LT Vaccine Patch Self-Administration Study

Study Overview
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Brief Summary
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To evaluate the immune responses achieved following self-administered heat-labile enterotoxin of E. coli (LT) vaccination by transcutaneous immunization compared to the immune responses achieved by clinician-administered vaccination.

Official Title
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A Phase 2, Randomized, Open-Label Study to Compare the Immunogenicity and Safety of a Self-Administered LT Vaccine Patch With an LT Vaccine Patch Administered by a Clinician

Conditions
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Prevention of Travelers' Diarrhea

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible to participate in the study: Healthy adult males or females 18-64 years of age with signed Informed Consent. Women who are not post-menopausal or surgically sterile must have a negative serum or urine pregnancy test at screening and within 24 hours of each vaccination with understanding (through Informed Consent process) to not become pregnant over the duration of the study, and must agree 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: Subjects meeting any of the following criteria are not eligible for participation in the study: 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 Donated blood or blood products such as plasma within the past 30 days 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 traveler's diarrhea in the previous two years 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 (GI) 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 at the vaccination area(s) that would interfere with patch adhesion in the opinion of the Investigator 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 or at baseline; or 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>40 subjects will have skin prepared using SPS:Buffer and will receive 37.5ug LT patch on the left deltoid by a Clinician on Day 0. Two weeks later will have the same treatment repeated on the right deltoid by the clinician | Biological: heat-labile enterotoxin of E. coli (LT)<br>* 37.5ug patch applied on either the deltoid or the thigh<br>* Other names: TD Vaccine System;|
| Experimental: Group 2<br>40 subjects will be pretreated with SPS:Buffer and a patch containing 37.5ug will be applied on the left deltoid by the Clinician. Fourteen days later, the same procedure will occur on the left thigh by the clinician. | Biological: heat-labile enterotoxin of E. coli (LT)<br>* 37.5ug patch applied on either the deltoid or the thigh<br>* Other names: TD Vaccine System;|
| Experimental: Group 3<br>40 subjects will have skin prepared using SPS:Buffer and will receive 37.5ug LT on the left deltoid by the clinician. Two weeks later subject will have the same treatment repeated by self-application in the clinic on the left thigh. | Biological: heat-labile enterotoxin of E. coli (LT)<br>* 37.5ug patch applied on either the deltoid or the thigh<br>* Other names: TD Vaccine System;|
| Experimental: Group 4<br>40 subjects will have skin prepared using SPS:Buffer and will have 37.5ug LT patch on the left deltoid by a clinician. Two weeks later subjects will have the same treatment repeated by self-application at home on the left thigh. | Biological: heat-labile enterotoxin of E. coli (LT)<br>* 37.5ug patch applied on either the deltoid or the thigh<br>* Other names: TD Vaccine System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMTs After a Self-administered LT Vaccine Patch (In-clinic or Away From Clinic) Compared to a Clinician-administered LT Vaccine Patch. | The primary endpoint of this trial was to compare the immunogenicity (i.e., GMTs, GMFRs and seroconversion rates for LT IgG and IgA) of subject self-administered [second] vaccination with clinician-administered [second] vaccination, using the deltoid/thigh (Vaccination 1/Vaccination 2) treatment regimen. GMT: geometric mean titer | Day 0, Day 14, Day 21, Day 28, Day 35, Day 194 | 
| GMFR After a Self-administered LT Vaccine Patch (In-clinic or Away From Clinic) Compared to a Clinician-administered LT Vaccine Patch. | The primary endpoint of this trial was to compare the immunogenicity (i.e., GMTs, GMFRs and seroconversion rates for LT IgG and IgA) of subject self-administered [second] vaccination with clinician-administered [second] vaccination, using the deltoid/thigh (Vaccination 1/Vaccination 2) treatment regimen. GMFR: geometric mean fold ratio GMFRs relative to the baseline titer were determined for LT IgG and LT IgA at each post-baseline time point. All GMFRs were based on log10-transformed data. | Day 14, Day 21, Day 28, Day 35, Day 194 | 
| Seroconversion After a Self-administered LT Vaccine Patch (In-clinic or Away From Clinic) Compared to a Clinician-administered LT Vaccine Patch. | The primary endpoint of this trial was to compare the immunogenicity (i.e., GMTs, GMFRs and seroconversion rates (SCR) for LT IgG and IgA) of subject self-administered [second] vaccination with clinician-administered [second] vaccination, using the deltoid/thigh (Vaccination 1/Vaccination 2) treatment regimen. seroconversion (SC): two-fold or greater rise in titer relative to Day 0 for LT IgG and a four-fold or greater rise in titer relative to Day 0 for LT IgA | Day 14, Day 21, Day 28, Day 35, Day 194 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events for Self-administered LT Vaccine Patch and Comparison to the Clinician-administered LT Vaccine Patch |  | 6 months | 
| Evaluation of Immunogenicity (GMT) for Deltoid/Thigh (Prime/Boost) Versus Deltoid/Deltoid Administered LT Vaccine. |  | 6 months | 
| Safety for Self-administration In-clinic Compared to Self-administration Away From the Clinic. |  | 6 months | 
| Evaluation of Immunogenicity (GMT) for Self-administration In-clinic Compared to Self-administration Away From the Clinic. |  | 6 months | 
| Evaluation of Immunogenicity (GMFR) for Deltoid/Thigh (Prime/Boost) Versus Deltoid/Deltoid Administered LT Vaccine |  | 6 months | 
| Evaluation of Immunogenicity (SCR) for Deltoid/Thigh (Prime/Boost) Versus Deltoid/Deltoid Administered LT Vaccine |  | 6 months | 
| Evaluation of Immunogenicity (GMFR) for Self-administration In-clinic Compared to Self-administration Away From the Clinic |  | 6 months | 
| Evaluation of Immunogenicity (SCR) for Self-administration In-clinic Compared to Self-administration Away From the Clinic |  | 6 months |