| Eligibility |
Inclusion Criteria:
1. Must be a male or non-pregnant, non-breastfeeding female between the ages of 18 and 49
years, inclusive, at the time of screening and enrollment.
2. Must be willing and able to read, sign, and date the informed consent document before
study-related procedures are performed.
3. Must be willing and able to comply with study requirements and be available for
follow-up visits for the entire study.
4. Must have a means to be contacted by telephone.
5. Must have a body mass index (BMI) >/=18.1 and <35.0 kg/m2.
6. Must have acceptable screening laboratory findings within 40 days before day 1.
- Acceptable clinical laboratory parameters include no more than Grade 1 on
toxicity scale.
- White Blood Cell (WBC), Hemoglobin, and platelet count will be reported as part
of the Complete Blood Count (CBC). These labs will be graded according to the
toxicity scale. Other results included on the CBC panel will not be graded. They
will be reviewed by an investigator who will determine clinical significance and
may be used to determine additional workup.
- Sodium, potassium, blood urea nitrogen (BUN), creatinine, random glucose, total
protein, albumin, calcium, AST, ALT, total bilirubin, and alkaline phosphatase
will be reported as part of the Complete Metabolic Panel (CMP). These labs will
be graded according to the toxicity scale. Other results included on the CMP
panel will not be graded. They will be reviewed by an investigator who will
determine clinical significance and may be used to determine additional workup.
Note: If laboratory screening tests are out of acceptable range, repeat of screening
tests is permitted one time, provided there is an alternative explanation for the out
of range value.
7. Must be in good health based on the investigator's clinical judgment when considering
findings from past medical history, medication use, vital signs, and an abbreviated
physical examination.
Note 1: Good health is defined by the absence of any medical condition described in
the exclusion criteria in a subject with a normal abbreviated physical exam and vital
signs. If the subject has a preexisting condition not listed in the exclusion
criteria, the condition cannot meet any of the following criteria: first diagnosed in
the last 3 months; worsening in terms of clinical outcome in the last 6 months; or
involves need for medication that may pose a risk to the subject's safety or impede
assessment of AEs or immunogenicity if they participate in the study.
Note 2: An abbreviated physical exam differs from a complete exam in that it does not
include a genitourinary and rectal exam.
Note 3: Vital signs must be normal by protocol toxicity grading scale or determined to
be normal-variant by investigator. In the event of an abnormal heart rate or blood
pressure due to physiological variation or activity, the subject may rest for 10
minutes in a quiet room, and then blood pressure and/or heart rate may be re-measured.
Repeated vital signs may be used to determine eligibility.
8. Women of childbearing potential must have a negative urine pregnancy test at screening
and a negative urine pregnancy test immediately prior to each vaccination.
Note: All female subjects are considered of childbearing potential unless
postmenopausal or surgically sterile and >/=3 months have passed since sterilization
procedure. Postmenopausal is defined as amenorrhea for >/=12 months without an
alternative medical cause. Permanent female sterilization procedures include tubal
ligation, bilateral salpingectomy, hysterectomy, bilateral oophorectomy, or successful
Essure placement.
9. Women of childbearing potential must use an acceptable method of contraception from
one month (30 days) prior to the first vaccination until at least 60 days after the
last vaccination.
- Acceptable methods of contraception include the following: Use highly effective
contraceptive methods, defined by <1% failure rate per year independent of user
adherence, including long-acting reversible contraception (LARC):
progestin-releasing subdermal implants and intrauterine devices (IUD). Use
effective contraceptive methods, defined by 5-9% failure rate with typical use
and <1% failure rate with consistent and correct use, including: prescription
oral contraceptives, contraceptive injections, combined pill, progestin-only
pill, hormone-releasing transdermal patch or vaginal ring, and depot
medroxyprogesterone acetate injection (Depo-Provera). Have one male sex partner
who has had a vasectomy >/=3 months prior. Male partner with barrier protection
plus the use of vaginal spermicide. Practice abstinence defined as refraining
from heterosexual intercourse from 30 days before first vaccination until at
least 60 days after last ZPIV vaccination.
10. Female subjects must agree to not donate eggs (ova, oocytes) from the start of
screening period until at least 60 days after receiving the last ZPIV vaccination.
Exclusion Criteria:
1. Has plans to become pregnant, or is currently pregnant or breastfeeding.
2. Has plans to travel to an area with active ZIKV, DENV, YFV, or JEV transmission during
the study or returned from an endemic area with these diseases within 30 days of
screening.
NOTE: Refer to Centers for Disease Control and Prevention (CDC) website for areas with
active ZIKV transmission: http://www.cdc.gov/zika/geo
3. Has history of vaccination with a licensed or investigational flavivirus vaccine or
reportedly diagnosed with a flavivirus infection or disease. Includes subject's verbal
history of vaccination or disease with any of the following flaviviruses:
- YFV: YF-VAX®, Stamaril, or Bio-Manguinhos YF vaccine;
- JEV: investigational vaccine or licensed vaccine (IXIARO®);
- DENV: investigational vaccine or Sanofi Pasteur newly licensed vaccine;
- WNV: investigational vaccine;
- ZIKV;
- Other: St. Louis encephalitis, or TBEV.
