, age of 18 to 50 years (inclusive) at the time of enrollment. Signed informed consent form. Completion and review of comprehension test (achieved >70% accuracy) Available for the required follow-up period and scheduled clinic visits. Women: negative pregnancy test with understanding (through informed consent process) to not become pregnant or or breastfeed during the study or within twelve (12) weeks after the last vaccine dose. Exclusion Criteria: Health condition that, in the opinion of the investigator, may interfere with optimal participation in the study or place the volunteer at increased risk of adverse Events (AEs). Study clinicians, in consultation with the PI, will use clinical judgment on a case by-case basis to assess safety risks under this criterion. The PI will consult with the Research Monitor as appropriate. Clinically significant abnormalities on physical examination. Clinically significant abnormalities on basic laboratory screening. Presence of significant unexplained laboratory abnormalities that, in the opinion of the PI, may potentially confound the analysis of the study results Regular use of constipation, antacid or anti-diarrheal medications or treatments. Abnormal stool pattern (fewer than 3 stools per week or more than 3 per day) or loose/liquid stools more than occasionally. Use of immunosuppressive drugs such as corticosteroids or chemotherapeutics that may influence antibody development. Women currently nursing. Participation in research involving another investigational product (defined as receipt of investigational product or exposure to invasive investigational device) within 30 days of planned date of first vaccination or anytime throughout the duration of the study. Positive blood test for HBsAg, hepatitis C Virus (HCV), HIV-1. Positive blood test for HLA-B27. Immunosuppressive illness or immunoglobulin deficiency (serum immunoglobulin A level < 7 mg/dL or limit of detection of assay). Family history of congenital or hereditary immunodeficiency. Treatment with immunoglobulins or blood products within 3 months from first candidate vaccine injection. History of microbiologically confirmed Shigella infection. Personal or family history of inflammatory arthritis. Personal or family history of irritable bowel syndrome. Received previous experimental Shigella vaccine or live Shigella challenge. Have had diarrhea while traveling outside the United States or lived for 2 or more months during the past 3 years in a country with potentially higher Shigella infection rates, including Africa, South America, Central America, and Asia (except Japan). Occupation involving handling of Shigella bacteria currently, or in the past 3 years. History of allergy to any vaccine. History of allergy to aluminum hydroxide. Serum immunoglobulin G endpoint titer ≥ 2500 to Shigella Lipopolysaccharide.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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 |
| --- | --- |
| Active Comparator: Flexyn2a<br>2 doses of 10 μg of Flexyn2a will be injected intramuscularly 4 weeks apart | Biological: Flexyn2a<br>* Intramuscular doses of 0.5 mL<br>|
| Active Comparator: Flexyn2a plus adjuvant<br>2 doses of 10 μg of Flexyn2a plus adjuvant will be injected intramuscularly 4 weeks apart | Biological: Flexyn2a plus adjuvant<br>* Intramuscular doses of 0.5 mL<br>|
| Placebo Comparator: Placebo<br>2 doses of saline buffer plus adjuvant will be injected intramuscularly 4 weeks apart | Biological: Placebo<br>* Intramuscular doses of 0.5 mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence and severity of adverse events | Number and severity of local site injection and general adverse events will be collected and compared between the different arms of the study | until Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of antigen-specific antibodies between baseline (D0) and after injection for all groups. | Immunogenicity will be evaluated after the first and second injection and compared to pre-immune levels | until Day 56 | 
| Evaluation of antigen-specific antibodies between subjects receiving the candidate vaccine with and without adjuvant | Immunogenicity will be compared between subjects receiving candidate vaccine with and without adjuvant after the first and second injection | until Day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, bioconjugate vaccine, immunogenicity, shigellosis