FY15-14: Tularemia Vaccine Protocol (NDBR Lot 4)

This protocol is replacing NCT00787826 (S-09-15; FY07-15)

The study population will consist of USAMRIID and qualified extramural participants who are
at risk of exposure to tularemia bacteria. This study will be performed at the USAMRIID SIP
Clinic. This open-label study represents a continuation of previous research conducted at
USAMRIID.

After the enrollment and approval for participation, each subject will be vaccinated with a
bifurcated needle; approximately 0.06 mL of the reconstituted vaccine will be placed on the
volar surface of the forearm and applied by multiple puncture. The subject will return for
follow-up examination on Days 1 and 2; between Days 5-9, 12-16, and 28-35; and at 6 months (±
14 days) after vaccination for clinical evaluation of AEs and to document responses to the
vaccine. Additionally, the subject may be asked to return between Days 56-84 for a repeat
titer if indicated and ordered by an investigator on the study. The subject's participation
in this study will be considered complete at 6 months ± 14 days after vaccination or
revaccination. Following documentation of a positive "take" reaction and a titer showing a ≥
4-fold increase, routine repeat vaccinations or serosurveillance upon continued exposure to
the organism are not included in this protocol.

Inclusion Criteria:

1. Be 18 to 65 years old at time of consent.

2. 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).

3. Be considered at risk for exposure to Francisella tularensis (F tularensis) and who
have submitted a Request for IND Vaccines for the tularemia vaccine.

4. Sign and date the approved informed consent document and HIPAA Authorization.

5. Have in their charts:

1. medical history (including concomitant medications) within 60 days of planned
first administration of vaccine

2. physical examination and laboratory tests within 1 year

6. Be medically cleared for participation by an investigator. (Examinations and/or tests
may be repeated at the discretion of the principal investigator [PI].)

7. Be willing to return for all follow-up visits.

8. 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.

9. Agree to defer blood donation for 1 year after receipt of the vaccine.

Exclusion Criteria:

1. Have been vaccinated against tularemia or had a documented, confirmed tularemia
infection.

2. Have received antibiotic therapy within 7 days before vaccination.

3. Have clinically significant abnormal laboratory results (including evidence of
hepatitis C, hepatitis B carrier state) or elevated liver function tests (2 times the
normal range or at the discretion of the PI). All abnormal laboratory values will be
discussed with the research monitor and documented before a subject is enrolled in the
trial.

4. Have a personal history of an immunodeficiency, splenectomy 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.

5. Have confirmed HIV infection.

6. Have a positive pregnancy test or be a breastfeeding female.

7. Have any known allergies to components of the vaccine:

1. Live, attenuated Francisella tularensis

2. Modified casein partial hydrolysate (MCPH) broth

3. Glucose cysteine hemin agar (GCHA)

4. Sucrose Gelatin Agar Stabilizer

8. Have administration of blood products (such as blood transfusion, platelet
transfusion, immunoglobulin and/or hyperimmune serum), another vaccine or
investigational product within 28 days of tularemia vaccination.

9. Have any unresolved AE resulting from a previous immunization.

10. Have an acute or chronic medical condition (such as acute/chronic kidney disease,
pulmonary disease, metabolic disease, skin disease) that, in the judgment of the PI,
would impact subject safety.