Evaluate the Safety, Immunogenicity and Potential Efficacy of an rVSV-SARS-CoV-2-S Vaccine
Condition: Covid19
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The SARS-CoV-2 virus is responsible for the COVID-19 pandemic. The pandemic emerged from
      Wuhan Province in China in December 2019 and was declared by the WHO Director-General a
      Public Health Emergency of International Concern on 30 January 2020.

      In this study, a vaccine developed by IIBR for SARS-CoV-2 virus will be assessed for its
      safety and potential efficacy in volunteers. The study is comprised of two phases, a
      dose-escalation phase (phase I) during which subjects (18-55 years old) will be randomly
      allocated to receive a single administration of IIBR-100 at low, mid or high dose or saline
      or two administrations of IIBR-100 at low dose, or saline, 28 days apart.

      Based on results obtained during phase I, and cumulative phase I data review, the expansion
      phase (phase II) has begun, during which larger cohorts as well as elderly age subjects were
      initially planned to be randomly allocated to receive a single administration of IIBR-100 at
      low, mid or high dose or saline, or two administrations of IIBR-100 at low, mid or high dose
      (prime-boost) or saline, 28 days apart. Additional top-dose (prime-boost) may be implemented
      when immunogenicity of any prime-boost arm is considered insufficient. However, based on
      immunogenicity preliminary data and DSMB recommendations, only the two administrations of
      mid, high and top dose (prime-boost) or saline will continue in the study.

      The subjects will be followed for a period of up to 12 months post last vaccine
      administration to assess the safety and efficacy of the vaccine.
    

Detailed description: 
      In the Phase I, healthy adult volunteers will be randomly allocated to one of the four
      treatment groups to receive a single administration (prime) of IIBR-100 at low, mid or high
      dose or saline or two administrations (prime-boost) of IIBR-100 at low dose, or saline, 28
      days apart. During Phase I, dosing of prime will proceed in a sequential fashion followed by
      a safety review committee and DSMB to consider expansion to include the rest of the group and
      escalation to the next groups. Only Groups that demonstrate acceptable safety profile,
      immunogenicity and potential efficacy will be included in the Phase II operation. In both
      phases, the subjects will receive an intramuscular injection of the IIBR-100 consisted of 1ml
      replicating viral rVSV SARS-CoV-2-S vaccine or placebo consisted of 1ml of 0.9% saline.
      Dosing will be performed at Day 0 and Day 28 (for allocated to prime-boost treatment groups)
      in the deltoid muscle and will be followed through 12 months post last vaccination. Follow-up
      visits for subjects administered with the single administration (prime) or placebo will occur
      at 1, 2 and 4 weeks as well as 2, 3, 6, 9 and 12 months after dosing. Follow up visits for
      subjects administered with two administrations (prime-boost) or placebo will occur at 1, 2
      and 4 weeks post each vaccination as well as at 2, 3, 6, 9 and 12 months after the second
      vaccination. Reactogenicity will be measured by the occurrence of solicited injection site
      and systemic reactions from the time of each dosing through 7 days post each dosing.
      Unsolicited non-serious safety events will be collected from the time of each dosing through
      28 days post each dosing. Serious safety events, new-onset chronic medical conditions and
      medically attended safety events will be collected through 12 months after the last dosing.
    

Intervention name(s): IIBR-100, low dose (prime); IIBR-100 medium dose (prime); IIBR-100 high-dose (prime); IIBR-100 low-dose (prime-boost); Saline Placebo (single); Saline Placebo (double); IIBR-100 medium-dose (prime-boost); IIBR-100 high-dose (prime-boost); IIBR-100 top-dose (prime-boost)
Intervention type(s): Biological; Biological; Biological; Biological; Other; Other; Biological; Biological; Biological
Intervention description(s): Single administration of IIBR-100 1*10E5 pfu/ml; Single administration of IIBR-100 1*10E6 pfu/ml; Single administration of IIBR-100 1*10E7 pfu/ml; Two administrations of IIBR-100 1*10E5 pfu/ml, 28 days apart; Single administration of saline placebo; Two administrations of saline placebo, 28 days apart; Two administrations of IIBR-100 1*10E6 pfu/ml, 28 days apart; Two administrations of IIBR-100 1*10E7 pfu/ml, 28 days apart; Two administrations of IIBR-100 1*10E8 pfu/ml, 28 days apart
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: The study is comprised of two phases, a dose-escalation Phase I (sentinels + expansions) and expansion to Phase II that includes larger cohorts, elderly age groups and additional boost injection. Subjects will be randomly allocated to the study groups in both phases.
Dosing of prime during phase I occurred in a sequential fashion (partially overlapping), starting from low-dose and continuing to mid and high doses following safety reviews. Prior to expansion to phase II, cumulative data from phase I was evaluated (dose and regimen) by the data safety monitoring board. The DSMB's recommendations regarding expansion to phase II were the continuation of prime-boost regimens of medium, high and top doses.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: SARS-CoV-2; Vaccine