Clinical Trial: ZIKA Vaccine in Naive Subjects

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

Official Title: Phase 1, Double-blinded, Placebo-Controlled Dose De-escalation Study of the Safety and Immunogenicity of Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) Administered by the Intramuscula

Brief Summary: This study is a dose de-escalation study to evaluate the safety of ZPIV. Three dose levels may be evaluated. The entire duration of each subject's participation is approximately 14 months including recruitment and collection of data on the safety and reactogenicity of the study vaccine and samples for the assessment of immunogenicity. This study is expected to take approximately 30 months to complete from initiation through availability of a final report on the primary outcomes of safety and the secondary outcomes of humoral immunity to ZIKV. The Primary objectives of this study are to 1. Assess the safety and reactogenicity of a homologous prime boost regimen of ZPIV given at three different dose levels in a dose de-escalation format, and 2. Compare the safety and reactogenicity profile of ZPIV after each vaccination and between dosage groups.

Detailed Summary: This study is a single-center, double-blinded, placebo-controlled, Phase 1, dose de-escalation study to evaluate the safety, reactogenicity, and immunogenicity of ZPIV administered in a homologous prime-boost regimen to Flavivirus-naïve healthy male and non-pregnant female adult subjects. Three dose levels may be evaluated. Each subject will receive either placebo or 5.0 mcg (high dose [HD]), 2.5 mcg (moderate dose [MD]), or 1.25 mcg (low dose [LD]) of ZPIV administered by intramuscular (IM) injection on Days 1 and 29. 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 12 months post boost vaccination. The entire duration of each subject's participation is approximately 14 months including recruitment and collection of data on the safety and reactogenicity of the study vaccine and samples for the assessment of immunogenicity. This study is expected to take approximately 30 months to complete from initiation through availability of a final report on the primary outcomes of safety and the secondary outcomes of humoral immunity to ZIKV. The Primary objectives of this study are to 1. Assess the safety and reactogenicity of a homologous prime boost regimen of ZPIV given at three different dose levels in a dose de-escalation format, and 2. Compare the safety and reactogenicity profile of ZPIV after each vaccination and between dosage groups. The secondary objectives of this study are to 1. Assess the humoral immune response overall and by dosage group to a homologous prime-boost regimen of ZPIV as determined by kinetics of the immune responses, seroconversion rates, and peak Geometric Mean Titer (GMT) and to 2. Assess the durability of the humoral immune response overall and by dosage group to ZPIV at 6 and 12 months after the second vaccine administration.
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Comparison between dosage groups of the duration of vaccine-related Grade 2 or greater local or systemic reactogenicity [ Time Frame: 8 Days after each vaccination ]
  • Comparison between dosage groups of the duration overall and in each dosage group of vaccine-related Grade 3 local, systemic, or laboratory AE [ Time Frame: 8 Days after each vaccination ]
  • Comparison between dosage groups of the frequency of vaccine-related Grade 2 or greater local or systemic reactogenicity [ Time Frame: 8 Days after each vaccination ]
  • Comparison between dosage groups of the frequency of vaccine-related Grade 3 local, systemic, or laboratory AE [ Time Frame: 8 Days after each vaccination ]
  • Comparison between dosage groups of the type of vaccine-related Grade 2 or greater local or systemic reactogenicity [ Time Frame: 8 Days after each vaccination ]
  • Comparison between dosage groups of the type overall and each dosage group of vaccine-related Grade 3 local, systemic, or laboratory AE [ Time Frame: 8 Days after each vaccination ]
  • Comparison of study withdrawals, and discontinuation of study vaccination due to any reason between dosage groups. [ Time Frame: 14 Months ]
  • Duration overall and in each dosage group of serious adverse events (SAE) and adverse events of special interest (AESI) considered related to study vaccination [ Time Frame: 14 Months ]
  • Frequency of new onset chronic medical conditions [ Time Frame: 14 Months ]
  • Frequency over

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Peak GMT overall and by dosage group as measured by ZIKV ELISA and neutralization assay. [ Time Frame: At all post-vaccination visits, an average of 14 months ]
    • Per visit GMT overall and by dosage group as measured by ZIKV ELISA and neutralization assay. [ Time Frame: At all post-vaccination visits, an average of 14 months ]
    • Proportion of subjects overall and by dosage group that seroconvert to ZIKV at each post-vaccination visit by assessing ELISA responses in comparison with baseline [ Time Frame: At all post-vaccination visits, an average of 14 months ]
    • Proportion of subjects overall and by dosage group that seroconvert to ZIKV at each post-vaccination visit by assessing neutralization titers in comparison with baseline [ Time Frame: At all post-vaccination visits, an average of 14 months ]


    Original Secondary Outcome: Same as current

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

    Dates:
    Date Received: October 13, 2016
    Date Started: October 14, 2016
    Date Completion: February 5, 2018
    Last Updated: April 6, 2017
    Last Verified: April 5, 2017