VBI-2901a is an investigational vaccine candidate that uses enveloped virus-like particles (eVLPs) to express the spike proteins of three coronaviruses: SARS-CoV-2 (the virus that causes COVID-19 disease), SARS-CoV-1 and MERS-CoV. The trivalent vaccine candidate is designed to induce neutralizing antibody and cell-mediated immune responses against the spike protein of the original strain of SARS-CoV-2, SARS-CoV-2 variants (such as Beta, Delta and Omicron) and other related coronaviruses that could emerge in the future. The Phase 1 study will be an open-label comparison of two intramuscular doses of VBI-2901a at 5 µg or 10 µg per dose or one dose of VBI-2901a at 10 µg per dose in adults 18 to 64 years of age who had previously received two or more vaccinations with licensed COVID-19 vaccines. The purpose of the study is to test the safety of VBI-2901a and to know more about its ability to boost immune response against SARS-CoV-2 (the virus that causes COVID-19 disease) and two other related coronaviruses SARS-CoV-1 and MERS-CoV.
VBI-2901a is an investigational trivalent COVID-19 vaccine candidate that comprises enveloped virus-like particles (eVLPs) expressing the spike proteins of the beta-coronaviruses SARS-CoV-2, SARS-CoV-1 and MERS-CoV. The study will enroll participants 18 to 64 years of age who have previously received two or more vaccinations with a licensed COVID-19 vaccine(s) and will test two intramuscular doses of VBI-2901a containing 5 µg or 10 µg of spike protein and one dose of VBI-2901a containing 10 µg of spike protein. VBI-2901a eVLPs are formulated with 0.33 mg of aluminum phosphate (alum) adjuvant per dose. VBI-2901a is designed to induce neutralizing antibody and cell-mediated immune responses against multiple coronavirus respiratory disease strains and variants of SARS-CoV-2. This is a randomized, open-label Phase 1 study. The study will enroll adults, aged 18 to 64 years, who are healthy or in stable health; had previously received two or more vaccinations with a licensed COVID-19 vaccine(s) with the final dose administered a minimum of 6 months (24 weeks) prior to enrollment; have a negative PCR or rapid antigen SARS-CoV-2 test at screening; and have met all other eligibility criteria. Participants with a history of mild COVID-19 illness are eligible if they fully recovered a minimum of 6 months (24 weeks) prior to enrollment. A total of 99 participants will be randomized at a 1:1:1 ratio to the following study groups: Group G1: 33 participants to receive two doses of VBI-2901a at 5 µg per dose at Day 1 and Day 56. Group G2: 33 participants to receive two doses of VBI-2901a at 10 µg per dose at Day 1 and Day 56. Group G3: 33 participants to receive one dose of VBI-2901a at 10 µg per dose at Day 1. The total study duration for each vaccinated subject is 48 weeks (336 days) after administration of the first dose of study vaccine. During the study, the participant will make 9 visits to the study site, including the screening visit. The objective of the study is to select the optimal dose level (5 µg or 10 µg) and number of doses (1 or 2 doses) of trivalent coronavirus vaccine candidate VBI-2901a in individuals who had been vaccinated against COVID-19 previously. To achieve this objective, the study will evaluate outcomes including safety and tolerability as well as antibody and T cell immune responses against SARS-CoV-2 ancestral (Wuhan) strain, selected SARS-CoV-2 variants, SARS-CoV-1 and MERS-CoV.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
103
Intramuscular injection of VBI-2901a, an investigational trivalent coronavirus vaccine that contains three coronavirus spike proteins with aluminum phosphate adjuvant.