4. Plans to receive a licensed flavivirus vaccine or participate in another flavivirus
vaccine trial during the study.
5. Seropositive to DENV, ZIKV, YFV, JEV, or WNV by microneutralization (MN) titer assay.
- Positive results may be repeated if technical error is suspected. Additional
testing to confirm Zika exposure and any required reporting or counseling will be
referred to the appropriate medical clinic.
6. Confirmed positive for active infection of human immounodeficiency virus (HIV),
hepatitis C virus (HCV), or presence of Hepatitis B surface antigen.
7. Has known or suspected congenital or acquired immunodeficiency, or recent history or
current use of immunosuppressive therapy.
- Anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or
long-term (at least 2 weeks within the previous 3 months) systemic
corticosteroids therapy (at a dose of at least 0.5 mg/kg/day). Intranasal or
topical prednisone (or equivalent) is allowed. Includes medication which, in the
opinion of the investigators(s), will impact the subject's immune response.
8. History of organ and/or stem cell transplantation.
9. Has history of malignancy other than squamous cell or basal cell skin cancer, unless
there has been surgical excision that is considered to have achieved a cure.
- Subjects with a history of skin cancer must not be vaccinated at the previous
tumor site.
10. Has history of chronic or acute severe neurologic condition.
- Including: Neurologic and Neuroinflammatory Disorders: ADEM, including site
specific variants, Cranial Nerve Disorders (including paralyses/paresis), GBS
(including Miller Fisher Syndrome and other variants), Immune-mediated Peripheral
Neuropathies and Plexopathies, Optic Neuritis, Multiple Sclerosis, Narcolepsy,
Transverse Myelitis, meningitis, or meningoencephalitis.
11. Has diabetes mellitus type 1 or type 2, including cases controlled with diet alone.
Note: history of isolated gestational diabetes is not an exclusion criterion.
12. Has history of thyroidectomy or thyroid disease requiring medication during the last
12 months.
13. Has major psychiatric illness during the last 12 months that in the investigator's
opinion would preclude participation.
14. Has history of other chronic disease or condition including:
- autoimmune disease, hypercholesterolemia, chronic hepatitis or cirrhosis, chronic
pulmonary disease, chronic renal disease, and chronic cardiac disease including
hypertension even if medically controlled.
- Includes the conditions and diagnoses defined as AESI in Section 9.
- Vital signs must be normal by protocol toxicity grading scale or determined to be
normal-variant by investigator. In the event of an abnormal heart rate or blood
pressure due to physiological variation or activity, the subject may rest for 10
minutes in a quiet room, and then blood pressure and/or heart rate may be
re-measured. Repeated vital signs may be used to determine eligibility.
15. Has current or past history of substance abuse that in the investigator's opinion
would preclude participation.
16. Has tattoos, scars, or other marks on both deltoid areas that would, in the opinion of
the investigator, interfere with assessment of the vaccination site.
17. Has a history of chronic urticaria (recurrent hives).
18. Has known allergy or history of anaphylaxis, or other serious reaction to a vaccine or
vaccine component. - Note: includes protamine sulfate, eggs or egg products, chicken
protein, gelatin, sorbitol, aminoglycosides (e.g., neomycin and streptomycin), or any
of the constituents of the study vaccines including alum.
19. Had major surgery (per the investigator's judgment) in the month prior to screening or
plans to have major surgery during the study.
20. Received blood products or immunoglobulin in the 3 months prior to screening or plans
to use during the course of the study.
21. Donated a unit of blood within 8 weeks before Day 1 or plans to donate blood during
the course of the study.
22. Received live attenuated vaccine from 30 days before Day 1 until 30 days after the
last vaccination.
23. Received killed or inactivated vaccine from 14 days before Day 1 and until 14 days
after the last vaccination.
- Note: Subjects may receive inactivated seasonal influenza vaccine 14 days prior or
30 days after each study vaccination (JEV, YFV, or ZPIV).
24. Severe allergy or anaphylaxis to latex.
25. Received experimental therapeutic agents within 3 months prior to the first study
vaccination or plans to receive any experimental therapeutic agents during the course
of the study.
26. History of thymus disorder including myasthenia gravis, thymoma, or prior thymectomy.
27. Is currently participating or plans to participate in another clinical study that
involves:
- An investigational product, blood drawing, or an invasive procedure requiring
administration of anesthetics or intravenous (IV) dyes or removal of tissue. This
includes endoscopy, bronchoscopy, or administration of IV contrast.
28. Has an acute illness or temperature >/=38.0 ºC on any vaccination (ZPIV and priming
vaccinations) or within 48 hours of planned vaccination.
- Subjects with fever or an acute illness on the day of vaccination or in the 3
days prior to vaccination may be re-assessed and enrolled.
29. In the investigator's opinion, the subject cannot communicate reliably, is unlikely to
adhere to study requirements, or has a condition that would limit his or her ability
to complete the study.
30. Is unwilling to have their samples collected and stored for future research.
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