This study is a phase I /II adaptive clinical trial to evaluate the safety, tolerability and the Immunogenicity of Ad5-nCoV in healthy adults from 18 to \<55 and 65 to \<85 years of age,with the randomized, observer-blind, dose-escalation design
A total of 96 healthy adult volunteers will be vaccinated in phase I stepwised according to the dose-escalation design from the younger adults(18 to \<55) to the older adults(65 to \<85). There are 2 dosage level used in this phase: 5E10vp and 10E10vp, and 2 dose schedules: single dose and 2 dose. According to the pre-defined adaptive design standards, the trial will moved from Phase I to Phase II. In the phase II portion, A total of 600 healthy adult volunteers will be vaccinated according to the dose-escalation design from the younger adults(18 to \<55) to the older adults(55 to \<85). There are 2 dosage levels and schedules used in this phase,and will determine a final dose and schedule by the end. Some cohorts in the phase II trial will be included in the subsequent phase III trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
696
Intramuscular administration
Intramuscular administration
Canadian Center for Vaccinology
Halifax, Canada
Incidence of the Solicited AE in all groups
The occurrence of Solicited AE in all groups within 0-6 days after each vaccination;
Time frame: 0-6 days after each vaccination
Incidence of Unsolicited AE in all groups
The occurrence of Unsolicited AE in all groups within 0-28 days after each vaccination.
Time frame: 0-28 days after each vaccination
Incidence of Serious adverse events (SAE) in all groups
The occurrence of Serious adverse events (SAE) in all groups within 6 months after the final vaccination.
Time frame: 6 months after the final vaccination
Geometric mean titer (GMT) of the IgG antibody against SARS-CoV-2 (ELISA method);
Geometric mean titer (GMT) of the IgG antibody against SARS-CoV-2 measured on Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method);
Time frame: Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group
Seroconversion rate of the IgG antibody against SARS-CoV-2(ELISA method )
Seroconversion rate (%of subjects with 4-fold or greater increase in antibody level) of the IgG antibody against SARS-CoV-2 measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method );
Time frame: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group
Geometric Mean Increase Ratio (GMI) of the specific antibody against SARS-CoV-2(ELISA method);
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Geometric Mean Increase Ratio (GMI) of the specific antibody against SARS-CoV-2 measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method);
Time frame: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group
Geometric mean titer (GMT) of the neutralizing antibody against SARS-CoV-2(Pseudo-viral neutralization assay)
Geometric mean titer (GMT) of the neutralizing antibody against SARS-CoV-2 measured on Day 0, Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group (Pseudo-viral neutralization assay)
Time frame: Day 0, Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group
Seroconversion rate of the neutralizing antibody against SARS-CoV-2(Pseudo-viral neutralization assay)
Seroconversion rate of the neutralizing antibody against SARS-CoV-2 measured on Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group(Pseudo-viral neutralization assay);
Time frame: Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group
Geometric mean increase ratio (GMI) of neutralizing antibody against SARS-CoV-2 (Pseudo-viral neutralization assay)
Geometric mean increase ratio (GMI) of neutralizing antibody against SARS-CoV-2 measured on Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (Pseudo-viral neutralization assay)
Time frame: Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group
Geometric Mean Titer (GMT) of the neutralizing antibody against adenovirus type 5 vector
Geometric Mean Titer (GMT) of the neutralizing antibody against adenovirus type 5 vector measured on Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group;
Time frame: Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group
Geometric mean increase ratio (GMI) of the neutralizing antibody against adenovirus type 5 vector
Geometric mean increase ratio (GMI) of the neutralizing antibody against adenovirus type 5 vector measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group
Time frame: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group
cellular immune response by ELISpot
The positive rate of IFN-γ stimulated by S protein overlapping peptide library detected by ELISpot
Time frame: on Day 0, Day 14, Day 28 and Day 168 in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group
cellular immune response by ICS
The positive rate of IFN-γ, TNF-α, and IL-2 expressed by CD4+ and CD8+ T lymphocytes stimulated by S protein overlapping peptide library detected by Intracellular Cytokine Staining (ICS);
Time frame: Day 0, Day 14, Day 28 and Day 168 in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group