Phase I, Randomized, Double-blinded, Placebo-Controlled Dose De-escalation Study to Evaluate Safety and Immunogenicity of Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) in Adults in a Flavivirus Endemic Area
Condition: Zika Virus Infection
MeSH terms: Zika Virus Infection
Intervention: Placebo; Zika Virus Purified Inactivated Vaccine (ZPIV)
Intervention description: Placebo; Zika Virus Purified Inactivated Vaccine with aluminum hydroxide adjuvant.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 91.0
Sex: All
Minimum age: 21 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Flavivirus; Inactivated; Phase I; Vaccine; ZIKA; ZPIV

Summary:

      This study is randomized, double-blinded, placebo-controlled, Phase 1, dose de-escalation
      study to evaluate the safety, reactogenicity, and immunogenicity of Alum Adjuvanted Zika
      Virus Purified Inactivated Vaccine (ZPIV) administered to healthy male and non-pregnant
      female adult subjects. This study will enroll 90 healthy male and non-pregnant female
      subjects between the ages of 21 and 49 and will be conducted at Ponce Medical School
      Foundation, Inc.-CAIMED in Ponce, Puerto Rico. The duration of each subject's participation
      is approximately 26 months from recruitment through the last study visit. The entire study is
      expected to take approximately 49 months to complete. Two dose levels will be evaluated. Each
      subject will receive either placebo or 5 mcg (Group 1) or 2.5 mcg (Group 2) of ZPIV
      administered by intramuscular (IM) injection on Days 1 and 29. Solicited local and systemic
      reactogenicity data will be collected from all subjects through Day 8 after each vaccination.
      All subjects will be monitored for occurrence of unsolicited adverse events until 28 days
      after the second vaccination. The study will consist of a screening period of up to 28 days,
      a vaccination period in which subjects will receive a prime dose of vaccine on Day 1 followed
      by a boost on Day 29, and a follow-up period of 24 months post boost vaccination. Primary
      objectives are: 1) Assess the safety and reactogenicity of a homologous prime boost regimen
      of ZPIV given at two different dose levels. 2) Compare the safety and reactogenicity of ZPIV
      after each vaccination, between dosage groups, and by pre-vaccination flavivirus immune
      status.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Must be a male or non-pregnant, non-breastfeeding female between the age of 21 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/m2.

          6. Must have acceptable* screening laboratory findings within 28 days before enrollment.

               -  Acceptable clinical laboratory parameters include:

                    -  Hemoglobin: women: > /= 11.5 g/dL; men > /= 13.5 g/dL

                    -  Hemotocrit: women: > /= 34.5%; men > /= 40.5%

                    -  White blood cell count: > /= 3.500 cells/mm3 but < /= 10,800 cells/mm3

                    -  Platelets: > /= 150,000 but < /= 450,000 per mm3

                    -  Urine dipstick (clean urine sample): protein < 1+, glucose negative

                    -  Serum creatinine < /= 1 x institutional upper limit of normal (ULN)

                    -  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 the end of the study.

             *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 the end of the study.

         10. Female subjects must agree to not donate eggs (ova, oocytes) from the start of
             screening period until the end of the study.

         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. Plans to receive a licensed flavivirus vaccine or participate in another flavivirus
             vaccine trial during the study.

          3. Has positive serology for HIV 1/2, Hepatitis C virus, or Hepatitis B surface antigen.

          4. 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.

          5. Had organ and/or stem cell transplantation whether or not on chronic immunosuppressive
             therapy.

          6. 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.

          7. 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.

          8. 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.

          9. Has history of thyroidectomy, or thyroid disease requiring medication during the last
             12 months.

         10. Has major psychiatric illness during last 12 months that in the investigator's opinion
             would preclude participation.

         11. 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 eligibility.

         12. Has current or past history of substance abuse that in the investigator's opinion
             would preclude participation.

         13. 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.

         14. Has a history of chronic urticaria (recurrent hives).

         15. 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
             streptomycin).

         16. Had major surgery (per the investigator's judgment) in the month prior to screening or
             plans to have major surgery during the study.

         17. Received blood products or immunoglobulin in the 3 months prior to screening or
             planned use during the course of the study.

         18. Donated a unit of blood within 8 weeks before Day 1 or plans to donate blood during
             the course of the study.

         19. Received live attenuated vaccine from 30 days before Day 1 or plans to receive a live
             attenuated vaccine from Day 1 until 30 days after the last vaccination.

         20. Received killed or inactivated vaccine from 14 days before Day 1 or plans to receive a
             killed or inactivated vaccine from Day 1 until 14 days after the last vaccination.

         21. 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.

         22. 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.

         23. Has an acute illness or temperature > /= 38.0ºC on Day 1 or Day 29* or within 2 days
             prior to vaccination.

             *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.

         24. Is a study site employee* or staff paid entirely or partially by the OCRR contract or
             subcontract 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

         25. 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.