Statistical analysis
ADVERSE EVENTS, DISEASE
In accordance with the 2020 WHO guidelines,The originally planned interim analysis was scheduled to be done when the number of individuals for the primary efficacy endpoint reached 75 (The safety data were collected for 12 months after the final dose (ie, safety observation period; completed on June 30, 2023), whereas the efficacy analysis was case driven and the observation period for efficacy endpoints (ie, the primary efficacy analysis was triggered once the number of cases for the primary endpoint reached 150; The safety analysis population comprised all participants who had received at least one dose of dNS1-RBD or placebo, and it was based on the actual administrations, correcting for vaccination errors. The primary efficacy analysis included the per-protocol population. Additional prespecified efficacy analyses were performed in the modified intention-to-treat population (ie, all randomly assigned patients who received two doses and were followed up for 15 days or longer after the second dose; listed in the protocol as mITT2).The rate difference, defined as the difference in incidence of adverse events or reactions between the vaccine group and the placebo group, was used in the safety analysis to compare the safety profile of the vaccine and placebo. For each rate difference, we estimated the 95% CIs using the Wilson score method. We also did prespecified subgroup analyses of the safety endpoints by age group (18–59 years We also did analyses to assess vaccine efficacy in the short term (15–90 days; prespecified) and estimate the incidence of hospitalisation among participants who received at least one dose (post hoc). To further differentiate the severity of COVID-19 in non-hospitalised individuals or those with mild disease, we quantified disease severity according to the number of suspected symptoms in a post-hoc analysis, which was defined as omicron symptom index (Independent statisticians from the contract research organisation (Hangzhou Tigermed Consulting) did all the analyses using SAS (version 9.4). An independent data monitoring committee was responsible for safeguarding trial participants, assessing safety during the trial period, and reviewing data after the final analysis. A blinded independent endpoint adjudication committee confirmed the endpoints and determined the severity of COVID-19 on the basis of clinical manifestation and related data. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2100051391).