Safety and Immunogenicity of Venezuelan Equine Encephalomyelitis Vaccine (VEE C-84) as a Booster to VEE TC-83

Study Overview
=================
Brief Summary
-----------------
The study is designed to assess the safety and immunogenicity of Venezuelan Equine Encephalomyelitis Vaccine, Inactivated, Dried, C-84, TSI GSD 205, as a booster vaccination.

Detailed Description
-----------------
Study Objectives: Primary: To assess safety of Venezuelan Equine Encephalomyelitis Vaccine, Inactivated, Dried, C-84, TSI GSD 205, as a booster vaccination as a single dose or a three-dose series, and To assess immunogenicity of Venezuelan Equine Encephalomyelitis Vaccine, Inactivated, Dried, C-84, TSI GSD 205, as a booster vaccination as a single dose or a three-dose series Secondary: To assess incidence of VEE infection in C-84 boosted personnel.

Official Title
-----------------
A Phase 2 Open-Label, Safety and Immunogenicity Study of Venezuelan Equine Encephalomyelitis Vaccine, Inactivated, Dried, C-84, TSI-GSD 205 When Used as a Booster After TC-83 Primary Immunization in Healthy Adults At-Risk for Exposure to Virulent Venezuelan Equine Encephalomyelitis Virus

Conditions
-----------------
Venezuelan Equine Encephalomyelitis

Intervention / Treatment
-----------------
* Biological: VEE C-84


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: At least 18 years old. VEE PRNT80 < 1:20 before immunization. (females) Negative urine pregnancy test on the same day before vaccination. Not planning pregnancy for 3 months. Actively enrolled in the SIP. At risk for exposure to virulent VEE virus (with up-to-date risk assessment). Previous TC-83 vaccination Up-to-date (within 1 year) physical examination/tests. Sign and date the approved informed consent. Willing to return for all follow-up visits. Agree to report adverse event (AE) up to 28 days after vaccination. Exclusion Criteria: Over age of 65 years Clinically significant abnormal lab results including evidence of Hepatitis C, Hepatitis B carrier state, or elevated liver function tests. History of immunodeficiency or current treatment with immunosuppressive medication. (females) Currently breastfeeding. Confirmed human immunodeficiency virus (HIV) titer. Any known allergies to components of the vaccine. A medical condition that in the judgment of the Principal Investigator (PI) would impact subject safety (i.e-vaccination and or exposure to another alphavirus). Administration of any vaccine within 28 days of C-84. Any unresolved AEs resulting from a previous immunization.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccine<br>VEE C-84 - Venezuelan Equine Encephalomyelitis Vaccine, Inactivated, Dried, C-84, TSI-GSD 205 | Biological: VEE C-84<br>* Subjects will receive a 0.5 mL subcutaneous injection in the upper outer aspect of arm; maximum of four boosters in 1 year if titer <1:20.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events (ITT) | Frequency of the following adverse events will be evaluated for all intent-to-treat subjects: headache, myalgia, fever, fatigue, sore throat, erythema, tenderness, and warmth. | Day 28 after each booster dose | 
| Immunogenicity: TC-83 with PRNT80 ≥ 1:20 | Number of initial responders to TC-83 with PRNT80 ≥ 1:20 after C-84 booster dose. | Between Days 28 and 35 after each booster dose | 
| Immunogenicity: TC-83 with PRNT80 ≥ 1:20 | Number of initial responders to TC-83 with PRNT80 ≥ 1:20 after C-84 booster dose. | 12-15 months after booster dose | 
| Immunogenicity: TC-83 with PRNT80 < 1:20 | Number of initial responders to TC-83 who are non-responders (PRNT80 < 1:20) to C-84 booster dose. | Between Days 28 and 35 after each booster dose | 
| Immunogenicity: TC-83 with PRNT80 < 1:20 | Number of initial responders to TC-83 who are non-responders (PRNT80 < 1:20) to C-84 booster dose. | 12-15 months after vaccination | 
| Immunogenicity: TC-83 with PRNT80 ≥ 1:20 after three booster doses |  | After three booster doses | 
| Immunogenicity: TC-83 with PRNT80 ≥ 1:20 12- 15 months after first booster dose |  | 12- 15 months after first booster dose | 
| Immunogenicity: PRNT80 ≥ 1:20 after 1 dose | Number of rollovers from past C-84 booster study with PRNT80 ≥ 1:20 after 1 dose. | After 1 dose | 
| Immunogenicity: PRNT80 ≥ 1:20 12-15 months post dose for new C-84 Protocol. |  | 12-15 months post dose for new C-84 Protocol | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VEE disease among vaccinated subjects who achieved a PRNT80 ≥ 1:20. | The number of confirmed cases of VEE disease among vaccinated subjects who achieved a PRNT80 ≥ 1:20. | Length of the study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Encephalitis, Viral Infections, Neurologic diseases, Alphavirus Infections, VEE