Clinical Trial: 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

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

Official Title: Phase I, Randomized, Double-blinded, Placebo-Controlled Dose De-escalation Study to Evaluate the Safety and Immunogenicity of Alum Adjuvanted Zika Virus Purified Inactivated Vaccine (ZPIV) Administere

Brief 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 42 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.

Detailed Summary: This study is a single-center, randomized, double-blinded, placebo-controlled, Phase 1, dose de-escalation study to evaluate the safety, reactogenicity, and immunogenicity of a purified inactivated, alum-adjuvanted ZIKV vaccine (ZPIV) administered in a homologous prime-boost regimen to healthy male and non-pregnant female adult subjects living in a flavivirus-endemic area. 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 entire duration of each subject's participation is approximately 26 months including recruitment and collection of data on the safety and reactogenicity of the study vaccine and collection of samples for the assessment of immunogenicity. This study is expected to take approximately 42 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. 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 homologous boost on Day 29, and a follow-up period of 24 months post boost vaccination. The study will begin with enrollment of 2 sentinel subjects in Group 1 who will receive 5 mcg ZPIV open label. One sentinel subject will be vaccinated, followed for one day for safety and reactogenicity, and if no halting rules are met per determination of the PI and co-PI, then the second sentinel subject will receive 5 mcg ZPIV open-label. Both sentinels will be followed for safety through Day 8 and if no predefined halting rules are met and no safety concerns are identified, then enrollment of the remaining 43 Group 1 subjects will proceed in double-blind fashion. The same procedure will be used for administration of the boost vaccination to the Group 1 sentinels: 1 sent
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Comparison of study withdrawals and discontinuation of study vaccination due to any reason between dosage groups and by pre-vaccination flavivirus immune status [ Time Frame: Days 1 to 750 ]
  • Comparison of the duration of vaccine-related Grade 3 local, systemic, or laboratory AE, and Grade 2 or greater local or systemic reactogenicity between dosage groups and by pre-vaccination flavivirus immune status [ Time Frame: Days 1 to 8 ]
  • Comparison of the duration of vaccine-related Grade 3 local, systemic, or laboratory AE, and Grade 2 or greater local or systemic reactogenicity between dosage groups and by pre-vaccination flavivirus immune status [ Time Frame: Days 29 to 36 ]
  • Comparison of the frequency of vaccine-related Grade 3 local, systemic, or laboratory AE, and Grade 2 or greater local or systemic reactogenicity between dosage groups and by pre-vaccination flavivirus immune status [ Time Frame: Days 1 to 8 ]
  • Comparison of the frequency of vaccine-related Grade 3 local, systemic, or laboratory AE, and Grade 2 or greater local or systemic reactogenicity between dosage groups and by pre-vaccination flavivirus immune status [ Time Frame: Days 29 to 36 ]
  • Comparison of the type of vaccine-related Grade 3 local, systemic, or laboratory AE, and Grade 2 or greater local or systemic reactogenicity between dosage groups and by pre-vaccination flavivirus immune status [ Time Frame: Days 1 to 8 ]
  • Comparison of the type of vaccine-related Grade 3 local, systemic, or laboratory AE, and Grade 2 or greater local or systemic reactogenicity between dosage groups and by pre-vaccination flavivir

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Frequency of seroconversion to ZIKV measured by neutralization assay in comparison with baseline sample [ Time Frame: Time Frame: Days 1, 15, 29, 43, 57, 210, 388, 569, 750 ]
    • Frequency of seroconversion to ZIKV measured by ZIKV ELISA in comparison with baseline sample [ Time Frame: Days 1, 15, 29, 43, 57, 210, 388, 569, 750 ]
    • Peak GMT as measured by neutralization assay [ Time Frame: Days 1, 15, 29, 43, 57, 210, 388, 569, 750 ]
    • Peak GMT as measured by ZIKV ELISA [ Time Frame: Days 1, 15, 29, 43, 57, 210, 388, 569, 750 ]
    • Per Visit GMT as measured by neutralization assay [ Time Frame: Days 1, 15, 29, 43, 57, 210, 388, 569, 750 ]
    • Per Visit GMT as measured by ZIKV ELISA [ Time Frame: Days 1, 15, 29, 43, 57, 210, 388, 569, 750 ]
    • Proportion of subjects with at least a 4-fold rise in ZIKV GMT as measured by ZIKV ELISA and neutralization assay compared with baseline overall [ Time Frame: Days 29 to 57 ]


    Original Secondary Outcome: Same as current

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

    Dates:
    Date Received: December 15, 2016
    Date Started: February 24, 2017
    Date Completion: January 15, 2020
    Last Updated: March 30, 2017
    Last Verified: March 16, 2017