Safety, Tolerability, and Immunogenicity of the COVID-19 Vaccine Candidates VBI-2902a and VBI-2905a
Condition: Covid19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 1

Summary: 
      VBI-2902a and VBI-2905a are investigational vaccine candidates that use enveloped virus-like
      particle (eVLP) expression of a modified version of the SARS-CoV-2 spike (S) glycoprotein and
      are designed to induce neutralizing antibody and cell-mediated immune responses against the
      SARS-CoV-2 spike protein. VBI-2902a expresses the spike protein of SARS-CoV-2 Wuhan isolate
      (the first virus variant isolated in 2019 in Wuhan, China), while VBI-2905a expresses the
      spike protein of SARS-CoV-2 variant Beta (B.1.351 variant, first isolated in 2020 in South
      Africa).

      The Phase 1a portion of this study tests one- and two-dose regimens of VBI- 2902a with 5 μg S
      protein content and aluminum phosphate (alum) adjuvant or placebo delivered by intramuscular
      (IM) injection. The Phase 1b portion of the study tests a one-dose regimen of VBI-2905a with
      5 μg S protein content and alum adjuvant or placebo delivered by IM injection in participants
      previously vaccinated with an authorized mRNA COVID-19 vaccine.
    

Detailed description: 
      Phase 1a:

      The primary objective is to evaluate the safety and tolerability of VBI-2902a containing 5 μg
      of S protein in one- or two-dose regimens in healthy adults of 18-54 years of age.

      The secondary objective is to evaluate the immunogenicity of VBI-2902a containing 5 μg of S
      protein in one- or two-dose regimens in healthy adults 18-54 years of age.

        -  Group G1 - 20 participants will receive VBI-2902a at a dose of 5 μg of S protein at Day
           1 and placebo at Day 28.

        -  Group G2 - 20 participants will receive VBI-2902a at a dose of 5 μg of S protein at Days
           1 and 28.

        -  Group G3 - 20 participants will receive placebo at Days 1 and 28.

      An Independent Data Safety Monitoring Board (DSMB) will review blinded safety data
      (reactogenicity, adverse events (AEs) and safety laboratory assessments) at Day 7 after the
      first vaccination. The second vaccination will only be given if the DSMB confirms that Day 7
      safety is acceptable and that stopping rules were not met. The DSMB will further review
      blinded post-vaccination safety through Day 35, 7 days after the second vaccination and
      through Day 56, 28 days after the second vaccination. The study will be unblinded following
      DSMB review of safety data collected through Day 56. Study participants will continue with
      study visits as planned up to 12 months of follow up after the first dose of study vaccine.

      Phase 1b:

      The primary objective is to evaluate the safety and tolerability of a one-dose regimen of
      VBI-2905a at a 5 μg dose level of S protein in healthy adults (age 18-54 years) who had been
      previously vaccinated with mRNA vaccines.

      The secondary objective is to evaluate the immunogenicity of a one-dose regimen of VBI-2905a
      at a 5 μg dose level of S protein in healthy adults (age 18-54 years) who had been previously
      vaccinated with mRNA vaccines.

      A total of 54 healthy adults, age 18-54 years, with no history of clinical or laboratory
      diagnosis of SARS-CoV- 2 infection or COVID-19 illness, will be enrolled in the Phase 1b part
      of the study. All participants in Phase 1b will have been previously vaccinated with an
      authorized mRNA COVID-19 vaccine, including the second dose administered at least 4 months
      prior to enrollment, will be randomized at a 1:1 ratio to receive, in a blinded fashion, one
      dose of VBI-2905a or placebo:

        -  Group G4 - 27 participants will receive VBI-2905a at a dose of 5 μg of S protein at Day
           1

        -  Group G5 - 27 participants will receive placebo at Day 1

      The DSMB will review blinded post-vaccination safety data 7 days after each vaccination
      (reactogenicity, AEs and safety laboratory assessments). In Phase 1b, the DSMB will review
      blinded Day 7 safety data after the first 10 participants in groups G4 and G5 have received
      the first dose. Only after the DSMB confirms that safety is acceptable and that stopping
      rules were not met will the enrollment in the respective study groups continue to its
      completion.
    

Intervention name(s): VBI-2902a; Placebo; VBI-2905a
Intervention type(s): Biological; Biological; Biological
Intervention description(s): VBI-2902a is an intramuscular injection of VBI-2902a investigational enveloped virus-like particle COVID-19 vaccine with aluminum phosphate adjuvant.; 0.9% sodium chloride; VBI-2905a is an intramuscular injection of VBI-2905a investigational enveloped virus-like particle COVID-19 vaccine with aluminum phosphate adjuvant.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: enveloped virus-like particle (eVLP); SARS-CoV-2 spike; neutralizing antibody; cell-mediated immune responses