Study Confirming A Human Challenge Model and Investigating The Safety Of VLA1701

Study Overview
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Brief Summary
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This is a single-center, double-blind, placebo-controlled, Phase II vaccination and challenge study designed to confirm a human challenge model with E. coli strain LSN03-016011/A.

Detailed Description
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This is a single-center, double-blind, placebo-controlled, Phase II vaccination and challenge study designed to confirm a human challenge model with E. coli strain LSN03-016011/A (LT+ (Labile toxin), ST- (Stable toxin), CS17), as well as collect expanded safety and immunogenicity data. The study will be carried out in two phases: Vaccination phase: up to 34 subjects will be randomized 1:1 to receive 2 doses of either VLA1701 or placebo orally. The doses will be given 7 days apart and subjects will be followed as an outpatient for safety. Challenge Phase: 30 Subjects, out of the 34 subjects, will be challenged. After challenge, subjects will be monitored for diarrhea and other signs/symptoms of enteric illness by daily medical checks, vital sign determinations, grading and weighing of all stools.

Official Title
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Randomized Double-Blinded Pilot Study Confirming A Human Challenge Model Using LSN03-016011/A Expressing LT And CS17 And Investigating The Safety Of VLA1701 (An Investigational Oral Cholera And ETEC (Enterotoxigenic E Coli) (Vaccine)

Conditions
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Enterotoxigenic Escherichia Coli Infection, Diarrhea

Intervention / Treatment
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* Biological: VLA1701
* Biological: Placebo
* Other: Challenge Strain


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and non-pregnant female subjects aged 18 to <50 years; BMI of 19.0 to 35.0 kg/m2 Willingness to participate after informed consent has been obtained from the subject prior to any study related procedures. Completion of a training session and demonstration of comprehension of the protocol procedures and knowledge of ETEC-associated illness by passing a written examination. If subject is of childbearing potential: Negative pregnancy test at screening with understanding to not become pregnant within 28 days after challenge; Subject has practiced an effective method of contraception during the 30 days before screening (Visit 0); Subject agrees to employ adequate birth control measures for the duration of the study. Exclusion Criteria Participated in research involving investigational product within 30 days before planned date of first vaccination or planned use through Day 44; Any prior exposure to ETEC (including LSN03-016011/A) or cholera occupationally or received LT (Or any mutant forms of LT (e.g., LTR192G, LTR192GL211A), ETEC, or cholera vaccine); Subjects with known abnormal stooling patterns (fewer than 3 per week or more than 3 per day); Known allergies to any component of the vaccine; Subjects with known allergies to more than 1 planned antibiotics: History of diarrhea while traveling in a developing country within the last 3 years; Subjects whose occupation involves handling of ETEC or cholera bacteria; Women who are pregnant or breastfeeding; Significant medical conditions including chronic, immunosuppressive, malignant, or gastrointestinal diseases (e.g. History of Irritable Bowel Syndrome (as defined by the Rome III criteria or medical diagnosis) or gastric ulcer disease) or enteric, pulmonary, cardiac, liver or renal disease. Some medical conditions which are adequately treated and stable may be acceptable in the study (e.g. hypertension); Significant abnormalities in screening lab hematology or serum chemistries; Use of any medication known to effect the immune system (e.g. systemic corticosteroids) within 30 days of vaccination or planned use during active study period (excluding inhaled steroids); Evidence of confirmed infection with HIV, Hepatitis B or Hepatitis C; Subjects with IgA (Immunoglobulin A) deficiency (serum IgA < 7 mg/dl or limit of detection of assay); Regular use of antacids, antidiarrheal, loperamide, bismuth subsalicylate, diphenoxylate or similar medication less than 2 weeks prior to enrolling in the study and through the inpatient portion of the study; Known or suspected alcohol abuse or illicit drug use within the last year, positive urine toxicology for drugs of abuse; Persons who are committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities); Persons who are in a dependent relationship with the sponsor, an investigator or other study team members, or the study center. 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: 49 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VLA1701<br>VLA1701 is an investigational oral vaccine against LT-ETEC (Labile Toxin-Enterotoxigenic E coli) The vaccine is administered orally in 2 doses about 1 week apart. | Biological: VLA1701<br>* VLA1701 is an investigational oral vaccine against LT-ETEC (Labile Toxin-Enterotoxigenic E coli)<br>Other: Challenge Strain<br>* LSN03-016011/A<br>|
| Placebo Comparator: Placebo<br>The buffer component of VLA1701 will be used as Placebo. The vaccine is administered orally in 2 doses about 1 week apart. | Biological: Placebo<br>* buffer component of VLA1701<br>Other: Challenge Strain<br>* LSN03-016011/A<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Moderate to Severe Diarrhea | within 120 hours of challenge with ETEC strain LSN03-016011/A. | 5 days after challenge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Severity Score After Challenge With ETEC Strain LSN03-016011/ A | ETEC diarrhea disease severity score with a score ranging from 0 (no disease) to 8 (most severe disease) utilizing objective signs, subjective Symptoms and stool output. | 7 days after challenge | 
| Percentage of Subjects With Solicited Adverse Events | adverse events covered by the subjects memory card | 7days after each vaccination | 
| Percentage of Subjects With Any Adverse Events (AE) |  | until Month 6 | 
| Number of Subjects With Serious Adverse Events |  | until Month 6 | 
| Percentage of Subjects With Any IMP (Investigational Medicinal Product) Related Adverse Events | unsolicited events | up to Visit 4 (day of challenge, 23 days post first vaccination) | 
| Percentage of Subjects With IMP-related Serious Adverse Events |  | up to Visit 4 (day of challenge, 23 days post first vaccination) |