Safety and Immunogenicity Study of Venezuelan Equine Encephalomyelitis (VEE) Vaccine as Booster Vaccine in Adults

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immunogenicity of VEE vaccine, C-84, TSI-GSD 205, Lot 7, Run 1, and collect data on the incidence of occupational VEE infection in vaccinated personnel.

Detailed Description
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Venezuelan Equine Encephalomyelitis Vaccine, Inactivated, Dried, C-84, TSI-GSD 205, Lot 7, Run 1, to be administered as dose(s) of 0.5 mL given subcutaneously in the upper outer aspect of the triceps area. Subjects who showed an initial immune response ≥ 1:20 to TC-83 and whose titer decreased over time or who rollover from a previous VEE C-84 protocol will receive a single 0.5 mL booster dose of C-84 vaccine. Subjects who were initial non-responders (< 1:20) to TC-83 will be given subcutaneous 0.5 mL injections on Days 0, 28-35, and 56-63. Duration of participation is 12-15 months if the subject demonstrates a PRNT80 of ≥1:20 at 1 year; if not, the vaccination procedure with C-84 will be repeated with a minimum of 28 days between doses. A maximum of four booster doses will be given in a year. If the PRNT80 titer is < 1:20 after four booster doses in any 12-month period, the subject's participation in the study will be placed on hold for 12 months; titers will be repeated at 1 year (± 30 days), and, if required, the subject will be given a booster dose of C-84 vaccine. Safety endpoint measurements will be evaluated for all subjects receiving at least one vaccination under this protocol regardless of compliance with the protocol. Immunogenicity endpoints will be evaluated for subjects who have been vaccinated in compliance with the protocol and who have had blood for titers drawn in compliance with the protocol.

Official Title
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Phase 2 Open-Label Safety and Immunogenicity Study of the Venezuelan Equine Encephalomyelitis (VEE) Vaccine, Inactivated, Dried, C-84, TSI-GSD 205, Lot 7, Run 1, as Booster Vaccination in Adult Subjects at Risk of Exposure to VEE Virus

Conditions
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Venezuelan Equine Encephalomyelitis

