This prospective, single-center, randomized, placebo-controlled, observer-blind Phase 1/2 study includes two separate parts. Part 1 is a first-in-human, Phase 1 study designed to evaluate the safety, tolerability and immunogenicity of the COVIVAC vaccine at three different dose levels (1, 3, and 10 µg) without adjuvant, and at one dose level (1 µg) with the adjuvant CpG 1018, in a total of 120 subjects aged 18-59 years. (Part 2 will be registered in a separate record)
This prospective, single-center, randomized, placebo-controlled, observer-blind Phase 1/2 study includes two separate parts. Part 1 is a first-in-human, Phase 1 study designed to evaluate the safety, tolerability and immunogenicity of the COVIVAC vaccine at three different dose levels (1, 3, and 10 µg) without adjuvant, and at one dose level (1 µg) with the adjuvant CpG 1018, in a total of 120 subjects aged 18-59 years. An interim analysis of Phase 1 data conducted after the last subject last visit for V6 (D57) will serve as the basis for decisions about down selection and advancing to Part 2 of the study (Phase 2). Down selection and advancement to Part 2 (Phase 2) will be based on the following parameters: * Post-dose 2 immunogenicity results at the aggregate treatment level o A threshold immune response at Visit 5 (D43) will be required: the observed seroresponse rate in a treatment group (defined as the percentage of subjects with at least a 4-fold rise from baseline in 80% neutralizing antibody titers) will need to be ≥52% at the LL of the 95% CI for that treatment (vaccine formulation) to be considered for advancement to Phase 2. * Post-dose 1 and post dose 2 safety results including all solicited and unsolicited adverse events, serious adverse events, and clinical laboratory results. The following process will be followed for the decision about down selection and advancing to Part 2 (Phase 2): * The DSMB will review the unblinded safety data and provide a recommendation to the Sponsor on whether the safety profile is acceptable for advancing a formulation to Phase 2. * The Sponsor will review the DSMB recommendation in conjunction with the immunogenicity data and select two formulations to advance to Phase 2. o If multiple formulations achieve the threshold immune response (as well as have an adequate safety and tolerability profile per the DSMB), the Sponsor will select two formulations to advance to Phase 2 based on consideration of such factors as the relative functional immunogenicity of these formulations, opportunity for dose sparing, and opportunity to limit cost and possible supply constraints associated with use of the CpG adjuvant. * The selection and recommendation to advance to Phase 2 along with the interim report will be jointly reviewed by NIHE's IRB and MoH prior to Phase 2 enrollment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
120
COVIVAC vaccine, manufactured by IVAC with or without adjuvant CpG1018 for prevention of COVID-19
Phosphate buffer solution (pH 7.2), manufactured by IVAC
Hanoi Medical University
Hanoi, Vietnam
Solicited Adverse Events
Percentage of participants with solicited local and systemic adverse events (AEs)
Time frame: During the first 7 days after each vaccination
Clinical Safety Tests
Percentage of participants with clinically significant hematological and biochemical abnormalities
Time frame: At 7 days post each vaccination
Unsolicited Adverse Events
Number of participants with any unsolicited adverse event
Time frame: During the first 28 days after each vaccination
Serious Adverse Event
Number of participants with serious adverse events (SAEs)
Time frame: Throughout the Study Period (until Day 197)
Medical Attended Adverse Events
Number of participants with medically-attended AEs (MAAEs)
Time frame: Throughout the Study Period (until Day 197)
Adverse Event of Special Interest
Number of participants with adverse events of special interest (AESI) , including AESI relevant to COVID-19, and potential immune-mediated medical conditions (PIMMC)
Time frame: Throughout the Study Period (until Day 197)
GMT of 50% Neutralizing Antibody (NT50)
50% neutralizing antibody (NT50) geometric mean titer (GMT) against SARS-CoV-2 pseudovirus
Time frame: GMT of NT50 at 28 days after first vaccination, at 14 days and 6 months after the second vaccination
Geometric Mean Fold Rise (GMFR)
Geometric mean fold rise (GMFR) (from baseline) in NT50 against SARS-CoV-2 pseudovirus
Time frame: GMFR at 28 days after first vaccination, at 14 days and 6 months after the second vaccination
Seroresponse in NT50
Percentage of subjects with NT50 seroresponse against SARS-CoV-2 pseudovirus as defined by (1) a ≥ 4-fold increase from baseline, and (2) a ≥ 10-fold increase from baseline
Time frame: Seroresponse at 28 days after first vaccination, at 14 days and 6 months after the second vaccination
Anti-S IgG GMC
Immunogenicity outcome measurement
Time frame: GMC of Anti-S IgG at 28 days after the first vaccination, at 14 days and 6 months after the second vaccination
GMFR in Anti-S IgG GMC
GMFR (from baseline) in anti-S IgG GMC
Time frame: GMFR at 28 days after the first vaccination, 14 days and 6 months after the second vaccination
Seroresponse in Anti-S IgG Concentration
Percentage of subjects with seroresponses in anti-S IgG titer as defined by (1) a ≥ 4-fold increase from baseline, and (2) a ≥ 10-fold increase from baseline
Time frame: Seroresponse at 28 days after the first vaccination, 14 days and 6 months after the second vaccination
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