Clinical Trial: 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.

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 1, First-in-Human, Double-blinded, Randomized, Placebo-controlled Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of an Alum Adjuvanted Zika Virus Purified Inactivated Vaccine

Brief 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. 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. Group 3 subjects will receive one dose of YF-VAX® followed three months later by two ZPIV or placebo doses 28 days apart. A subset of up to 30 will be selected to receive a third ZPIV vaccination. 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 a subset of up to 30 subjects.

Detailed Summary: 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 ZPIV administered 28 days apart. The study will enroll 75 flavivirus naïve healthy male and non-pregnant female, non-breastfeeding 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 28 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). Each group will include 20 ZPIV recipients and 5 placebo recipients. Group 1 subjects will receive two 5.0 mcg doses of ZPIV or placebo administered IM on Days 1 and 29. 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. 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. A subset of up to 30 subjects (10 subjects per group) will be selected to receive a third ZPIV vaccination. 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 a subset of up to 30 subjects (10 per group). The secondary objectives are: 1) To evaluate the quantitative humoral immune response at 28 days after the first and secon
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Occurrence and severity of solicited local AEs [ Time Frame: 7 days following each ZPIV dose ]
  • Occurrence and severity of solicited systemic AEs [ Time Frame: 7 days following each ZPIV dose ]
  • Occurrence of SAEs, new onset medical conditions, and AESIs [ Time Frame: From Day 1 to Day 658 ]
  • Occurrence, severity, and relationship to vaccination of unsolicited AEs [ Time Frame: 28 days following each ZPIV dose ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Anti- ZIKV NAbs GMTs for the subset of up to 30 subjects [ Time Frame: Days 28, 84 and 168 after third ZPIV dose ]
  • Anti- ZIKV NAbs GMTs overall and by group [ Time Frame: 28 days after each ZPIV dose and days 112, 196, 280 and 364 after initial ZPIV dose ]
  • Anti- ZIKV NAbs seroconversion for the subset of up to 30 subjects [ Time Frame: Days 28, 84 and 168 after third ZPIV dose ]
  • Anti- ZIKV NAbs seroconversion rates overall and by group [ Time Frame: 28 days after each ZPIV dose and days 112, 196, 280 and 364 after initial ZPIV dose ]


Original Secondary Outcome: Same as current

Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: November 10, 2016
Date Started: November 1, 2016
Date Completion:
Last Updated: March 30, 2017
Last Verified: November 4, 2016