In phase II, a total of 300 eligible subjects will be randomly allocated in a 1:1 ratio to receive PIKA COVID-19 vaccine or the comparator inactivated COVID-19 vaccine. The ratio of the GMT of neutralizing antibody on Day 14 after the booster dose of PIKA COVID-19 vaccine group and inactivated COVID-19 vaccine group will be calculated. Based on the Phase I immunogenicity data of PIKA vaccine, the proposed Phase II sample size results in nearly 100% power in a two-sample t test of the log- transformed neutralizing antibody titers with a two-sided alpha=0.05. Among 300 subjects, at least 200 subjects will be enrolled as subset of long term immunogenicity and 100 subjects will be enrolled as subset of early immunogenicity. Among the 100 early immunogenicity subset, the ratio of the GMT of neutralizing antibody on Day 7 after the booster dose of PIKA COVID-19 vaccine group and inactivated COVID-19 vaccine group will be calculated. Therefore, the 100 subjects randomized to the early immunogenicity subset will have additional blood sampling on Day 7. After completion of the 7-day safety observation following the immunization of all subjects in the Phase II trial, a Safety Monitoring Committee (SMC) meeting will be held to determine whether to initiate enrollment of participants in the Phase III trial. In phase III, total 9,000 eligible subjects will be randomly allocated in a 1:1 ratio to the PIKA COVID-19 vaccine group or the comparator inactivated COVID-19 vaccine group. The sample size provides an approximately 90% power to detect a protection rate of at least 65% by PIKA vaccine in a Poisson regression analysis with a one-sided alpha of 0.025. The calculations consider an interim analysis performed with 50% of the information collected using a Pocock boundary to adjust for multiplicity. A 1% infection rate in the control group and an approximately a 10% attrition rate are assumed. It is of note that while the actual background incidence rate can vary, the sample size requirement amounts to achieving an observation of 82 COVID-19 cases to ensure the statistical power under the 65% protection rate assumption. Similarly, the interim analysis will need to be conducted at when approximately 41 cases are observed to maintain the planned operating characteristics. Among total subjects, at least 6% subjects will be enrolled as subset of immunogenicity. Eligible subjects will receive a dose of investigational vaccine via intramuscular injection in deltoid muscle on Day 0. All subjects will be monitored for at least 30 minutes after injection. Solicited AEs will be recorded for 7 days. Unsolicited AEs and MAAEs will be recorded for 28 days following injection. SAEs, SUSARs, AESIs will be recorded for the entire duration of the study. It will take about 13 months for each subject from enrollment to the last visit. Some subjects may withdraw or discontinue from the study during the study for any reason.
This is a Phase II/III, randomized, double-blinded study in adults ≥ 18 years old who received 2 or more doses of inactivated COVID-19 vaccine to evaluate the efficacy, safety and immunogenicity of a booster dose of PIKA COVID-19 vaccine compared to the comparator inactivated COVID-19 vaccine. Phase II/III will be a competitive enrollment process in all participating countries. Once the target number of subjects is reached, the enrollment in all participating countries in the particular phase will be stopped.