A Study of Purified Inactivated Zika Virus Vaccine (PIZV) in Healthy Adults

A Randomized, Observer-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the Safety and Immunogenicity of the Purified Inactivated Zika Virus Vaccine (PIZV) Administered on Days 1 and 29 in Healthy Participants Aged 18 to 49 Years in the US

The purpose of this study is to describe the side effects and immune response of a candidate vaccine that might protect against Zika. The vaccine called PIZV (purified inactivated Zika virus vaccine) is given by injection in two doses that are 28 days apart in healthy adults. Participants will receive PIZV or placebo and will be followed for 7 days after each dose and up to 6 months after dose 2.

The candidate vaccine being tested in this study is called PIZV (purified inactivated zika virus vaccine) or TAK-426. This study will look at the safety and immunogenicity of PIZV in healthy participants.

The study will enroll approximately 78 healthy participants (≥18 to 49 years) following a 2-dose vaccination schedule. Participants will be randomly assigned (by chance, like flipping a coin) in a 2:1 ratio to either PIZV or placebo which will remain undisclosed to the study observer during the study:

• PIZV
• Placebo

Participants will receive PIZV or placebo 0.5 mL intramuscular (IM) injection into the middle third of the deltoid muscle, preferably in the non-dominant arm on Days 1 (Visit 1) and 29 (Visit 3). The seropositivity rate, seroconversion rate, and geometric-mean titers will be measured 28 days post dose 2. Solicited local reactions and systemic adverse events (AEs) will be assessed for 7 days after each vaccination. Unsolicited AEs will be assessed for 28 days after each vaccination and serious AEs (SAEs), AEs of special interest (AESIs), medically-attended AEs (MAAEs), and AEs leading to withdrawal from the trial throughout the entire study period.

This multi-center trial will be conducted in the United States (US). Trial participants will be in this study for 7 months.

Inclusion Criteria:

1. Healthy participants.
2. Participants who can comply with trial procedures (including new trial technologies) and are available for the duration of follow-up.
3. All females of childbearing potential must have a negative urine beta human chorionic gonadotropin (β-hCG) pregnancy test prior to receiving any dose.

Exclusion Criteria:

1. Participants with past or current ZIKV infection by self-report.

2. Participants with past or current dengue virus, yellow fever virus, Japanese encephalitis virus, tick-borne encephalitis virus or West Nile virus infection by self-report.

   Participants who have travelled to dengue and/or Zika endemic countries and US regions and territories*, or who plan to travel to these countries/regions within 1 month prior to anticipated enrollment up to 1 month post dose 2.

   *Centers for Disease Control and Prevention (CDC) website describes dengue/Zika endemic countries and US regions and territories.

3. Participants with any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).

4. Participants with known or suspected impairment/alteration of immune function, including:

   1. Chronic use of oral or 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 (use of inhaled, intranasal, or topical corticosteroids is allowed).
   2. Receipt of immunomodulatory agents within 60 days prior to Day 1.
   3. 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 receipt during the full length of the trial. In addition, participants must be advised not to donate blood during the study period.
   4. Known Human Immunodeficiency Virus (HIV) infection or HIV-related disease.
   5. Genetic immunodeficiency.

5. Participants with known current or chronic hepatitis B and/or hepatitis C infections.

6. Participants with abnormalities of splenic or thymic function.

7. Participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.

8. Participants with any serious chronic or progressive disease according to the judgment of the investigator (e.g., neoplasm, insulin-dependent diabetes, cardiac, renal, hepatic or thyroid disease, uncontrolled hypertension, uncontrolled asthma).

9. Participants with a history of substance or alcohol abuse within the past 2 years.