Intervention / Treatment
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* Biological: 0.5 mL Inactivated, Dried, C-84, TSI-GSD 205, Lot 7, Run 1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be 18 to 65 years old at time of consent Have received VEE TC-83 vaccine Have VEE plaque reduction neutralization 80% titers (PRNT80) <1:20 If female of childbearing potential, must agree to have a urine pregnancy test on the same day before each vaccination administration. (Exception: documented hysterectomy or >3 years of menopause). The results must be negative. Females just agree not to become pregnant for 3 months after receipt of the last study treatment (vaccination). Be considered at risk for exposure to VEE virus and who have submitted a Request for IND Vaccines for VDD vaccine. Sign and date the approved informed consent document and HIPAA Authorization. Have in their charts: medical history (including concomitant medications) within 60 days of planned first administration of vaccine physical examination and laboratory tests within 1 year previous chest radiograph results and electrocardiogram Be medically cleared for participation by an investigator (Examinations and/or tests may be repeated at the discretion of the PI). Be willing to return for all follow-up visits. Agree to report any adverse events (AEs) that may or may not be associated with administration of the vaccine for at least 28 days after administration and agree to report all serious adverse events (for example, resulting in hospitalization) for the duration of the subject's participation in the study. Agree to defer blood donation for 1 year after receipt of the vaccine. Exclusion Criteria: Have completed previous VEE C-84 vaccine study as a non-responder. Have clinically significant abnormal laboratory results (including evidence of hepatitis C, hepatitis B carrier state) or elevated liver function tests (two times the normal range or at the discretion of the PI). Have a personal history of an immunodeficiency or received treatment with an immunosuppressive medication, such as systemically administered glucocorticoids (eg, prednisone) within 1 month before planned administration of the vaccine or with other immunosuppressive therapies within 6 months of planned administration of the vaccine. Other immunosuppressive therapies include all cancer chemotherapeutic agents, drugs to prevent transplant rejection, interferons, monoclonal antibodies, protein kinase inhibitors, methotrexate, TNF (tumor necrosis factor) inhibitors, and any other drug determined to be immunosuppressive by the PI. Current administration of topical, inhalational, or intranasal glucocorticoids is not excluded. Have confirmed HIV infection. Have positive pregnancy test or be a breastfeeding female. Have any known allergies to components of the vaccine: Neomycin sulfate Streptomycin VEE virus, inactivated Formaldehyde Eggs Human serum albumin Guinea pig heart cells Sodium bisulfite Have had a previous serious allergic reaction to guinea pigs or guinea pig products. (Subjects who have known allergies to guinea pigs but whose allergic reactions were not severe may still participate in the study but should be referred to an allergy specialist for assessment and recommendation prior to vaccination). Have received or plan to receive another vaccine or investigational product within 28 days of VEE vaccination. Have any unresolved AE resulting from a previous immunization. Have a medical condition that, in the judgment of the PI, would impact subject safety.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects who successfully complete screening will be enrolled in the study to receive either (1) a series of booster(s) or (2) one booster vaccination(s). Each vaccination will be administered as 0.5 mL subcutaneous doses in the upper outer aspect of the arm (triceps areas)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Initial Non-responders to VEE TC-83 vaccinations<br>Venezuelan Equine Encephalomyelitis (VEE) Vaccine, Inactivated, Dried, C-84, TSI-GSD 205, Lot 7, Run 1, to be administered as dose(s) of 0.5 mL given subcutaneously in the upper outer aspect of the triceps area. | Biological: 0.5 mL Inactivated, Dried, C-84, TSI-GSD 205, Lot 7, Run 1<br>* administered as dose(s) of 0.5 mL given subcutaneously in the upper outer aspect of the triceps area. Subjects who showed an initial immune response ≥ 1:20 to TC-83 and whose titer decreased over time or who rollover from a previous VEE C-84 protocol will receive a single 0.5 mL booster dose of C-84 vaccine. Subjects who were initial non-responders (< 1:20) to TC-83 will be given subcutaneous 0.5 mL injections on Days 0, 28-35, and 56-63<br>|
| Experimental: Cohort B: Responders to TC-83 or previous C-84 vaccinations<br>Subjects who showed an initial immune response ≥ 1:20 to TC-83 and whose titer decreased over time or who rollover from a previous VEE C-84 protocol will receive a single 0.5 mL booster dose of C-84 vaccine. Subjects who were initial non-responders (< 1:20) to TC-83 will be given subcutaneous 0.5 mL injections on Days 0, 28-35, and 56-63 | Biological: 0.5 mL Inactivated, Dried, C-84, TSI-GSD 205, Lot 7, Run 1<br>* administered as dose(s) of 0.5 mL given subcutaneously in the upper outer aspect of the triceps area. Subjects who showed an initial immune response ≥ 1:20 to TC-83 and whose titer decreased over time or who rollover from a previous VEE C-84 protocol will receive a single 0.5 mL booster dose of C-84 vaccine. Subjects who were initial non-responders (< 1:20) to TC-83 will be given subcutaneous 0.5 mL injections on Days 0, 28-35, and 56-63<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Develop titers of >1:20 | The primary immunogenicity endpoint measurements will be the percentage of per-protocol subjects who develop titers of ≥ 1:20 as determined by PRNT80 after VEE vaccination at each scheduled time point for which blood samples are drawn and over the entire study period to study completion. | Month 12-15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMT for PRNT80 Titers of Subjects at Each Scheduled Time Point | The geometric mean PRNT80 titers of per-protocol subjects at each scheduled time point for which blood samples are drawn and over the entire study period to study completion. | Month 12-15 | 
| Percentage of Subjects with Adverse Events (AEs) Following Vaccination | Safety will be evaluated by the nature (body system affected), type [local or systemic], severity, relationship to vaccine, treatment or intervention offered if any, and resolution or outcome) and frequency of AEs for the assessment population | Month 12-15 | 
| Percentage of Subjects with Each AE Type (local or systemic) | Safety will be evaluated by the nature (body system affected), type [local or systemic], severity, relationship to vaccine, treatment or intervention offered if any, and resolution or outcome) and frequency of AEs for the assessment population | Month 12-15 |