A phase 3 clinical trial evaluating Pfizer's vaccine candidate, PF-06425090, for Clostridioides difficile infection (CDI) did not meet its primary endpoint of reducing the incidence of CDI in at-risk adults aged 50 and older. The global CLOVER trial, conducted across 23 countries from March 2017 to December 2021, assessed the efficacy of the genetically detoxified toxin vaccine in a cohort of 17,535 participants.
Trial Details and Results
The randomized, placebo-controlled trial involved participants receiving three doses of either PF-06425090 or a placebo. The primary endpoints were defined as the first CDI episode occurring 14 or more days post-dose three (PD3) and post-dose two (PD2). While the vaccine demonstrated a vaccine efficacy (VE) of 31% post-dose three and 28.6% post-dose two, the 96.4% confidence intervals ranged well below 0, indicating a lack of statistically significant reduction in CDI incidence.
Specifically, among participants who received all three doses, 17 in the PF-06425090 group and 25 in the placebo group experienced a primary CDI episode 14 or more days post-dose three. For those who received two doses, 24 vaccine recipients and 34 placebo recipients had a first CDI episode 14 or more days post-dose two.
Secondary Outcomes and Safety
Despite not meeting the primary endpoint, the trial revealed potential benefits in secondary outcomes. The median CDI duration was notably shorter in the PF-06425090 group (1 day) compared to the placebo group (4 days). Furthermore, a post-hoc analysis indicated that none of the vaccine recipients with a first CDI episode required CDI-related medical attention, compared to 11 in the placebo group, suggesting a VE of 100%. Similarly, no vaccine recipients required antibiotic treatment, while 10 placebo recipients did, also indicating a VE of 100%.
The vaccine was found to be safe and well-tolerated. Local reactions were more frequent in the PF-06425090 group, but systemic events, predominantly mild to moderate, were similar across both groups. Adverse event rates were also comparable.
Implications and Future Directions
Trial investigators suggest that despite the failure to meet the primary endpoint, PF-06425090 could still offer a public health benefit by reducing the overall disease burden of CDI. "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," the investigators wrote. They also noted that limiting the need for medical attention could alleviate healthcare resource strains and reduce potential antibiotic exposure, which may help mitigate the increasing global threat of antimicrobial resistance.
