A Phase 1, First-in-human, Double-blinded, Randomized, Placebo-controlled Trial of a Zika Virus Purified Inactivated Vaccine (ZPIV) With Alum Adjuvant in Healthy Flavivirus-naive and Flavivirus-Primed Subjects.
Condition: Zika Virus Infection
MeSH terms: Zika Virus Infection
Study type: Interventional
Phase: Phase 1

Summary: 
      Phase 1 study to evaluate two doses of Alum Adjuvanted Zika Virus Purified Inactivated
      Vaccine (ZPIV) administered 28 days apart. The study will enroll 75 flavivirus naïve healthy
      adult subjects into 3 equal groups sequentially. Each group will include 20 ZPIV recipients
      and 5 placebo recipients. Group 1 will receive two ZPIV or placebo doses 28 days apart. Those
      in Group 1 who consent to a third ZPIV dose will receive 5.0 mcg dose of ZPIV or placebo
      administered IM on Day 224. Group 2 subjects will receive a two-dose regimen of IXIARO® 28
      days apart; two ZPIV or placebo doses three months later 28 days apart. Those in Group 2 who
      consent to a third ZPIV dose will receive it on Day 336. Group 3 subjects will receive one
      dose of YF-VAX® followed three months later by two ZPIV or placebo doses 28 days apart. Those
      in Group 3 who consent to a third ZPIV dose will receive it on Day 308. In each group, those
      who do not agree to receive the third ZPIV dose will be followed based on the schedule. The
      primary objectives are: 1) To evaluate the safety and reactogenicity of a two-dose homologous
      prime boost regimen of ZPIV among flavivirus-naïve, YF-VAX® primed, and IXIARO® primed
      subjects; 2) To evaluate the safety and reactogenicity of a third dose of ZPIV in consenting
      subjects.
    

Detailed description: 
      This study is a single-center, double-blinded, placebo-controlled, first-in-human, Phase 1
      study to evaluate the safety, reactogenicity, and immunogenicity of two doses of alum
      adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) administered 28 days apart. The
      study will enroll 75 flavivirus naïve healthy male and non-pregnant, non-breastfeeding female
      adult subjects (ages 18-49, inclusive) into 3 equal groups sequentially, starting with Group
      1 followed by Group 2 and then Group 3. Screening will occur within 40 days of first
      vaccination. Each group will include 20 ZPIV recipients and 5 placebo recipients. Two
      sentinel subjects from Group 1 will be enrolled first and will receive ZPIV in an open-label
      fashion first. The next 23 subjects (18 ZPIV, 5 placebo) will be randomized into Group 1.
      This will be followed by the randomization of 25 subjects into Group 2 (JE priming). The
      remaining 25 subjects to enroll will be randomized into Group 3 (YF priming). Group 1
      subjects will receive two 5.0 mcg doses of ZPIV or placebo administered IM on Days 1 and 29.
      Those in Group 1 who consent to a third ZPIV dose will receive 5.0 mcg dose of ZPIV or
      placebo administered IM on Day 224. Group 2 subjects will receive a two-dose regimen of
      IXIARO® (Valneva) 28 days apart; two ZPIV or placebo doses will be administered three months
      later IM 28 days apart. Those in Group 2 who consent to a third ZPIV dose will receive it on
      Day 336. Group 3 subjects will receive one dose of YF-VAX® (Sanofi Pasteur) followed three
      months later by two ZPIV or placebo doses administered IM 28 days apart. Those in Group 3 who
      consent to a third ZPIV dose will receive it on Day 308. In each group, those who do not
      agree to receive the third ZPIV dose will be followed based on the schedule. The primary
      objectives are: 1) To evaluate the safety and reactogenicity of a two-dose homologous prime
      boost regimen of ZPIV among flavivirus-naïve, YF-VAX® primed, and IXIARO® primed subjects; 2)
      To evaluate the safety and reactogenicity of a third dose of ZPIV in consenting subjects. The
      secondary objectives are: 1) To evaluate the quantitative humoral immune response at 28 days
      after the first and second ZPIV administration, and 112, 196, 280, and 364 days after the
      first ZPIV administration for each of the three groups in subjects who consent to two doses
      of ZPIV; 2) To evaluate the quantitative humoral immune response at 28 days after the first
      and second ZPIV administration, and 112, 196, 224 days after the first ZPIV administration
      and at 28, 84, and 168 days after the third ZPIV administration for Group 1 subjects who
      consent to third dose; 3) To evaluate the quantitative humoral immune response at 28 days
      after the first and second ZPIV administration, and 112, 224 days after the first ZPIV
      administration and at 28, 84, and 168 days after the third ZPIV administration for Group 2
      and 3 subjects who consent to third dose.
    

Intervention name(s): IXIARO; Placebo; YF Vax 17D Strain; Zika Virus Purified Inactivated Vaccine (ZPIV)
Intervention type(s): Biological; Other; Biological; Biological
Intervention description(s): An inactivated vaccine indicated for active immunization for the prevention of disease caused by Japanese encephalitis virus (JEV).; 0.9% Sodium Chloride 5 mcg; A stabilised Yellow Fever Vaccine (Live) that is an injectable suspension of the attenuated 17D strain of yellow fever virus. The vaccine is injected by the subcutaneous route.; Zika Virus Purified Inactivated Vaccine with aluminum hydroxide adjuvant.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Adjuvant; Alum; Inactivated; Purified; Vaccine; Virus; Zika