Canadian Center for Vaccinology
Halifax, Nova Scotia, Canada
Red Maple Trials
Ottawa, Ontario, Canada
Ottawa Hospital
Ottawa, Ontario, Canada
LMC Manna - Bayview CPU
Toronto, Ontario, Canada
LMC Manna Toronto
Toronto, Ontario, Canada
Manna Research Inc
Pointe-Claire, Quebec, Canada
CHU de Québec Université Laval
Québec, Quebec, Canada
Local reactions (solicited adverse events) within 7 days of study vaccination
Time frame: Through 7 days after each vaccination
Systemic reactions (solicited adverse events) within 7 days of study vaccination
Time frame: Through 7 days after each vaccination
Unsolicited adverse events within 28 days of study vaccination
Time frame: Through 28 days after each vaccination
Serious adverse events within 28 days of study vaccination and end of study
Time frame: Through end of study (approximately 1 year)
Medically-attended adverse events within 28 days of study vaccination and end of study
Time frame: Through end of study (approximately 1 year)
Seroresponse rate against SARS-CoV-2 ancestral (Wuhan) strain
Percent of participants with ≥ 4-fold rise in neutralizing antibody titer at 28 days after the first vaccination and, in participants receiving two doses, 28 days after the second vaccination, compared to baseline (Day 1).
Time frame: Study days 1, 28 and 84
Seroresponse rate against SARS-CoV-2 variants of concern (Beta, Delta and Omicron)
Percent of participants with ≥ 4-fold rise in neutralizing antibody titer at 28 days after the first vaccination and, in participants receiving two doses, 28 days after the second vaccination, compared to baseline (Day 1).
Time frame: Study days 1, 28 and 84
Seroresponse rate against SARS-CoV-1 and MERS-CoV
Percent of participants with ≥ 4-fold rise in neutralizing antibody titer at 28 days after the first vaccination and, in participants receiving two doses, 28 days after the second vaccination, compared to baseline (Day 1).
Time frame: Study days 1, 28 and 84
Geometric mean titer (GMT) of SARS-CoV-2 neutralizing antibodies
Geometric mean titer of SARS-CoV-2 neutralizing antibodies against SARS-CoV-2 ancestral (Wuhan) strain and variants of concern (Beta, Delta and Omicron), SARS-CoV-1 and MERS-CoV at days 1, 7, 28, 56, 63, 84, 168 and 336.
Time frame: Study days 1, 7, 28, 56, 63, 84, 168 and 336
Geometric mean fold rise (GMFR) in serum neutralizing antibody titer against SARS-CoV-2 ancestral (Wuhan) strain and variants of concern (Beta, Delta and Omicron), SARS-CoV-1 and MERS-CoV
Geometric mean fold rise in serum neutralizing antibody titer against SARS-CoV-2 ancestral (Wuhan) strain and variants of concern (Beta, Delta and Omicron), SARS-CoV-1 and MERS-CoV at Days 7, 28, 56, 63, 84, 168 and 336 compared to baseline (Day 1).
Time frame: Study days 1, 7, 28, 56, 63, 84, 168 and 336
GMT and GMFR in serum IgG antibody to spike protein and receptor-binding-domain (RBD) against SARS-CoV-2 ancestral (Wuhan) strain, selected SARS-CoV-2 variants (Beta, Delta and Omicron), SARS-CoV-1 and MERS-CoV
GMT and GMFR in serum IgG antibody to spike protein and receptor-binding-domain (RBD) by enzyme-linked immunosorbent assay (ELISA) against SARS-CoV-2 ancestral (Wuhan) strain, selected SARS-CoV-2 variants (Beta, Delta and Omicron), SARS-CoV-1 and MERS-CoV at Days 7, 28, 56, 63, 84, 168, and 336 compared to baseline (Day 1)
Time frame: Study days 1, 7, 28, 56, 63, 84, 168, and 336
Interferon-gamma-positive cells against spike protein from SARS-CoV-2 ancestral (Wuhan) strain, selected SARS-CoV-2 variants (Beta, Delta and Omicron), SARS-CoV-1 and MERS-CoV
Geometric mean number of interferon-gamma-positive cells per million peripheral blood mononuclear cells (PBMCs) by ELISPOT using spike protein from SARS-CoV-2 ancestral (Wuhan) strain, selected SARS-CoV-2 variants (Beta, Delta and Omicron), SARS-CoV-1 and MERS-CoV at Days 1, 7, 28, 56, 63, and 84
Time frame: Study days 1, 7, 28, 56, 63, and 84
Serum binding IgG subclasses
Serum binding IgG subclasses as a marker of Th1 (IgG1 and IgG3) and Th2 (IgG4) dominated responses at Days 1, 7, 28, 56, 63, and 84
Time frame: Days 1, 7, 28, 56, 63, and 84
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