Experimental Ebola Vaccine Trial
Experimental Ebola Vaccine Trial
This study will test the safety of an experimental vaccine developed to protect against Ebola
 virus infection and to determine if the vaccine induces an immune response to the virus. The
 Ebola virus causes a disease called Ebola hemorrhagic fever. Symptoms begin with fever and
 muscle aches and progress to breathing problems, severe bleeding, kidney problems, and shock.
 The infection may be mild, but it can also lead to death. The vaccine used in this study is
 made from small parts of Ebola genetic material. It cannot cause Ebola hemorrhagic fever to
 develop in those who receive it.

 Healthy volunteers 18 to 44 years of age may be eligible for this study. Candidates will be
 screened with a medical history, physical examination, and laboratory tests, and complete an
 "assessment of understanding" questionnaire to show that they understand the study.

 Depending on their order of entry into the study, participants are assigned to receive one of
 three vaccine doses or placebo. The first group receives the lowest dose (2 milligram) of
 vaccine or placebo. If this dose is safe, then the second group receives 4 mg, and if this
 dose is safe, the third group receives 8 mg. Injections are given in a muscle in the upper
 arm. Participants receive three injections, each 4 weeks apart (on study days 0, 28, and 56).

 Participants record their temperature and symptoms in a diary card for 7 days following each
 injection. They return to the clinic 2 to 3 days after each injection and then 2 weeks after
 each injection until study week 10. Additional follow-up visits are then scheduled at weeks
 12, 24, 38, and 52. At each visit, participants provide a blood and urine sample for testing
 and have their vital signs, and lymph nodes checked, their weight measured, and their
 symptoms reviewed. Additional laboratory tests may be requested between visits.
This is a Phase I, randomized, placebo-controlled, dose-escalation study of an Ebola DNA
 plasmid vaccine. The hypothesis is that the vaccine will be safe for human administration and
 elicit immune responses to Ebola. Primary objectives are to evaluate the safety and
 tolerability of the investigational vaccine and the secondary objective is to evaluate immune
 responses. Randomization assignment will be blinded to subjects, clinical investigators and
 laboratory investigators.
-  INCLUSION CRITERIA:

 A volunteer must meet all of the following inclusion criteria:

 1. 18 to 44 years old.

 2. Available for follow-up for the duration of the study (12 months).

 3. Able to provide proof of identity to the acceptance of the study clinician completing
 the enrollment process.

 4. Completion of an Assessment of Understanding prior to enrollment and verbalize
 understanding of all questions answered incorrectly.

 5. Able and willing to complete the informed consent process.

 6. Willing to receive HIV test results and willing to abide by NIH guidelines for partner
 notification of positive HIV results.

 7. Willing to donate blood for sample storage.

 8. In good general health without clinically significant medical history.

 9. Physical examination and laboratory results without clinically significant findings
 within the 28 days prior to enrollment.

 Laboratory Criteria within 28 days prior to enrollment:

 10. Hematocrit equal to 34% for women; 38% for men.

 11. Normal fibrinogen levels, D-dimer immunoassay less than 2.0 microg/mL, and RBC
 morphology without evidence of microangiopathic hemolysis.

 12. WBC count: Non-African Americans: equal to 3,300-12,000 cells/mm3, African-Americans:
 equal to 2,500 - 12,000 cells/mm3 (in the absence of clinical or pathological
 etiology).

 13. Differential either within institutional normal range or accompanied by site physician
 approval.

 14. Total lymphocyte count: Non-African Americans: equal to 800 cells/mm3, African
 Americans: equal to 650 cells/mm3 (in the absence of clinical or pathological
 etiology)

 15. Platelets within institutional normal limits.

 16. Prothrombin time and activated partial thromboplastin time (PT, PTT) within
 institutional normal range.

 17. Alanine aminotransferase (ALT) (also called SGPT) = upper limit of normal range

 18. Serum creatinine = upper limit of normal range

 19. Negative Food and Drug Administration (FDA)-approved HIV blood test

 20. Negative hepatitis B surface antigen (HbsAg)

 21. Negative antibody to hepatitis C virus (anti-HCV), or negative HCV PCR if the anti-HCV
 is positive.

 22. Normal urinalysis defined as negative glucose, negative or trace protein, and negative
 hemoglobin by dipstick.

 Female-Specific Criteria:

 23. Negative pregnancy test (urine or serum) for women presumed to be of reproductive
 potential.

 24. A female participant must meet one of the following criteria:

 No reproductive potential because of menopause (one year without menses) or because of a
 hysterectomy, bilateral oophorectomy, or tubal ligation,

 or

 Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and
 throughout the duration of the study,

 or

 Participant agrees to consistently practice contraception at least 21 days prior to
 enrollment and throughout the duration of the study by one of the following methods:

 -  condoms, male or female, with or without a spermicide

 -  diaphragm or cervical cap with spermicide

 -  intrauterine device

 -  contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved
 contraceptive method

 -  male partner has previously undergone a vasectomy for which there is documentation

 EXCLUSION CRITERIA:

 A volunteer will be excluded if one or more of the following conditions apply.

 Women:

 1. Breast-feeding.

 Volunteer has received any of the following substances:

 2. Immunosuppressive or cytotoxic medications within the past six months with the
 exception of corticosteroid nasal spray for allergic rhinitis or topical
 corticosteroids for an acute uncomplicated dermatitis

 3. Blood products within 120 days prior to HIV screening.

 4. Immunoglobulin within 60 days prior to HIV screening.

 5. Live attenuated vaccines within 30 days prior to initial study injection.

 6. Investigational research agents within 30 days prior to initial study injection.

 7. Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or
 allergy treatment with antigen injections, within 14 days prior to initial study
 injection.

 8. Current anti-TB prophylaxis or therapy.

 Volunteer has a history of any of the following clinically significant conditions:

 9. Serious adverse reactions to vaccines, such as anaphylaxis, hives, respiratory
 difficulty, angioedema, or abdominal pain.

 10. Autoimmune disease or immunodeficiency.

 11. Asthma that is unstable or required emergent care, urgent care, hospitalization or
 intubation during the past two years or that requires the use of oral or intravenous
 corticosteroids.

 12. Diabetes mellitus (type I or II), with the exception of gestational diabetes.

 13. Thyroid disease including history of thyroidectomy and diagnoses that required
 medication within the past 12 months.

 14. Serious angioedema episodes within the previous 3 years or requiring medication in the
 previous two years.

 15. Hypertension that is not well controlled by medication or is more than 145/95 at
 enrollment.

 16. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or
 platelet disorder requiring special precautions) or significant bruising or bleeding
 difficulties with IM injections or blood draws.

 17. Malignancy that is active or treated malignancy for which there is not reasonable
 assurance of sustained cure or malignancy that is likely to recur during the period of
 the study.

 18. Seizure disorder other than: 1) febrile seizures under the age of two, 2) seizures
 secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not
 requiring treatment within the last 3 years.

 19. Asplenia or any condition resulting in the absence or removal of the spleen.

 20. Psychiatric condition that precludes compliance with the protocol; past or present
 psychoses; past or present bipolar disorder requiring therapy that has not been well
 controlled by medication for the past two years; disorder requiring lithium; or
 suicidal ideation occurring within five years prior to enrollment

 21. Any medical, psychiatric, or social condition, or occupational or other responsibility
 that, in the judgment of the investigator, would interfere with or serve as a
 contraindication to protocol adherence or a volunteer's ability to give informed
 consent.