Safety, Immunogenicity, and Dose Ranging Study of Inactivated Zika Virus Vaccine in Healthy Participants
Condition: Virus, Zika; Zika Virus Disease; Flavivirus Infections; Healthy Participants
MeSH terms: Virus Diseases; Zika Virus Infection; Flavivirus Infections
Intervention: Placebo; PIZV
Intervention description: Placebo (normal saline (0.9% NaCl) IM injection.; Purified inactivated Zika virus vaccine with aluminum hydroxide adjuvant IM injection.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Enrollment: 271.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug therapy

Summary:

      The purpose of this study is to describe the safety, tolerability and immunogenicity of two
      doses of purified inactivated Zika virus vaccine (PIZV) given 28 days apart. Three different
      vaccine doses containing different protein concentrations (2, 5 or 10 microgram [mcg]) each,
      will be given as 2 dose schedule to flavivirus naive and primed healthy adults. Participants
      will be followed for 7 days post each dose for tolerability and up to 6 months post dose 2
      for safety. Immunogenicity assessment will be performed at 28 days post each dose and 6
      months post dose 2. In addition, the selected dose group and control group will be followed
      till 24 months post dose 2 for safety and persistence of immunity.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participants who are in good health at the time of entry into the trial as determined
             by medical history, physical examination (including vital signs) and eligibility
             screening tests (hematology, biochemistry and urinalysis) and clinical judgment of the
             investigator. Vital signs must be within normal limits (ie, below Grade 1 as specified
             in the Food and Drug Administration [FDA] Toxicity Grading Scale for Healthy Adult and
             Adolescent Volunteers). Screening tests must be within normal limits or not be above
             Grade 1 as defined in the FDA Toxicity Grading Scale for Healthy Adult and Adolescent
             Volunteers.

          2. Participants who can comply with trial procedures and are available for the duration
             of follow-up.

          3. All female participants must be willing to undergo serum beta human chorionic
             gonadotropin (B-hCG) pregnancy test and must test negative by urine pregnancy test
             prior to each study vaccination.

        Exclusion Criteria:

          1. Participants and participants' partners with confirmed Zika virus (ZIKV) infection by
             self-report.

          2. Traveling to flavivirus endemic countries or flavivirus endemic regions of the United
             States (US) or US territories*, within 4 weeks prior to screening or planned travel
             through to Visit 6 (applicable only to participants to be enrolled into the flavivirus
             naïve cohort).

             a. Centers for Disease Control and Prevention (CDC) website define the information
             about the flavivirus endemic countries and US regions and territories.

          3. Known hypersensitivity or allergy to any of the vaccine candidate components
             (including excipients of the investigational vaccine or placebo).

          4. Has any history of progressive or severe neurologic disorder, seizure disorder or
             neuro-inflammatory disease (example, Guillain-Barré syndrome).

          5. Known or suspected impairment/alteration of immune function, including:

               -  Chronic use of oral steroids (equivalent to 20 milligram per day [mg/day]
                  prednisone greater than or equal to [>=] 12 weeks / >= 2 milligram per kilogram
                  [mg/kg] body weight / day prednisone >= 2 weeks) within 60 days prior to Day 1
                  (use of inhaled, intranasal, or topical corticosteroids is allowed).

               -  Receipt of parenteral steroids (equivalent to 20 mg/day prednisone >= 12 weeks /
                  >= 2 mg/kg body weight / day prednisone >= 2 weeks) within 60 days prior to Day
                  1.

               -  Receipt of immunostimulants within 60 days prior to Day 1.

               -  Receipt of parenteral, epidural or intra-articular immunoglobulin preparation,
                  blood products, and/or plasma derived products within 3 months prior to Day 1 or
                  planned during the full length of the trial. In addition, participants must be
                  advised not to donate blood during the study period.

               -  Known Human Immunodeficiency Virus (HIV) infection or HIV-related disease.

               -  Genetic immunodeficiency.

          6. Has known current or chronic hepatitis B and/or hepatitis C infections.

          7. Has abnormalities of spleen or thymic function.

          8. Has a known bleeding diathesis, or any condition that may be associated with a
             prolonged bleeding time.

          9. Individuals participating in any clinical trial with another investigational product,
             including ZIKV vaccine clinical trial within 30 days prior to first trial visit or
             intent to participate in another clinical trial at any time during the conduct of this
             trial.

         10. Individuals who received any other vaccines within 14 days (for inactivated vaccines)
             or 28 days (for live vaccines) prior to enrollment in this trial or who are planning
             to receive any vaccine within 28 days of investigational vaccine/placebo
             administration.

         11. Female participants who are pregnant or breastfeeding, or are planning to become
             pregnant.

         12. Any positive or indeterminate pregnancy test.

         13. If female participant of childbearing potential, sexually active, and who has not used
             any of the "acceptable contraceptive methods" for at least 2 months prior to trial
             entry:

               -  "Of childbearing potential" is defined as status post onset of menarche and not
                  meeting any of the following conditions: menopausal for at least 2 years without
                  any other alternative medical cause (as confirmed by a healthcare professional),
                  status after bilateral tubal ligation for at least 1 year, status after bilateral
                  oophorectomy, or status after hysterectomy.

               -  Acceptable birth control methods are defined as one or more of the following:

                    -  Hormonal contraceptive (such as oral, injection, transdermal patch, implant,
                       cervical ring).

                    -  Barrier (condom with spermicide or diaphragm with spermicide) each and every
                       time during intercourse.

                    -  Intrauterine device.

                    -  Monogamous relationship with vasectomized partner. Partner must have been
                       vasectomized for at least six months prior to the participants' trial entry.

         14. If female participant of childbearing potential and sexually active, refusal to use an
             "acceptable contraceptive method" from trial entry through 2 months after the last
             dose of investigational vaccine/placebo. In addition female participants of
             childbearing potential must be advised not to donate ova during this period.

         15. To avoid sexual transmission of ZIKV from natural exposure: Refusal to use latex
             condoms correctly and consistently by sexually active participants even if other
             contraceptive measures are used from signing the informed consent form (ICF) through
             the end of the trial. Male participants must be advised not to donate sperm during
             this period.