Traveler's Diarrhea (TD) Automated Process

Study Overview
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Brief Summary
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To evaluate and compare the immune responses and safety following a two vaccination regimen by transcutaneous immunization with heat-labile enterotoxin of E. coli (LT) patches or placebo patches.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Immunogenicity and Safety of a Two Vaccination Regimen With an LT Vaccine Patch in Healthy Adults

Conditions
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Prevention of Travelers' Diarrhea

Intervention / Treatment
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* Biological: heat-labile enterotoxin of E. coli (LT)
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult males or females, 18-64 years of age (inclusive) at the planned start of the study (first vaccination on Day 0) Signed Informed Consent Women who are not post-menopausal or surgically sterile must have a negative serum/urine pregnancy test at screening and within 24 hours of each vaccination with understanding (through Informed Consent process) to not become pregnant and to employ an effective form of birth control for the duration of the study. Acceptable forms of birth control are: abstinence, hormonal contraceptives (oral, injectable, implant, patch, ring), double-barrier contraceptives (condom or diaphragm, with spermicide), and IUD. Exclusion Criteria: Laboratory abnormalities [as determined by the Toxicity Grading Scale (grade 1 4)] at laboratory screening Abnormalities at physical examination [as determined by the Toxicity Grading Scale (grade 1-4)] Known allergies to any component of the vaccine Known allergies to adhesives Participated in research involving investigational product within 30 days before planned date of first vaccination or within 90 days after first vaccination Donated blood or blood products such as plasma within 30 days prior to planned date of first vaccination or within 90 days after first vaccination Ever received investigational enterotoxigenic E. coli, LT, or LT (R192G) or NasalFlu, Berna Biotech, Ltd Ever received cholera toxin or vaccine (e.g. Orochol™, Dukoral™) History of diarrhea while traveling in a developing country within the last year History of abdominal surgery (excluding C-section, hysterectomy, cosmetic surgery, liposuction, appendectomy, cholecystectomy, ventral hernia repair, and other surgeries not pertaining to gastrointestinal problems) or history of, or recent acute gastrointestinal illness Positive serology for HIV-1, HIV-2, HBsAg, or HCV Medical history of acute or chronic skin disease at vaccination area(s) Active skin allergy Signs of acute skin infection, sunburn or skin abnormalities at the vaccination area(s) including fungal infections, severe acne, or active contact dermatitis, or a history of keloid formation Excessively hirsute and unwilling to clip hair at the vaccination area(s) Visible tattoos or marks (tattoos/scars) at the vaccination area(s) that would prevent appropriate dermatologic monitoring of the vaccination site(s) Fever greater than or equal to 38.0°C (100.4°F) at the time of planned vaccination Women who are pregnant or breastfeeding Acute illness at screening and unresolved at time of planned vaccination Employee of the investigational site

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: 37.5 µg LT patch<br>80 subjects will receive a two vaccination regimen with a LT patch. | Biological: heat-labile enterotoxin of E. coli (LT)<br>* Travelers' Diarrhea Vaccine System<br>* Other names: TD Vaccine System;|
| Placebo Comparator: Group 2: 0 µg LT patch (placebo)<br>40 subjects will receive a two vaccination regimen with a placebo patch. | Biological: Placebo<br>* Travelers' Diarrhea Vaccine System<br>* Other names: TD Vaccine System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) After First and Second Vaccination With LT Vaccine Patch and Comparison Against Placebo |  | Day 0, Day 14, Day 21, Day 28, Day 35, Day 90, Day 194 | 
| Geometric Mean Fold Ratio (GMFR) After First and Second Vaccination With LT Vaccine Patch and Comparison Against Placebo | GMFRs relative to the baseline titer were determined at each post-baseline time point. All GMFRs were based on log10-transformed data. | Day 14, Day 21, Day 28, Day 35, Day 90, Day 194 | 
| Seroconversion (SCR) After First and Second Vaccination With LT Vaccine Patch and Comparison Against Placebo | Definition of SCR: Seroconversion IgG: ≥ 2-fold rise of LT IgG titer relative to baseline Seroconversion IgA: ≥ 4-fold rise of LT IgA titer relative to baseline | Day 14, Day 21, Day 28, Day 35, Day 90, Day 194 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Safety of LT Vaccine Patch After First and Second Vaccination Compared to Placebo Patch | LT subjects (Group 1) were followed for six months longer (until Day 380) than Placebo subjects (Group 2) (until Day 194) | 13 months | 
| Evaluation of Residual LT in the Patch and on the Skin at the Patch Site Post-wear |  | 1 month | 
| Evaluation of LT-specific Immune Responses One-year After Original Treatment Regimen in LT Patch Group | GMT | 13 months | 
| Evaluation of LT-specific Immune Responses One Year After Original Treatment Regimen in LT Patch Group | GMFR | 13 months | 
| Evaluation of LT-specific Immune Responses One Year After Original Treatment Regimen in LT Patch Group | SCR | 13 months |