Tularemia
Conditions
Keywords
Live Vaccine Strain (LVS), Bacterial Infections, Ulceroglandular, Oculoglandular
Brief summary
This study is designed to determine the safety and immunogenicity of a Live Francisella tularensis Vaccine
Detailed description
Study was designed as a continuation of previously published research and targets subjects who were at risk of occupational exposure to F tularensis virus. Based on screening examinations; if a subject had a positive baseline titer (\<1:20) and gave no history of significant exposure to F tularensis or history of tularemia disease, had never received tularemia vaccination, and was at risk of exposure to F tularensis they could be enrolled in this protocol to receive vaccination. Subjects returned for follow-up exams on Days 1, 2, and 7; once between Days 12 and 16; and once between Days 28 and 35 post-vaccination. If titers; after blood samples on Days 28, 35 and 12 months showed \<1:20 the vaccination could be repeated at Days 56-84. If the repeat titer remained \<1:20, a booster vaccination could be administered. Subjects could be boosted 2 times with 1 year. If the titer measured 12 months after vaccination (+30 days) was \>1:20 and the subject had no lingering AEs, the subjects participation was considered complete.
Interventions
BIOLOGICALLive F tularensis Vaccine
Subjects will receive one drop of reconstituted F tularensis vaccine (approximately 0.0025 ml), applied with a bifurcated needle to the volar surface of the forearm, and the skin will be pricked 15 times over the prepared area. A booster dose will be given at the same dose volume and route of administration if the titer (days 56-84) is inadequate (\< 1:20).
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 65 Years
Healthy volunteers
Yes
Inclusion criteria
\> * At least 18 years old, or if on active military duty, 17 years old \> * Females of childbearing potential must agree to have a urine pregnancy test immediately before vaccination (Exception: documented hysterectomy or \> 3 years of menopause). The results must be negative. Volunteers must agree not to become pregnant for 3 months after receipt of the vaccine.\> * Subject must be actively enrolled in the SIP \> * Subjects must be considered at risk for exposure to F. tularensis.\> * Subjects must have an up-to-date (within 1 year) medical history, physical examination, and laboratory tests on 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 be willing to return for all follow-up visits on days 1, 2, 7, once between days 12-16, and once between days 28-35, days 56-84 (if needed), all visits for serology, as well as an annual visit while enrolled in protocol.\> * Volunteer must agree to report any Adverse Event which may or may not be associated with administration of the test article for at least 28 days after vaccination. All Serious and Unexpected Adverse Events will be reported for the duration of the volunteer's participation in the study. \>
Exclusion criteria
\> * Clinically significant abnormal lab results including evidence of Hepatitis C\*, Hepatitis B\* carrier state, or elevated liver function tests (2X normal values or at discretion of PI).\> * Personal history of an immunodeficiency or current treatment with an oral or intravenous immunosuppressive medication.\> * Confirmed HIV\* infection.\> * Any other medical condition at the discretion of the PI.\> * Antibiotic therapy for 7 days before vaccination.\> * Females must not be pregnant or lactating (females must agree to not become pregnant for 3 months after vaccination).\> * Any known allergies to excipients of the vaccine\> * Administration of another live vaccine within 4 weeks or an inactivated vaccine (generally) within 7 days of tularemia vaccination.\> * Any unresolved adverse event resulting from a previous immunization. \>
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Adverse Event Category Rates for All Vaccinations | AEs/SAEs recorded through duration of study; immunogenicity via MA on days 0, 28-35, 56-84, and at 1 year | AE analysis was conducted for all intent-to-treat subjects regardless of compliance with titer schedule. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity: Protocol Compliant Post-primary Titer Rates | 12 months | Percentage of subjects with less than or greater than titers (\> or \< 1:20) for compliant post-primary titers. |
| Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates | 12 months | Percentage of subjects with less than or greater than titers (\> or \< 1:20) who received post-boost 1 |
| Immunogenicity: Protocol-compliant Post-boost 2 Titer | 12 months | Percentage of subjects with less than or greater than titers who received post-boost 2. Responder = \> 1:20 Non-responder = \< 1:20 |
Countries
United States
Participant flow
Recruitment details
Enrollment at the Special Immunizations Clinic at USAMRIID is expected to last 5 years and include up to 1,000 subjects who were at risk of occupational exposure to F tularensis.
Participants by arm
| Arm | Count |
|---|---|
| F Tularensis Vaccine (0.0025 mL) Subjects receive a small amount of F tularensis vaccine (0.0025mL) placed on a cleansed site on the skin on the volar surface of the forearm. A bifurcated needle was used to make 15 superficial punctures at the vaccination site to permit percutaneous penetration of the vaccine.
Live F tularensis Vaccine: Subjects will receive one drop of reconstituted F tularensis vaccine (approximately 0.0025 ml), applied with a bifurcated needle to the volar surface of the forearm, and the skin will be pricked 15 times over the prepared area. A booster dose will be given at the same dose volume and route of administration if the titer (days 56-84) is inadequate (\< 1:20). | 405 |
| Total | 405 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screen Failure | 20 |
| Overall Study | Withdrawal by Subject | 59 |
Baseline characteristics
| Characteristic | F Tularensis Vaccine (0.0025 mL) |
|---|---|
| Age, Customized 20-29 years | 108 Participants |
| Age, Customized <20 years | 2 Participants |
| Age, Customized 30-39 years | 126 Participants |
| Age, Customized 40-49 years | 106 Participants |
| Age, Customized 50-59 years | 54 Participants |
| Age, Customized 60-69 years | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 382 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 13 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 357 Participants |
| Region of Enrollment United States | 405 participants |
| Sex: Female, Male Female | 145 Participants |
| Sex: Female, Male Male | 260 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 426 / 462 | 101 / 462 | 21 / 462 |
| serious Total, serious adverse events | 0 / 462 | 10 / 462 | 11 / 462 |
Outcome results
Primary
Safety: Adverse Event Category Rates for All Vaccinations
AE analysis was conducted for all intent-to-treat subjects regardless of compliance with titer schedule.
