CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection

Donskey,Curtis J.; Dubberke,Erik R.; Klein,Nicola P.; Liles,Elizabeth G.; Szymkowiak,Katarzyna; Wilcox,Mark H.; Lawrence,Jody; Bouguermouh,Salim; Zhang,Haiying; Koury,Kenneth; Bailey,Ruth; Smith,Helen M.; Lockhart,Stephen; Lamberth,Erik; Kalina,Warren V.; Pride,Michael W.; Webber,Chris; Anderson,Annaliesa S.; Jansen,Kathrin U.; Gruber,William C.

CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection

All Authors

Donskey,Curtis J.

Dubberke,Erik R.

Klein,Nicola P.

Liles,Elizabeth G.

Szymkowiak,Katarzyna

Wilcox,Mark H.

Lawrence,Jody

Bouguermouh,Salim

Zhang,Haiying

Koury,Kenneth

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LTHT Author

Wilcox, Mark

LTHT Department

Pathology
Microbiology

Publication Date

2024

Item Type

Article

Abstract

Background Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention. Methods This phase 3 observer-blinded study randomized (1:1) ?50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (?3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ?14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability and safety were assessed. Results The primary end point was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ?14 days PD3 vaccine efficacy (VE) = 31.0% (96.4% confidence interval CI], ?38.7% to 66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ?14 days PD2 VE = 28.6% (96.4% CI, ?28.4% to 61.0%)]. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P =.02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE = 100%; 95% CI, 59.6% to 100.0%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE = 100%; 95% CI, 54.8% to 100.0%). Local reactions were more frequent in PF-06425090 recipients, and systemic events were generally similar between groups; most were mild to moderate. Adverse event rates were similar between groups. Conclusions Three PF-06425090 doses were safe and well tolerated. Although the primary end point was not met, PF-06425090 reduced symptom duration, CDI that required medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden. Clinical Trials Registration NCT03090191.