Oral microbes effective for prevention of recurrent Clostridium difficile infections

An investigational oral microbiome therapeutic successfully prevented the recurrence of Clostridium difficile infections in the largest open-label study ever performed with an oral microbiome preparation. Moreover, a substantial treatment effect can still be expected with a second dose.

Currently, disruption of the microbiome is considered essential to the pathogenesis of recurrent Clostridium difficile infections (CDI). However, few trials have evaluated the efficacy and safety of orally administered microbiome therapeutics. Prof. Jessica Allegretti (Brigham and Women’s Hospital, MA, USA) presented the results of the PRISM-EXT (NCT03497806) trial, where the safety and efficacy of open-label treatment with CP101 in adults with recurrent CDI was evaluated [1]. CP101 is an investigational, orally-administered, microbiome therapeutic designed to restore microbiome diversity and enable early intervention in recurrent CDI.

PRISM-EXT is the largest open-label study of an investigational oral microbiome therapeutic. As Prof. Allegretti pointed out in her presentation, the 132 participants either rolled over from PRISM3 after experiencing a CDI recurrence (n=50) or directly enrolled after experiencing a CDI recurrence without previously participating in PRISM3 (n=82). The CDI episode was diagnosed prior to trial entry by PCR-based or toxin EIA-based testing in line with current guidelines. All participants received a one-time oral administration of CP101 without bowel preparation following standard-of-care (SOC) antibiotics. The primary efficacy endpoint was sustained clinical cure, defined as an absence of CDI recurrence through week 8 following dosing.

80.3% of participants had no CDI recurrence through week 8 following administration of SOC antibiotics and CP101 in PRISM-EXT. Efficacy was maintained with a sustained clinical cure rate of 78.8% through week 24. Of the 20 participants who had a recurrence in PRISM3 and received a 2^nd CP101 dose in PRISM-EXT, 70% had no CDI recurrence through week 8 after the 2^nd dose.

Microbiome diversity increased following administration of the oral microbiome therapeutic in all participants. Moreover, the results suggest that a significant proportion of patients that shows no response to a first dose of CP101 can be successfully treated with a second dose of the preparation. CP101 was well-tolerated with no treatment-related serious adverse events.

1. Allegretti JR, et al. CP101, an investigational orally administered microbiome therapeutic, was effective for prevention of recurrent C. difficile infection: Results from open-label prims-ext trial. Lecture Tu1519, Digestive Disease Week 2022, 21‒24 May, San Diego, CA, USA.

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Posted on 14 June 202227 March 2024