Time frame: AEs/SAEs recorded through duration of study; immunogenicity via MA on days 0, 28-35, 56-84, and at 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Any AE: Mild | 264 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Any AE: Moderate | 53 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Any AE: Severe | 11 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Local: Mild | 248 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Local: Moderate | 7 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Locale: Severe | 0 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Systemic: Mild | 121 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Systemic: Moderate | 48 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Systemic: Severe | 11 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Relationship: Unrelated | 30 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Relationship: Unlikely | 33 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Relationship: Possible | 86 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Relationship: Probable | 62 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Relationship: Definate | 246 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Outcome: Resolved | 271 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Outcome: Resolved with sequelae | 4 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Treatment required:None | 260 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Treatment required: Intervention required | 75 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Treatment required: Other | 7 Adverse events |
| Males | Safety: Adverse Event Category Rates for All Vaccinations | Treatment required: Hospitalization | 6 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Treatment required: Intervention required | 75 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Any AE: Mild | 162 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Relationship: Unlikely | 29 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Any AE: Moderate | 48 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Outcome: Resolved with sequelae | 1 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Any AE: Severe | 10 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Relationship: Possible | 77 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Local: Mild | 153 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Treatment required: Hospitalization | 6 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Local: Moderate | 13 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Relationship: Probable | 41 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Locale: Severe | 1 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Treatment required:None | 160 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Systemic: Mild | 105 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Relationship: Definate | 153 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Systemic: Moderate | 42 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Treatment required: Other | 1 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Systemic: Severe | 9 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Outcome: Resolved | 163 Adverse events |
| Females | Safety: Adverse Event Category Rates for All Vaccinations | Relationship: Unrelated | 28 Adverse events |
Secondary
Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates
Percentage of subjects with less than or greater than titers (\> or \< 1:20) who received post-boost 1
Time frame: 12 months
Population: As stated in the protocol, only titers taken in compliance with the prescribed schedule were used in the statistical analysis. 19 were compliant and analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Males | Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates | Days 28-35: <1:20 | 22.2 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates | Days 28-35: >1:20 | 77.8 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates | Days 56-84: <1:20 | 100.0 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates | Days 56-84: >1:20 | 0 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates | Month 12: <1:20 | 43.8 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates | Month 12: >1:20 | 56.3 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates | Overall: <1:20 | 26.3 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 1 Titer Rates | Overall: >1:20 | 73.7 Percentage of subjects |
Secondary
Immunogenicity: Protocol-compliant Post-boost 2 Titer
Percentage of subjects with less than or greater than titers who received post-boost 2. Responder = \> 1:20 Non-responder = \< 1:20
Time frame: 12 months
Population: As stated in the protocol, only titers taken in compliance with the prescribed schedule were used in the statistical analysis. 18 were compliant and analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Males | Immunogenicity: Protocol-compliant Post-boost 2 Titer | Overall: Responder | 94.7 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 2 Titer | Days 28-35: Non-Responder | 5.6 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 2 Titer | Days 28-35:Responder | 94.4 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 2 Titer | Days 56-84: Non-Responder | 25.0 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 2 Titer | Days 56-84: Responder | 75.0 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 2 Titer | Month 12: Non-Responder | 6.3 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 2 Titer | Month 12: Responder | 93.8 Percentage of subjects |
| Males | Immunogenicity: Protocol-compliant Post-boost 2 Titer | Overall: Non-Responder | 5.3 Percentage of subjects |
Secondary
Immunogenicity: Protocol Compliant Post-primary Titer Rates
Percentage of subjects with less than or greater than titers (\> or \< 1:20) for compliant post-primary titers.
Time frame: 12 months
Population: As stated in the protocol, only titers taken in compliance with the prescribed schedule were used in the statistical analysis. 454 were compliant and analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Males | Immunogenicity: Protocol Compliant Post-primary Titer Rates | Days 28-35: All subjects <1.20 | 4.1 Percentage of subjects |
| Males | Immunogenicity: Protocol Compliant Post-primary Titer Rates | Days 28-35: All subjects >1.20 | 95.9 Percentage of subjects |
| Males | Immunogenicity: Protocol Compliant Post-primary Titer Rates | Days 56-84: All subjects <1.20 | 73.3 Percentage of subjects |
| Males | Immunogenicity: Protocol Compliant Post-primary Titer Rates | Days 56-84: All subjects >1:20 | 26.7 Percentage of subjects |
| Males | Immunogenicity: Protocol Compliant Post-primary Titer Rates | Month 12: All subjects <1:20 | 3.6 Percentage of subjects |
| Males | Immunogenicity: Protocol Compliant Post-primary Titer Rates | Month 12: All subjects >1:20 | 96.4 Percentage of subjects |
| Males | Immunogenicity: Protocol Compliant Post-primary Titer Rates | Overall: <1:20 | 2.6 Percentage of subjects |
| Males | Immunogenicity: Protocol Compliant Post-primary Titer Rates | Overall: >1:20 | 97.4 Percentage of subjects |