Safety and Immunogenicity Study of Rift Valley Fever Vaccine, Inactivated

Study Overview
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Brief Summary
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This study is designed to determine the safety and immunogenicity of an inactivated Rift Valley Fever (RVF) Vaccine in adults

Detailed Description
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The primary objectives are to assess safety of Rift Valley Fever (RVF) Vaccine, Inactivated (TSI-GSD 200) and to assess immunogenicity of Rift Valley Fever (RVF) Vaccine, Inactivated (TSI-GSD 200). The secondary objective is to assess incidence of RVF infection in vaccinated personnel

Official Title
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Long-Term Open-Label Primary Vaccination and Booster Dose Study of the Safety and Immunogenicity of Rift Valley Fever Vaccine, Inactivated, Dried (TSI-GSD 200) in At-Risk Adults

Conditions
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Rift Valley Fever

Intervention / Treatment
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* Biological: Inactivated, Dried (TSI-GSD 200), RVF Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years old. Females of childbearing potential must have a negative serum or urine pregnancy test within 48 hours before each vaccination. Females will be advised not to become pregnant for 3 months after the primary series and each booster dose. Females must not be breast-feeding. Subject must be at risk for exposure to RVF virus. Subject must have an up-to-date (within 1 year) medical history, physical examination, and laboratory tests in their charts and be medically cleared for participation by an investigator. Examinations or tests to qualify for enrollment may be repeated at the discretion of the investigators. Subject must sign and date the approved informed consent document. For initiation of primary series, RVF PRNT80 <1:10. For RE-ENTRY into this protocol or ROLLOVER from an earlier RVF protocol to receive a booster, RVF PRNT80 <1:40 within past 1 year Exclusion Criteria: Older than 65 years of age for the primary series vaccination (able to receive booster doses if no other contraindications). Clinically significant abnormal lab results, including evidence of Hepatitis C, Hepatitis B carrier state, or elevated (2 times normal) liver function tests. Personal history of immunodeficiency or current treatment with immunosuppressive medication. Confirmed positive human immunodeficiency virus (HIV) titer. Any medical condition that, at the discretion of the physician, may jeopardize the safety of the subject. Any serious or life-threatening allergies to any component of the vaccine: formalin human serum albumin neomycin streptomycin fetal rhesus lung cells RVF virus inactivated Administration of any Investigational New Drug (IND) product or any vaccine within the 28 days before RVF vaccination. Any unresolved adverse event resulting from a previous immunization.

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: Open-label, Phase 2, uncontrolled, vaccine study to assess the safety, immunogenicity of RVF (inactivated) vaccine (1.0 mL subcutaneous, SQ). Three primary series doses; for responders to the vaccine (PRNT80 ≥ 1:40), 6 month mandatory vaccine booster dose; Three primary series doses; for non-responders to the vaccine (PRNT80 < 1:40) may be boosted before 6 months.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: primary vaccination with boost<br>Inactivated, Dried (TSI-GSD 200), RVF Vaccine | Biological: Inactivated, Dried (TSI-GSD 200), RVF Vaccine<br>* All subjects: 1.0-mL (SQ)doses on day 0, once between days 7 & 14, & once between days 28-42. Initial responders: A 6-month mandatory vaccine booster dose (1.0 mL, SQ) will be given if the PRNT80 is ≥1:40 after the primary series. Subsequent booster doses will be given for PRNT80 titer <1:40. Initial non-responders: Individual who has a PRNT80 titer <1:40 following the primary series may be administered a booster dose before 6 months. The individual will not receive the mandatory 6-month booster dose. Once an initial non-responder achieves PRNT80 ≥1:40, additional booster doses will be given for subsequent PRNT80 <1:40). All subjects: RVF booster dose will be administered within 90 days after a PRNT80 result of <1:40.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PRNT80 ≥ 1:40 after primary series | % vaccinated subjects with PRNT80 ≥ 1:40 after primary series (initial responders). | Between Days 28-42 | 
| PRNT80 ≥ 1:40 after 6-month mandatory booster dose | % vaccinated subjects with PRNT80 ≥ 1:40 after 6-month mandatory booster dose (initial responders only). | 7 months | 
| (PRNT80 < 1:40) who responded with a PRNT80 ≥ 1:40 | % initial non-responders (PRNT80 < 1:40) who responded with a PRNT80 ≥ 1:40 after 1, 2, 3, or 4 booster doses. | up to 5 years | 
| Median duration of PRNT80 ≥ 1:40 in initial responders | Median duration of PRNT80 ≥ 1:40 in initial responders after the primary series and 6-month mandatory booster dose. | up to 5 years | 
| Median duration of PRNT80 ≥ 1:40 in initial non-responders | Median duration of PRNT80 ≥ 1:40 in initial non-responders after the first booster dose that results in PRNT80 ≥ 1:40. | up to 5 years | 
| Number of booster doses needed in initial non-responders to achieve PRNT80 ≥ 1:40 | Number of booster doses needed in initial non-responders to achieve PRNT80 ≥ 1:40. | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects without symptoms | Number of subjects without symptoms | 5 years | 
| Subjects with any category of local reaction (grade 1-4). | Number of subjects with any local reaction | 5 years | 
| Subjects with mild, moderate, severe, and potentially life-threatening systemic reactions (grade 1-4). | Number of subjects with systemic reactions | 5 years | 
| Subjects with generalized allergic reactions | Number of subjects with generalized allergic reactions | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemorrhagic Fever, Viral Infections, Neurologic diseases, Arbovirus Infections, RVF