Study of a Candidate Clostridium Difficile Toxoid Vaccine in Subjects at Risk for C. Difficile Infection

The study was designed as an event-driven group sequential protocol with 4 interim analyses at defined information milestones and a final analysis when a specific number of clinical endpoints are reached. Analyses of trial futility (non-efficacy) were to be performed at the first 2 interim analyses, and the study was to be stopped if either of those analyses provided robust and compelling evidence that meaningful levels of vaccine efficacy (VE) would not be demonstrated. Following completion of the first interim analysis (50 cases of confirmed CDI observed), the futility criterion was met and in accordance with IDMC recommendation, enrollment and further vaccination ceased in November 2017. Due to the early termination of the study, some of the planned secondary efficacy endpoints could not be analyzed as all planned data were not collected. Participants were randomized to receive either the candidate vaccine or a placebo that was to be administered in a 3-dose schedule. At the time of group assignment, 928 participants (10% of total enrollment) were randomized to an immunogenicity subset; and 1859 participants (20% of total enrollment) were randomized to a reactogenicity subset. Safety was assessed in all participants in terms of unsolicited adverse events from Day 0 to Day 60, as well as serious adverse events (SAEs) throughout the study. Solicited adverse reactions were collected for 6 days following each injection in the reactogenicity subset.