Rift Valley Fever
Conditions
Keywords
Hemorrhagic Fever, Viral Infections, Neurologic diseases, Arbovirus Infections, RVF
Brief summary
This study is designed to determine the safety and immunogenicity of a Rift Valley Fever (RVF) Vaccine
Detailed description
Study Objectives: The objectives of this two-part, primary immunization and booster dose, study are to continue to collect safety data on Rift Valley Fever (RVF) Vaccine, Inactivated (TSI-GSD 200); and, to continue to collect immunogenicity data on Rift Valley Fever (RVF) Vaccine, Inactivated (TSI-GSD 200) and analyze interim data to determine whether a 6-month dose is indicated; and, to provide potential protection for personnel at risk for occupational exposure to the RVF virus and collect data on incidence of occupational RVF infection (subclinical and clinical) in immunized personnel.
Interventions
BIOLOGICALTSI-GSD 200 RVF Vaccine
Part A: Inactivated, Dried (TSI-GSD 200) RVF vaccine will be given as three 1.0-ml subcutaneous primary series injections, with doses on day 0, once on days 7-14, once on days 28-42 (the third dose will be given at least 21 days after the second dose).Part B: Subcutaneous 1.0-ml booster doses (maximum of four boosters over 12 months) will be given if the volunteer fails to respond to the primary series with a PRNT80 ≥ 1:40 or annually if titer wanes to \< 1:40.
Sponsors
U.S. Army Medical Research and Development Command
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Parts A & B: * At least 18 years old, or if active military duty, 17 years old, * Females of childbearing potential must agree to have a urine pregnancy test within 48 hours before receipt of each dose of vaccine. The test results must be negative. Females will be advised not to become pregnant for 3 months after the primary series and each booster dose, and must not be breast-feeding, * Subject must be actively enrolled in the SIP to be vaccinated at USAMRIID or be otherwise authorized (with documentation) by the DOD * Subjects must be at risk for exposure to RVF virus, * Subjects 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 may be repeated within 1 year at the discretion of the enrolling physician. * Volunteer must have signed and dated the approved informed consent (Volunteer Agreement Explanation and Affidavit). Additional Inclusion Criteria for Part B: • Completion of primary series and any follow-up titer (PRNT80) \< 1:40 from the current or a previous RVF IND 365 protocol.
Exclusion criteria
Parts A & B: * Clinically significant abnormal lab results including evidence of Hepatitis C, Hepatitis B or carrier state, or elevated liver function tests. * Personal history of immunodeficiency or current treatment with immunosuppressive medication, at the discretion of the physician. * Confirmed HIV infection. * Any medical condition that, at the discretion of the physician, may jeopardize the safety of the volunteer. * Any serious or life-threatening allergies to any component of the vaccine: formalin, human serum albumin, neomycin, streptomycin * Administration of any other vaccine within 28 days of any dose of RVF vaccine. * Any unresolved adverse event resulting from a previous immunization. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: All Incidences of Erythema | 12 months | Collect data on the occurrence of AEs and SAEs in reference to Erythema (most frequently reported AE) in parts A and B of the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity: Geometric Mean Titers After 3rd Vaccination | 28 days after dose 3 | Measurement is the 80% plaque-reduction neutralization titer (PRNT80) antibodies to RVF virus following 3rd vaccination (Parts A and B of study) |
| Immunogenicity: Geometric Mean Titers Before 6-month Booster | Before 6-month booster | Measurement is the 80% plaque-reduction neutralization titer (PRNT80) for study Parts A and B |
| Immunogenicity: Geometric Mean Titers at 12 Months | at 12 months | Measurement is the 80% plaque-reduction neutralization titer (PRNT80) for study Parts A and B. |
| Immunogenicity: Geometric Mean Titers After 6-month Booster | month 6 after dose 4 | Measurement is the 80% plaque-reduction neutralization titer (PRNT80) for study Parts A and B. |
Countries
United States
Participant flow
Recruitment details
278 subjects were enrolled at USAMRIID to participate
Participants by arm
| Arm | Count |
|---|---|
| TSI-GSD 200 RVF Vaccine Part A: Inactivated, Dried (TSI-GSD 200) RVF vaccine, will be given as three 1.0-ml subcutaneous primary series injections, with doses on day 0, once on days 7-14, once on days 28-42 (the third dose will be given at least 21 days after the second dose).Part B: Subcutaneous 1.0-ml booster doses (maximum of four boosters over 12 months) will be given if the volunteer fails to respond to the primary series with a PRNT80 ≥ 1:40 or annually if titer wanes to \< 1:40.
