Safety and Immunogenicity Study of Eastern Equine Encephalitis (EEE) Vaccine

Study Overview
=================
Brief Summary
-----------------
This study is designed to determine the safety and immunogenicity of Eastern Equine Encephalitis (EEE) Vaccine.

Detailed Description
-----------------
This was an open-label, vaccine study of Eastern Equine Encephalitis Vaccine, Inactivated Dried, EEE, TSI-GSD 104 in healthy, adult subjects. No concurrent control group was used. The controls used in this study to assess immunogenicity were historical PRNT80 values obtained in past studies of the EEE vaccine. Rates of adverse events (AEs) were tabulated by relationship to product administration and severity. The primary objectives are to assess the safety of Eastern Equine Encephalitis Vaccine, Inactivated, Dried EEE, TSI GSD 104, and to assess immunogenicity of Eastern Equine Encephalitis Vaccine, Inactivated, Dried EEE, TSI GSD 104.

Official Title
-----------------
A Multi-Site Phase 2 Open-Label, Safety and Immunogenicity Study of Eastern Equine Encephalitis Vaccine, Inactivated, Dried, TSI-GSD 104 in Healthy Adults At Risk for Exposure to Eastern Equine Encephalitis Virus

Conditions
-----------------
Eastern Equine Encephalitis

Intervention / Treatment
-----------------
* Biological: Inactivated, Dried, TSI-GSD 104, EEE


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: At least 18 years old. EEE PRNT80 ≤ 1:20. EEE PRNT80 ≤ 1:40 for booster series (females) Negative pregnancy test on the same day before vaccination. Not planning pregnancy for 3 months. At risk for exposure to virulent EEE virus (with up-to-date risk assessment). 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 events (AE) up to 28 days after each vaccination. Exclusion Criteria: Over 65 years of age (for Primary Immunization). Clinically significant abnormal lab results including evidence of Hepatitis C, Hepatitis B carrier state, or elevated (2X normal) 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 or exposure to another Alphavirus). Administration of any IND product or live vaccine within 28 days of EEE. 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: Vaccination<br>Inactivated, Dried, TSI-GSD 104, EEE | Biological: Inactivated, Dried, TSI-GSD 104, EEE<br>* Subjects will receive 0.5ml SQ, as a two-dose primary series (days 0 and 28) and 0.1ml, as a mandatory booster dose at 6 months. A booster dose may be administered before 6 months if PRNT80 is < 1:40 after day 28. Up to four booster doses may be given in any 1-year period.<br>* Other names: EEE A-14568;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Response Rates for PRNT80 Titers | Subject response rates for PRNT80 titers for vaccinations and all boosters. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. Four to 5 weeks for primary vaccinations (3) and up to four boost doses in 1 year period for a total duration of up to 5 years (anticipated duration of study execution). | 5 years | 
| Response Rates of Post Dose 2: Day 21-35 PRNT80 Titers | Subject response rates for PRNT80 titers for post dose 2, days 21-35. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. | Post dose 2, days 21-35 | 
| Response Rates of Pre-Month 6 PRNT80 Titers | Subject response rates for PRNT80 titers of pre-month 6. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. | Pre-month 6 | 
| Response Rates of Post Month 6: Day 21-35 PRNT80 Titers | Subject response rates for PRNT80 titers for post month 6, days 21-35. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. | Post month 6, days 21-35 | 
| Response Rates of Post Booster 1: Day 21-35 PRNT80 Titers | Subject response rates for PRNT80 titers for post booster 1, days 21-35. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. | Post booster 1, days 21-35 | 
| Response Rates of Annual (11-13 Months) PRNT80 Titers | Subject annual response rates for PRNT80 titers for months 11-13. The per-protocol population was used for immunogenicity analyses. Only subjects who were vaccinated according to the schedule defined in the protocol were included in the per-protocol population. Only observations or specimens collected according to the protocol were included in the analyses using the per protocol population. If a subject received one or more treatments out of compliance with the protocol schedule, any observations or specimens collected after the out-of-compliance treatment were excluded from the analyses using the per-protocol population. | Months 11-13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subject Experiencing Local and Systemic Adverse Events | Number of subjects of who experienced and didn't experience local and systemic adverse events after vaccination and booster. | vaccination/booster days 0-28 for up to 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
EEE