Phase 1 Trial of Inactivated West Nile Virus Vaccine
Phase 1 Trial of Inactivated West Nile Virus Vaccine
This trial will be a randomized, placebo controlled, double-blind (within dosing group), dose
 escalation phase 1 trial, evaluating dosages of 1 mcg and 4 mcg of HydroVax-001 WNV vaccine
 given intramuscularly on Day 1 and Day 29 in up to 50 healthy adults > /=18 and < 50 years of
 age. The primary objective is to assess the safety, reactogenicity, and tolerability of the
 HydroVax-001 WNV vaccine administered intramuscularly in a two-dose series on Days 1 and 29
 at a dose of 1 mcg or a dose of 4 mcg.
This trial will be a randomized, placebo controlled, double-blind (within dosing group), dose
 escalation phase 1 trial, evaluating dosages of 1 mcg and 4 mcg of HydroVax-001 WNV vaccine
 given intramuscularly on Day 1 and Day 29 in up to 50 healthy adults > /=18 and < 50 years of
 age at a single site. The study will consist of two dosing groups of HydroVax-001 vaccine to
 be enrolled sequentially. Each dose group will consist of 20 individuals who receive
 HydroVax-001 and 5 who receive placebo. Controls will receive sterile 0.9 percent NaCl
 placebo intramuscularly at days 1 and 29. The study duration is approximately 25 months (12
 month enrollment, 13 month follow up) and subject participation duration of approximately 14
 months. The primary objective is to assess the safety, reactogenicity, and tolerability of
 the HydroVax-001 WNV vaccine administered intramuscularly in a two-dose series on Days 1 and
 29 at a dose of 1 mcg or a dose of 4 mcg. The secondary objective is to assess WNV-specific
 plaque reduction neutralization test (PRNT50) responses after a first dose and after a second
 dose of HydroVax-001 WNV vaccine given at doses of 1 mcg and 4 mcg. This study aims to
 recruit up to 50 men and women between the ages of 18 and 50. The study duration is
 approximately 25 months at a single site and subject participation duration is approximately
 14 months.
Inclusion Criteria:

 1.Age >/=18 years and < 50 years 2.Able to read, sign, and date the informed consent
 document 3. Available and willing to participate for the planned duration of the study
 4.Are in good health, as judged by the investigator and determined by vital signs, medical
 history, and physical examination 5.Sexually active males must agree to use a medically
 acceptable form of contraception* in order to be in this study and must agree to continue
 such use until day 30 after the last vaccination.Medically acceptable contraceptives
 include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a
 spermicide. Contraceptive measures such as Plan B (TM), sold for emergency use after
 unprotected sex, are not acceptable methods for routine use. 6.Women of childbearing
 potential* must have a negative serum pregnancy test at screening and a negative urine
 pregnancy test within 24 hours prior to each vaccination *Not sterilized via tubal
 ligation, bilateral oophorectomy, or hysterectomy and still menstruating or < 1 year of the
 last menses if menopausal 7. Women of childbearing potential must have used an acceptable
 method of contraception* in the 30 days prior to enrollment and must agree to continue such
 use until day 30 after the last vaccination. *Includes, but is not limited to, abstinence
 from sex with men,barrier methods such as condoms or diaphragms with spermicide or foam,
 effective intrauterine devices, NuvaRing®, successful Essure® placement (permanent,
 non-surgical, non-hormonal sterilization) with documented confirmation test at least 3
 months after the procedure, and licensed hormonal methods such as implants, injectables, or
 oral contraceptives

 Exclusion Criteria:

