Statistical considerations
SARS-COV-2 INFECTION
Total 372 participants were randomized in the study (186 in each prime cohort). Assuming non-evaluable participants ≤ 15% (158 evaluable participants for each cohort), group sample sizes of 93 each in each vaccine group would provide 80% power to detect non-inferiority using a one-sided, two-sample t-test, with a true ratio of the means of 1.00, one-sided significance level (alpha) of 0.025 and coefficients of variation of 1.1. Non-inferiority of SII-NVX-CoV2373 booster over the control vaccine for each cohort was to be concluded separately if the lower limit of the two-sided 95% confidence interval (CI) for the geometric mean ELISA units (GMEU) ratio for anti-S IgG and geometric mean titers (GMT) ratio for nAbs between SII-NVX-CoV2373 and the control vaccine at day 29 was > 0.67 (non-inferiority margin). The same sample size provided 82% power to demonstrate non-inferiority in terms of difference in proportion of participants with seroresponse (anti-S IgG and nAbs) between SII-NVX-CoV2373 and the control vaccine at day 29, using a one-sided, two-sample z-test at alpha level of 0.025. Proportion of participants achieving seroresponse for control arm was assumed 95% and the margin of non-inferiority was −10%. The true difference of the proportion was assumed to be 0. Sample size calculations were performed using a non-inferiority test for the ratio of two means in PASS 15.0.7 Version software.Analysis of Covariance (ANCOVA) was fitted to the log transformed anti-S IgG or nAbs for vaccine group, log baseline titer, age, sex, duration between first and second dose of primary immunization, duration between second dose to booster dose. Individual mean and 95% CI by treatment group from this model were used to estimate GMTs/GMEUs and geometric mean ratio (GMR) with 95% CI by back transforming to the original scale for non-inferiority comparison at day 29. The unadjusted GMTs/GMEUs were also summarized. The difference between the vaccine groups in the proportion of the participants with seroresponse along with two-sided 95% CIs were calculated using the Miettinen and Nurminen method.Enrolled Population was all participants who provided written informed consent, regardless of screening, randomization and treatment status in the study. Safety Population included all participants who received the study vaccines. Per Protocol population consisted of all participants who received the study vaccine, provided an evaluable serum sample post vaccination for at least one assessment, had baseline (day 1) immunogenicity data available, excluding any data from time points following a SARS-CoV-2 infection or major protocol deviation before day 29. This was the primary population for immunogenicity analyses. Full Analysis Population comprised of all participants who received the study vaccine and provided an evaluable serum sample post vaccination for at least one assessment.Continuous data was described using descriptive statistics (n, mean, standard deviation, median, minimum, and maximum). Categorical data was described using the participant count and percentage for each category.All statistical analyses were performed using SAS