Phase 2b Challenge Study With the Bioconjugate Vaccine Flexyn2a

Study Overview
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Brief Summary
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In this proof of concept challenge study, the bioconjugate candidate vaccine Flexyn2a will be tested for its ability to induce an immune response that protects healthy adult volunteers from infection with a wild-type Shigella flexneri 2a strain compared to subjects receiving placebo.

Detailed Description
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Flexyn2a is a bioconjugate candidate vaccine that is able to induce an humoral immune response specific for the 2a-antigen of Shigella flexneri 2a bacteria. Healthy adult volunteers naïve for Shigella flexneri 2a infections at screening will receive two administrations of 10 micrograms Flexyn2a or placebo 4 weeks apart. Four weeks after the second vaccination, each subject will be challenged with 1500 cfu of the virulent Shigella flexneri 2a strain 2457T. In order to assess the ability of Flexyn2a to protect against infection with this strain, the attack rate of shigellosis in the group vaccinated with Flexyn2a will be compared to the group of the subjects who received placebo injections.

Official Title
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Phase 2b, Double-blind, Placebo-controlled Efficacy Challenge Study With a Candidate Bioconjugate Vaccine Against Shigella Flexneri 2a

Conditions
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Shigellosis

Intervention / Treatment
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* Biological: Flexyn2a
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age 18-50 years (inclusive) Good health, without clinically significant medical history or physical examination findings. Negative serum pregnancy test at screening, and negative urine before each vaccination and before challenge for female subjects of childbearing potential. Females of childbearing potential must agree to avoid pregnancy by use of effective contraception. Abstinence is not acceptable as effective contraception. Female subjects unable to bear children must have this documented (e.g. tubal ligation or hysterectomy). Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained. Completion of a training session and demonstrated comprehension of the protocol procedures, knowledge of Shigella-associated illness, and a passing score of 70% or better on a written examination. Availability for the study duration, including all planned follow-up visits. Willingness to refrain from participating in other studies of investigational products until completion of the last study visit. Exclusion Criteria: Women currently nursing. 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 as determined by PI or PI in consultation with the research monitor and sponsor. Presence in the serum of HIV antibody, HBs-Ag, or HCV antibody (if confirmed positive by HepC confirmatory test, i.e. RIBA, PCR) Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay). Evidence of current excessive alcohol consumption or drug dependence. Evidence of impaired immune function. BMI <19 and ≥35 Recent vaccination or receipt of an investigational product (within 30 days before vaccination and until last study visit). Personal history of an inflammatory arthritis. Positive blood test for HLA-B27. Personal history of irritable bowel syndrome as defined by Rome III criteria. Treatment with immunoglobulins or blood products within 3 months from first candidate vaccine injection. Regularly abnormal stool pattern (fewer than 3 per week or more than 3 per day) or loose or liquid stools Regular use of laxatives, antacids, or other agents to lower stomach acidity. Use of any medication known to affect the immune function (e.g., systemic steroids) within 30 days preceding the first vaccination or planned use during the entire study period. Known allergy to any of the following antibiotics: ciprofloxacin, trimethoprim-sulfamethoxazole or penicillin. Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where Shigella infection is endemic (most of the developing world) within two years prior to dosing, OR planned travel to endemic countries during the length of the study. Vaccination for or ingestion of Shigella within 3 years prior to vaccination. Use of antibiotics during the 7 days before vaccination and challenge Use of proton pump inhibitors, H2 blockers or antacids within 48 hours prior to challenge. Serum IgG titer to Shigella flexneri 2a LPS ≥ 2500 Current occupation involving handling of Shigella bacteria History of allergy to any vaccine or to soy Any other criteria which, in the investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study

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: Triple


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>* 2 doses of 10 μg of Flexyn2a will be injected intramuscularly 4 weeks apart<br>|
| Placebo Comparator: Placebo<br>2 doses of TBS solution will be injected intramuscularly 4 weeks apart | Biological: Placebo<br>* 2 doses of TBS solution will be injected intramuscularly 4 weeks apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attack Rate of Shigellosis in Vaccinated Subjects. | The attack rate of shigellosis after challenge in vaccine group versus in placebo group was analyzed. | Between Day 56 and Day 64 |