 1. Any clinically significant acute or chronic medical condition* or need for chronic
 medications** that, in the opinion of the investigator, will interfere with immunity or
 affect safety *Includes, but is not limited to, disorders of the liver, kidney, lung,
 heart, or nervous system, or other metabolic or autoimmune/inflammatory conditions **
 Receipt of systemic, prescription medications for the treatment of chronic medical
 conditions or variations of normal physiologic functions are permissible if, in the opinion
 of the investigator, they are used for conditions that are not clinically significant and
 would not impact the safety of the subject or the safety and immunogenicity outcomes of the
 protocol. Use of systemic, over-the-counter medications and PRN systemic, prescription
 medication are allowed if, in the opinion of the investigator, they pose no additional risk
 to subject safety or assessment of immunogenicity/reactogenicity. Topical (except
 corticosteroid) medications, nasal (including corticosteroid) medications, vitamins, and
 supplements are permissible 2. Asthma, other than mild, well-controlled asthma* *Cold or
 exercise induced asthma controlled with inhaled medications other than inhaled
 corticosteroids is permissible. Participants should be excluded if they require daily
 bronchodilator use, or have had an asthma exacerbation requiring oral/parenteral steroid
 use or have used theophylline or inhaled corticosteroids in the past year 3. Diabetes
 mellitus 4. Unstable depression or bipolar disorder* *Has received <3 months of the same
 anti-depressant or bipolar disorder medication(s) (and dose) or has had a decompensating
 event during the previous 3 months or has depression or bipolar disorder that in the
 opinion of the investigator will compromise the subject's ability to comply with protocol
 requirements 5. Unstable seizure disorder (defined as requiring medication for seizure
 control or with seizure activity within the past 3 years) 6. Autoimmune disease (lupus,
 multiple sclerosis, rheumatoid arthritis, autoimmune thyroid disease, etc.); vitiligo, and
 mild eczema or mild psoriasis not requiring chronic therapy are permissible. 7. Known or
 suspected congenital or acquired immunodeficiency including anatomic or functional asplenia
 or immunosupppression as a result of underlying illness or treatment 8. Abuse of alcohol or
 drugs that, in the opinion of the investigator, may interfere with the subject's ability to
 comply with the protocol 9. Unstable hypertension (well-controlled hypertension with
 medication is permissible) 10. Body mass index (BMI) >/= 35 11. Known allergy to components
 of the study product .Including the following: aluminum hydroxide, sorbitol, potassium
 chloride, sodium chloride 12. Seropositive to West Nile virus 13. History of a visit to
 South America or sub-Saharan Africa lasting one month or more 14. History of military
 service 15. History of vaccination against yellow fever, tick-borne encephalitis, or
 Japanese encephalitis 16. History of vaccination with West Nile virus candidate vaccines.
 17. Attended primary (grade) school in Austria, Germany, Japan, South Korea, India,
 Thailand, Nepal, Vietnam, or Taiwan (where tick-borne encephalitis vaccine is given) 18.
 History of dengue fever or receipt of a dengue fever vaccine 19. Active neoplastic disease*
 *Participants with a history of malignancy may be included if treated by surgical excision
 or if treated by chemotherapy or radiation therapy has been observed for a period that in
 the investigator's estimation provides a reasonable assurance of sustained cure (not less
 than 36 months) 20. Chronic topical or systemic corticoste roid use* *Corticosteroid nasal
 sprays for allergic rhinitis are permissible. Persons using a topical corticosteroid for a
 limited duration for mild uncomplicated dermatitis such as poison ivy or contact dermatitis
 may be enrolled the day after their therapy is completed. Oral or parenteral (intravenous,
 subcutaneous or intramuscular) corticosteroids given for non-chronic conditions not
 expected to recur are permissible if, within the year prior to enrollment, the longest
 course of therapy was no more than 14 days and no oral or parenteral corticosteroids were
 given within 30 days prior to enrollment. Intraarticular, bursal, tendon, or epidural
 injections of corticosteroids are permissible if the most recent injection was at least 30
 days prior to enrollment. 21. Are breastfeeding or plan to breastfeed at any time
 throughout the study 22. Receipt or planned receipt of inactivated vaccine or allergy
 desensitization injection 14 days before or after a study vaccination 23. Receipt or
 planned receipt of live attenuated vaccine 30 days before or after a study vaccination 24.
 Receipt of any other experimental agent within 30 days prior to vaccination or planned
 receipt prior to the end of the study 25. Plans to enroll in another clinical trial* that
 could interfere with safety assessment of the investigational product at any time during
 the study period *Includes trials that have a study intervention such as a drug, biologic,
 or device 26 Receipt of blood products or immunoglobulin within six months prior enrollment
 27. Donation of a unit of blood within 56 days prior to enrollment or intends to donate
 blood during the study period 28. Systolic blood pressure >140 mm Hg or diastolic blood
 pressure >90 mm Hg 29.Resting heart rate <40 or >100 beats per minute 30.Oral temperature
 >/= 38 degrees C (100.4 degrees F) 31.Positive serology for HIV 1/2* *If the enzyme linked
 immunosorbent assay (ELISA) is positive, HIV confirmation should be performed. If the HIV
 Western Blot is not consistent with HIV infection, the volunteer may be enrolled. A past
 participant in an HIV vaccine trial who has a positive antibody ELISA may participate if
 the Western Blot is not consistent with pending seroconversion or positive or an HIV
 polymerase chain reaction (PCR) assay result is below the level of detection of HIV. 32.
 Positive hepatitis B surface antigen (HBsAg) 33. Positive antibody to hepatitis C virus
 (HCV) 34. Any Grade 1 or higher screening clinical lab value* (see Toxicity Table Appendix
 B) *Screening clinical labs include blood tests (white blood cell [WBC] count, hemoglobin
 level, platelet count, creatinine, blood urea nitrogen, non-fasting glucose, potassium,
 alanine aminotransferase [ALT], aspartate aminotransferase [AST], and total bilirubin) and
 urine tests (protein, glucose). 35. Plan to have a major change in exercise routine from 72
 hours before any dose of study vaccine/placebo through 15 days after that dose 36. Acute
 febrile illness (oral temperature >/= 38 deg