Jennifer Oosthuizen / CDC
A Clostridioides difficile vaccine candidate was safe, well tolerated, and reduced C difficile infection (CDI) severity but did not reduce incidence of CDI in at-risk adults, according to the results of a phase 3 randomized clinical trial published late last week in Clinical Infectious Diseases.
The global, phase 3 CLOVER trial, conducted in 23 countries from March 2017 through December 2021, assessed the efficacy of PF-06425090, a genetically detoxified toxin C difficile vaccine candidate from Pfizer, in adults 50 and older who were considered at increased CDI risk. Overall, 17,535 participants (mean age, 68; 51.5% female; 79.2% White) were randomized to receive three doses of PF-06425090 or placebo. The primary end points were the first CDI episode 14 or more days post–dose three (PD3) and post–dose two (PD2). CDI duration, need for CDI-related medical attention, and antibiotic use PD3 were also evaluated.
Among the participants who received all three doses, 17 PF-06425090 and 25 placebo recipients had a primary CDI episode 14 or more days PD3, resulting in vaccine efficacy (VE) of 31%, but the 96.4% confidence interval ranged well below 0. Among those who received two doses, 24 PF-06425090 and 34 placebo recipients had a first CDI episode 14 or more days PD2, for a VE of 28.6%, with a similarly wide confidence interval. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days). Of participants with a first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post-hoc analysis estimated VE, 100%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE, 100%).
Local reactions were more frequent in PF-06425090 recipients, while systemic events, most of which were mild-to-moderate, were generally similar between groups. Adverse event rates were similar between groups.
Potential public health benefit
The trial investigators say that while the primary end point wasn’t met, the results suggest PF-06425090 could provide a public health benefit.
“Together, these findings suggest PF-06425090 may reduce overall disease burden by potentially reducing CDI severity in vaccine recipients and consequent need for medical interventions,” trial investigators wrote. “Limiting need for medical attention not only alleviates healthcare resource strains but reduces potential for antibiotic exposure, which may help mitigate increasing global threats of antimicrobial resistance.”
