Safety and Immunogenicity of Prime-Boost VSV Ebola Vaccine in Healthy Adults

Between 1994 and the present, there have been many Ebola viruses (EBOV) outbreaks affecting
mostly central Africa. However, the 2014 West African outbreak significantly exceeds all
previous outbreaks in geographic range, number of individuals affected and in disruption of
typical activities of civil society.

This is a Phase 1 safety and tolerability study to evaluate a novel vaccine to Ebola using a
live replicating vesicular stomatitis virus (VSV) replacing the gene encoding the G envelope
glycoprotein with the gene encoding the envelope glycoprotein from the Zaire strain of Ebola
(VSVDG-ZEBOV also known as BPSC1001).

Healthy subjects will be screened for conditions that put the subject or others at risk from
the modified virus that is used as the vaccine vector. Those that qualify will be randomized
to receive VSVDG-ZEBOV or normal saline placebo as an intramuscular injection on Days 0 and
28, and evaluated on Study Days 3, 7, 14, 28, 31, 35, 42, 56, 84, 180, and 365. Using a
series of stopping rules and reviews from the Sponsor Medical Monitor, 3 cohorts of
increasing vaccine doses will be sequentially enrolled.

- INCLUSION CRITERIA:

- Healthy male or females, ages 18 to 65 (inclusive) at the time of screening

- Females of childbearing potential and all males, must be willing to use effective
methods of contraception, from at least 14 days prior to vaccination through Day 56
which would include:

- Oral contraceptives, either combined or progestogen alone

- injectable progestogen

- implants of etonogestrel or levonorgestrel

- oestrogenic vaginal ring

- percutaneous contraceptive patches

- intrauterine device or intrauterine system

- male partner sterilization

- male condom combined with a spermicide

- Must be willing to minimize blood and body fluid exposure of others for at least 7
days after vaccination, which includes:

- Use of effective barrier prophylaxis, such as latex condoms, during any sexual
interaction (regardless of childbearing status or sexual orientation)

- Avoiding the sharing of needles, razors, eating utensils, drinking from the same
cup, or toothbrushes

- Avoiding open-mouth kissing

- Must be willing to forgo blood donation for one year

- Must agree not to enroll in another study of an investigational agent prior to
completion of Day 56 and not participate in an investigational vaccine study until
the last required protocol visit on Day 365

- Ability to provide informed consent

EXCLUSION CRITERIA:

FACTORS THAT INCREASE RISK TO THE SUBJECT:

- Clinically significant medical condition, physical examination findings, clinically
significant abnormal laboratory results, or past medical history with clinically
significant implications for current health. A clinically significant condition or
process includes but is not limited to:

- A process that would affect the immune response

- A process that would require medication that affects the immune response

- Any contraindication to repeated injections or blood draws

- A condition that requires active medical intervention or monitoring to avert
grave danger to the participant s health or well-being during the study period

- A condition or process for which signs or symptoms could be confused with
reactions to vaccine

- Any condition specifically listed among the exclusion criteria below

- Active malignancy

- Asplenia

- History of Guillain-Barr(SqrRoot)(Copyright) Syndrome

- History of neurological or neuropsychiatric disorder that may either increase
risk (history of encephalitis, narcolepsy, stroke, depression, bipolar disorder,
seizure, etc.) or could interfere with the assessment of safety (e.g., frequent
headaches)

- History of autoimmune disease

- History of hemoglobinopathy or a coagulopathy

- Women who are breast-feeding

- Positive urine or serum pregnancy test

- Abnormal chemistry panel; defined as:

- Defined as any Grade 3 or greater toxicity (regardless of clinical significance)
by the toxicity table

- Evaluating only creatinine, ALT, AST, total bilirubin, and estimated GFR

- Abnormal complete blood count (CBC) defined as:

- Defined as any Grade 3 or greater toxicity (regardless of clinical significance)
by the toxicity table

- Evaluating only the WBC, hemoglobin, hematocrit, and platelets

- Abnormal urinalysis defined as:

- Defined as any Grade 3 or greater toxicity (regardless of clinical significance)
by the toxicity table

- Evaluating RBC, protein, and glucose only

- Positive serology for hepatitis B surface antigen

- Positive serology for hepatitis C

- Positive serology for HIV

- Known allergy to the components of the VSVDG-ZEBOV vaccine (BPSC1001) vaccine product
(VSV, albumin, tris)

- History of severe local or systemic reactions to any vaccination or a history of
severe allergic reactions

FACTORS THAT MAY LIMIT VSB REPLICATION OR MAKE INTERPRETATION OF IMMUNOGENICITY DIFFICULT:

- History of prior infection with a filovirus or prior participation in a filovirus
vaccine trial

- Veterinarian or ranchers exposed to livestock known to be infected with VSV

- History of prior infection with VSV or receipt of a VSV vectored vaccine

FACTOR THAT WOULD INCREASE RISK TO OTHERS DUE TO VSB VIRAL SHEDDING:

- Is a healthcare worker who will have direct contact with patients within 14 days of
each vaccination

- Is an animal care worker, who will have direct contact with animals (livestock or
domestic, besides subjects family pet) within 14 days of each vaccination

- Has a house-hold contact (HHC) who is immunodeficient (in the opinion of the
investigator), pregnant, has an unstable medical condition, or is under the age of 5
years

- Is a childcare worker who has direct contact with children 5 years of age or younger

FACTORS THAT COULD IMPAIR INTERPRETATION OR EXECUTION OF THE STUDY:

- Receipt of any investigational drug within 5 half lives or 30 days, whichever is
longer, prior to study drug administration (i.e., Day 0)

- Receipt of licensed vaccines 14 days before the planned study immunization

- Receipt of immunoglobulins and/or any blood products within the 120 days preceding
study entry or that are planned during the study period

- Immunosuppressive medications received within 168 days before first vaccination. (Not
including: [1] corticosteroid nasal spray for allergic rhinitis; [2] topical
corticosteroids for mild, uncomplicated dermatitis; or [3] oral/parenteral
corticosteroids given for non-chronic conditions not expected to recur [length of
therapy 10 days or less with completion at least 30 days prior to vaccination(s)].)

- Allergy treatment with antigen injections within 30 days before first vaccination or
that are scheduled through Day 56

- Participants who, in the judgment of the investigator, will be unlikely to comply
with the requirements of this protocol