CLOVER: 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.
| Autor: | Donskey CJ; Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA., Dubberke ER; Division of Infectious Diseases, Washington University in St Louis, St Louis, MO, USA., Klein NP; Kaiser Permanente Vaccine Study Center, Oakland, CA, USA., Liles EG; Kaiser Permanente Center for Health Research, Portland, OR, USA., Szymkowiak K; Clinical Research, Synexus Polska Sp. z.o.o., Wroclaw, Poland., Wilcox MH; Leeds Teaching Hospitals NHS Trust and Leeds Institute of Medical Research, University of Leeds, Leeds, UK., Lawrence J; Pfizer Inc, Collegeville, PA, USA., Bouguermouh S; Pfizer Inc, Pearl River, NY, USA., Zhang H; Pfizer Inc, Collegeville, PA, USA., Koury K; Pfizer Inc, Pearl River, NY, USA., Bailey R; Pfizer Ltd, Hurley, UK., Smith HM; Pfizer Ltd, Hurley, UK., Lockhart S; Pfizer Ltd, Hurley, UK., Lamberth E; Pfizer Inc, Collegeville, PA, USA., Kalina WV; Pfizer Inc, Pearl River, NY, USA., Pride MW; Pfizer Inc, Pearl River, NY, USA., Webber C; Pfizer Ltd, Hurley, UK., Anderson AS; Pfizer Inc, Pearl River, NY, USA., Jansen KU; Pfizer Inc, Pearl River, NY, USA., Gruber WC; Pfizer Inc, Pearl River, NY, USA., Kitchin N; Pfizer Ltd, Hurley, UK. |
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| Jazyk: | angličtina |
| Zdroj: | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2024 Aug 24. Date of Electronic Publication: 2024 Aug 24. |
| DOI: | 10.1093/cid/ciae410 |
| Abstrakt: | 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 (0,1,6-months). Primary endpoints 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 endpoints), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability/safety was assessed. Results: The primary endpoint was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE)=31.0% (96.4%CI: -38.7%-66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE=28.6% (-28.4%-61.0%)]). Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P=0.02). 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%-100.0%]) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE=100% [54.8%-100.0%]). Local reactions were more frequent in PF-06425090 recipients and systemic events were generally similar between groups; most were mild-to-moderate. AE rates were similar between groups. Conclusions: Three PF-06425090 doses were safe and well-tolerated. Although the primary endpoint was not met, PF-06425090 reduced symptom duration, CDI requiring medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden. NCT03090191. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.) |
| Databáze: | MEDLINE |
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