Sample size justification
SAEs, viremia
VIREMIA
The sample size was chosen to power our primary safety (n = 45) and immunogenicity (n = 15 per group) endpoints. The primary safety endpoint is the frequency and severity of local and systemic reactogenicity signs and symptoms during the 28 day period after each vaccination, unexpected AEs up to 28 days after each vaccination, and SAEs through day 180 in any group (n = 45 total). The study will pause for a safety evaluation if one SAE or at least two similar ≥ grade 3 AEs that are possibly, probably, or definitely related to the vaccine are observed. Based on previous work with this vaccine candidate, we hypothesize that the true SAE probability is < 10%, and the probability of observing two similar grade 3 or 4 AEs is < 15%. If the true SAE rate is 10%, then there is a 90% probability that ≥ 1 SAE will be observed by the time 22 participants have been enrolled in the trial. Alternatively, if the true SAE rate is 0.2%, then there is a 10% probability of observing one SAE among 45 participants. If the true rate of ≥ 2 grade 3/4 AEs of similar types is 15%, then there is an 80% probability of observing this among the first 29 trial participants. However, if the true rate of 2 similar grade 3/4 AEs is 0.5%, then there is a 2.8% probability of observing this among the 45 participants.The primary immunologic comparisons in this study are to determine whether there is an increase in DENV neutralizing antibody GMT between days 0 and 28 within each group and to compare mean peak viremia titer among groups measured from days 3 to 15. With 15 participants in each group, there will be 90% power to detect a fold-increase in GMT of 5.36 (or log