Phase 2 Safety and Immunogenicity Study of Rift Valley Fever Vaccine

Study Overview
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Brief Summary
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This study is to collect safety and immunogenicity data for an Rift Valley Fever (RVF) vaccine

Detailed Description
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This study is being conducted to collect safety and immunogenicity data for the RVF vaccine, TSI-GSD 200, Lot 7, Run 2. Enrollment in this protocol is offered for personnel who enter areas where this virus is used in research or is endemic (an area where this disease process is found to occur frequently). Subjects who respond with a titer of >1:40 may participate for study duration. Rift Valley Fever Vaccine, Inactivated, Dried (TSI GSD 200) will be administered in 1.0-mL doses SQ in the upper outer aspect of the arm.

Official Title
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A Phase 2 Open Label Safety and Immunogenicity Study of Rift Valley Fever Vaccine, Inactivated, Dried, TSI-GSD 200, Lot 7, Run 2, in Adult Subjects at Risk of Exposure to Rift Valley Fever Virus

Conditions
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Rift Valley Fever

Intervention / Treatment
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* Biological: RVF Vaccine


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 RVF plaque reduction neutralization 80% titers (PRNT80) <1:10 for primary series. Have RVF PRNT80 (plaque reduction neutralization 80% titer) <1:40 for booster series. If female of childbearing potential, must agree to have a urine pregnancy test on the same day before each vaccine administration. (Exception: documented hysterectomy or ≥3 years of menopause.) The results must be negative. Females must agree not to become pregnant for 3 months after receipt of the last study treatment (vaccination). Be considered at risk for exposure to RVF virus and who have submitted a Request for IND Vaccines for the RVF 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 RVF vaccine study as a nonresponder (PRNT80 <1:40). 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 breastfeeding female. Have any known allergies to components of the vaccine: Fetal rhesus monkey lung cells Formaldehyde Neomycin sulfate Streptomycin Sodium bisulfite Human serum albumin (HAS) RVF virus (Entebbe strain) Have administration of another vaccine or investigational product within 28 days of RVF 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
Intervention Model: Single Group Assignment
Interventional Model Description: vaccine to be administered in 1.0mL doses SQ in the upper outer aspect of the arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RVF Vaccine<br>1.0 mL dose given SQ in upper arm | Biological: RVF Vaccine<br>* 1.0 mL dose given SQ in upper arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects with Local and Systemic Adverse Events and Their Relationship to the Study Vaccine | Safety assess of local and systemic adverse events and their relationship to the study vaccine. AEs will be recorded for 28 days after each dose of the vaccine for the assessment population (all subjects who receive at least one vaccination under this protocol. Subjects will be contacted by study staff via e-mail or telephone the day after vaccination (Day 1) and once per week for 4 weeks after each vaccination to discuss any reactions. | 0-28 days after each dose | 
| Percentage of Subjects Who Developed Titers of ≥1:40 of Per-protocol Subjects | Percentage of per-protocol subjects (subjects who adhered to the protocol schedule for both vaccination and blood collects) who developed titers ≥1:40 as determined by PRNT80 (plaque reduction neutralization 80% titer) after vaccination at each scheduled time point for which blood samples are drawn and over the entire study period. | 21-35 days after each vaccination and month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Severity of Adverse Events | Frequency and severity of adverse events for the assessment population (all subjects who receive at least one vaccination under this protocol). Subjects will be contacted by study staff via e-mail or telephone the day after vaccination (Day 1) and once per week for 4 weeks after each vaccination to discuss any reactions. | 0-28 days after each dose | 
| Geometric Mean PRNT80 (plaque reduction neutralization 80% titer) of Per-protocol Subjects | Geometric mean PRNT80 (plaque reduction neutralization 80% titer) of per-protocol subjects at each scheduled time point for which blood samples are drawn and over the entire study period to study completion. | 21-35 days after each vaccination and month 12 |