Placebo Controlled, Dose Response, Safety and Immunogenicity Study of 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
(VSVΔG-ZEBOV also known as BPSC-1001).

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 at one of four dose levels or normal saline placebo as an
intramuscular injection on Day 0, and evaluated on Study Days 1, 2, 3, 4, 7, 14, 28, 56, 84,
180, and 360. The study will be managed using a series of stopping rules and reviews by the
DSMB.

Subject Inclusion Criteria:

1. Healthy adult male or non-pregnant, non-lactating adult female, ages 18 to 60
(inclusive) at the time of screening

2. Have provided written informed consent prior to screening procedures

3. Free of clinically significant health problems, as determined by pertinent medical
history, physical examination and clinical judgement of the investigator.

4. Available, able, and willing to participate for all study visits and procedures.

5. Males and females who are willing to practice abstinence from sexual intercourse with
the opposite sex, or willing to use effective methods of contraception, from at least
30 days prior to vaccination until study end.

6. Be willing to minimize blood and body fluid exposure of others for 7 days after
vaccination by:

1. Using effective barrier prophylaxis, such as latex condoms, during penetrative
sexual intercourse

2. Avoiding the sharing of needles, razors, or toothbrushes

3. Avoiding open-mouth kissing

Subject Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

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

2. History of prior infection with VSV or receipt of a VSV vectored vaccine

3. Is a healthcare worker who has direct contact with patients (nurse, physician,
dentist, emergency medical technician, dental hygienist)

4. Has a house-hold contact (HHC) who is immunodeficient, on immunosuppressive
medications, HIV-positive, pregnant, has an unstable medical condition

5. Has an HHC, or is a childcare worker who has direct contact with children, 5 years of
age or younger

6. Direct hands-on job preparing food in the food industry

7. History of employment in an industry involved in contact with ruminant animals,
veterinary sciences, or other potential exposure to VSV

8. History of employment or activity which involves potential contact with filoviruses

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

10. Known allergy to the components of the BPSC1001 vaccine product

11. Receipt of investigational product up to 30 days prior to randomization or ongoing
participation in another clinical trial

12. Receipt of licensed non-live vaccines within 14 days of planned study immunization
(30 days for live vaccines)

13. Ability to observe possible local reactions at the eligible injections sites (deltoid
region) is, in the opinion of the investigator, unacceptably obscured due to a
physical condition or permanent body art

14. Acute or chronic, clinically significant psychiatric, hematologic, pulmonary,
cardiovascular, or hepatic or renal functional abnormality as determined by the
investigator based on medical history, physical examination, and/or laboratory
screening test. This would include a known hemoglobinopathy or coagulation
abnormality.

15. Any baseline laboratory screening test which in the opinion of the investigator, is
considered clinically significant

16. Any serologic evidence of hepatitis B or C infection

17. Any confirmed or suspected immunosuppressive or immunodeficient condition, including
HIV-1, HIV-2 infection, cytotoxic therapy in the previous 5 years, and/or diabetes

18. Any chronic or active neurologic disorder, including migraines, seizures, and
epilepsy, excluding a single febrile seizure as a child

19. Have a known history of GBS

20. Have an active malignancy or history of metastatic or hematologic malignancy

21. Suspected or known alcohol and/or illicit drug abuse within the past 5 years

22. Moderate or severe illness and/or fever >100.4°F within 1 week prior to vaccination
(subjects can be rescheduled)

23. Pregnant or lactating female, or female who intends to become pregnant during the
study period

24. Administration of IgGs and/or any blood products within the 120 days preceding study
entry or planned administration during the study period

25. History of blood donation within 60 days of enrollment or plans to donate within the
study period

26. Administration of chronic (defined as more than 14 days) immunosuppressants or other
immune modifying drugs within 6 months of study entry

1. For corticosteroids, this includes prednisone, or equivalent, greater than or
equal to 0.5 mg/kg/day

2. Intranasal, topical, and intra-articular steroids are allowed

27. Unwilling to allow storage and use of blood for future vaccine research

28. Research staff or the immediate family of research staff directly involved with the
clinical study.

29. Any other significant finding that in the opinion of the investigator would increase
the risk of the individual having an adverse outcome from participating in this study

30. Elective surgery or hospitalization planned during the period of study participation

31. Subject has traveled to an area where the WHO has declared as an Ebola outbreak zone