TSI-GSD 200 RVF Vaccine: Part A: Inactivated, Dried (TSI-GSD 200) RVF vaccine will be given as three 1.0-ml subcutaneous primary series injections, with doses on day 0, once on days 7-14, once on days 28-42 (the third dose will be given at least 21 days after the second dose).Part B: Subcutaneous 1.0-ml booster doses (maximum of four boosters over 12 months) will be given if the volunteer fails to respond to the primary series with a PRNT80 ≥ 1:40 or annually if titer wanes to \< 1:40. | 153 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other | 135 |
Baseline characteristics
| Characteristic | TSI-GSD 200 RVF Vaccine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 153 Participants |
| Region of Enrollment United States | 153 participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 153 |
| other Total, other adverse events | 75 / 153 |
| serious Total, serious adverse events | 11 / 153 |
Outcome results
Primary
Safety: All Incidences of Erythema
Collect data on the occurrence of AEs and SAEs in reference to Erythema (most frequently reported AE) in parts A and B of the study
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TSI-GSD 200 RVF Vaccine | Safety: All Incidences of Erythema | Mild | 15 number of events |
| TSI-GSD 200 RVF Vaccine | Safety: All Incidences of Erythema | Moderate | 10 number of events |
| TSI-GSD 200 RVF Vaccine | Safety: All Incidences of Erythema | Severe | 0 number of events |
Secondary
Immunogenicity: Geometric Mean Titers After 3rd Vaccination
Measurement is the 80% plaque-reduction neutralization titer (PRNT80) antibodies to RVF virus following 3rd vaccination (Parts A and B of study)
Time frame: 28 days after dose 3
Population: Population is based on responders (defined as a subject achieving a PRNT80 \>1:40)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| TSI-GSD 200 RVF Vaccine | Immunogenicity: Geometric Mean Titers After 3rd Vaccination | Male: GMT | 47.3 Titers |
| TSI-GSD 200 RVF Vaccine | Immunogenicity: Geometric Mean Titers After 3rd Vaccination | Female: GMT | 74.9 Titers |
Secondary
Immunogenicity: Geometric Mean Titers After 6-month Booster
Measurement is the 80% plaque-reduction neutralization titer (PRNT80) for study Parts A and B.
Time frame: month 6 after dose 4
Population: Population is based on responders (defined as a subject achieving a PRNT80 \>1:40)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| TSI-GSD 200 RVF Vaccine | Immunogenicity: Geometric Mean Titers After 6-month Booster | Male: GMT | 211.8 Titers |
| TSI-GSD 200 RVF Vaccine | Immunogenicity: Geometric Mean Titers After 6-month Booster | Female: GMT | 189.0 Titers |
Secondary
Immunogenicity: Geometric Mean Titers at 12 Months
Measurement is the 80% plaque-reduction neutralization titer (PRNT80) for study Parts A and B.
Time frame: at 12 months
Population: Population is based on responders (defined as a subject achieving a PRNT80 \>1:40)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| TSI-GSD 200 RVF Vaccine | Immunogenicity: Geometric Mean Titers at 12 Months | Male: GMT | 48.8 Titers |
| TSI-GSD 200 RVF Vaccine | Immunogenicity: Geometric Mean Titers at 12 Months | Female: GMT | 48.4 Titers |
Secondary
Immunogenicity: Geometric Mean Titers Before 6-month Booster
Measurement is the 80% plaque-reduction neutralization titer (PRNT80) for study Parts A and B
Time frame: Before 6-month booster
Population: Population is based on responders (defined as a subject achieving a PRNT80 \>1:40)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| TSI-GSD 200 RVF Vaccine | Immunogenicity: Geometric Mean Titers Before 6-month Booster | Male: GMT | 8.5 Titers |
| TSI-GSD 200 RVF Vaccine | Immunogenicity: Geometric Mean Titers Before 6-month Booster | Female: GMT | 23.9 Titers |