ZIKA Vaccine in Naive Subjects

Trial end date:
Target enrollment:
Participant gender:
This study is a study to evaluate the safety of ZPIV. Three dose levels may be evaluated. The entire duration of each subject's participation is approximately 14 months including recruitment and collection of data on the safety and reactogenicity of the study vaccine and samples for the assessment of immunogenicity. This study is expected to take approximately 30 months to complete from initiation through availability of a final report on the primary outcomes of safety and the secondary outcomes of humoral immunity to ZIKV. The Primary objectives of this study are to 1. Assess the safety and reactogenicity of a homologous prime boost regimen of ZPIV given at three different dose levels and 2. Compare the safety and reactogenicity profile of ZPIV after each vaccination and between dosage groups.
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Inclusion Criteria:

1. Must be a male or non-pregnant, non-breastfeeding female between the age 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 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/m^2

6. Must have acceptable* screening laboratory findings within 28 days before enrollment

- Acceptable clinical laboratory parameters include:

- Hemoglobin: women: >11.5 g/dL; men >12.5 g/d

- White blood cell count: >3,400 cells/mm^3 but <11,000 cells/mm^3

- Platelets: >139,000 but <450,000 per mm^3

- Urine dipstick (clean urine sample): protein <1+, glucose negative

- Serum creatinine
- Blood urea nitrogen (BUN) <25

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <1.25 x
institutional ULN

- Total bilirubin <1.25 x institutional ULN

- Note: If laboratory screening tests are out of acceptable range, repeat of
screening tests is permitted once, 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 exclusion criteria, it cannot meet
any of the following criteria: 1) first diagnosed in last 3 months , 2) worsening in terms
of clinical outcome in last 6 months; or 3) involves need for medication that may pose a
risk to subject's safety or impede assessment of adverse events or immunogenicity if they
participate in 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 serum 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 sterilized 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), OR

- 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), OR

- Male sex partners must have had a vasectomy >/=3 months prior to first vaccination, OR

- Practice abstinence defined as refraining from heterosexual intercourse from 30 days
before first vaccination until at least 60 days after 2nd 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 vaccination 11. Subjects must
provide concurrent consent at the time of enrollment and 1st vaccination to future use
of stored blood samples to measure immunity to ZIKV

Exclusion Criteria:

1. Has plans to become pregnant during the course of the study, or is currently pregnant
or breastfeeding.

2. Has plans to travel to an area with active Zika virus, DENV, YFV or JEV transmission*
during the study or returned from travel to an area with active transmission* within
30 days of screening.

* NOTE: Refer to CDC website for areas with active Zika, DENV, YFV, or JEV virus
transmission: http://www.cdc.gov

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:

- Yellow Fever virus (YFV): YF-VAX, Stamaril, or Bio-Manguinhos YF vaccine

- Japanese encephalitis virus (JEV): investigational vaccine or licensed
vaccine (IXIARO)

- Dengue virus (DENV): investigational vaccine or Sanofi Pasteur newly
licensed vaccine

- West Nile virus (WNV): investigational vaccine

- Zika virus (ZIKV)

- Other: St. Louis encephalitis, or tick-borne encephalitis virus (TBEV)

4. Plans to receive a licensed flavivirus vaccine or participate in another flavivirus
vaccine trial during the study.

5. Has positive serology to DENV, ZIKV, YFV, or WNV*.

- Serologic tests must be performed within 60 days of enrollment

6. Has positive serology for HIV 1/2, Hepatitis C virus, or Hepatitis B surface antigen*.

- Serologic tests must be performed within 60 days of enrollment

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.

8. Had organ and/or stem cell transplantation whether or not on chronic immunosuppressive

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 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 history of Guillain-Barre syndrome, seizure disorder or epilepsy,
Bell's palsy, meningitis, or disease with any focal neurologic deficits

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 last 12 months that in the investigator's opinion
would preclude participation.

14. Has history of other chronic disease or condition*

- Includes the conditions and diagnoses defined as AESI in section 9, as well as
autoimmune disease, hypercholesterolemia, chronic hepatitis or cirrhosis, chronic
pulmonary disease, chronic renal disease, and chronic cardiac disease including
hypertension even if medically controlled

- 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

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 the deltoid areas that would, in the opinion of
the investigator, interfere with assessment of the vaccination site(s)

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*.

- Including aluminum hydroxide (alum) or aminoglycosides (e.g., neomycin and

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
planned 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 until 14 days after
the last vaccination.

24. 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.

25. Is currently participating or plans to participate in another clinical study involving
an investigational product, blood drawing, or an invasive procedure listed below*.

- An invasive procedure requiring administration of anesthetics or intravenous dyes
or removal of tissue would be excluded. This includes endoscopy, bronchoscopy, or
administration of IV contrast.

26. Has an acute illness or temperature >/=38.0ÂșC on Day 1 or Day 29* or within 2days

- Subjects with fever or an acute illness on the day of vaccination or in the 2
days prior to vaccination may be re-assessed and enrolled if healthy or only
minor residual symptoms remain within 2 days of Day 1 or Day 29.

27. Is a study site employee* or staff paid entirely or partially by the OCRR contract for
the trial, or staff who are supervised by the PI or Sub-Investigators.

- Including the Principal Investigator, sub-Investigators listed in Form FDA 1572
or Investigator of Record Form

28. In the investigator's opinion, the subject cannot communicate reliably, is unlikely to
adhere to the study requirements, or has a condition that would limit their ability to
complete the study.