Thomas Louie, MD

Credit: University of Calgary

Early phase data points to success for VE303, a potential treatment that helps prevent recurrent clostridiodes difficile infections (CDI) for patients who are at an elevated risk of recurrence.

A team, led by Thomas Louie, MD, University of Calgary and Foothills Medical Centre, determined the efficacy of VE303 in adults at a higher risk of recurrent CDI.

The Need for Alternatives

In recent years, the use of fecal microbiota transplantation (FMT) has yielded successful results in this patient population. However, there remains a need for other treatment options.

“There are logistical and safety concerns associated with fecal microbiota transplants and other donor derived products, such as donor variability and quality and the risk of transmission of pathogenic and/or antibiotic-resistant microbes,” the authors wrote. “Alternatives to donor-derived products are needed, such as defined biotherapeutic interventions of standardized composition, to restore the microbiome and safely prevent future CDI recurrences.”

VE303 is a defined bacterial consortium of 8 strains of commensal Clostridia

The investigators sought a primary objective of the recommended dosing of VE303 for a potential phase 3 trial.

The Trial

In the phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, the investigators examined 79 patients at 27 US and Canadian sites between February 2019 and September 2021. The median age of the patient population was 63.5 years and 70.5% of the participants were female.

Each participant was aged 18 years or older with laboratory-confirmed CDI with 1 more prior episodes of CDI in the previous 6 months, as well as patients with primary CDI at a high risk for recurrence, defined at those aged 75 years or older or those aged 65 years or older with at least 1 risk factor such as creatinine clearance <60 mL/min/1.73m², proton pump inhibitor use, or remote [>6 months earlier] CDI history.

Each participant was treated with either high-dose VE303 (8.0 Å~ 109 colony-forming units [CFUs]) (n = 30), low-dose VE303 (1.6 Å~ 109 CFUs) (n = 27), or placebocapsules (n = 22) orally once daily for 14 days.

The investigators sought primary efficacy endpoints of the proportion of participants with recurrent CDI at week 8 using a combined clinical and laboratory definition.

This was analyzed in 3 prespecified analyses, using successively broader definitions for an on-study CDI recurrence, including diarrhea consistent with CDI combined with a toxin-positive stool sample, diarrhea consistent with CDI combined with a toxin-positive, polymerase chain reaction-positive, or toxigenic culture-positive stool sample and diarrhea consistent with CDI plus laboratory confirmation or treatment with a CDI-targeted antibiotic in the absence of a stool sample.

The baseline characteristics were similar across the 3 groups--high-dose VE303 (n = 29; 1 additional participant excluded from efficacy analysis), low-dose VE303 (n = 27), and placebo (n = 22) groups.

The rate of CDI recurrence through week 9 using the efficacy analysis 3 definition was 13.8% (n = 4) for the high-dose VE303 group, compared to 37% (n = 10) for the low-dose VE303 group and 45.5%(n = 10) for the placebo group (P = .006, high-dose VE303 vs placebo).

“Among adults with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence, high-dose VE303 prevented recurrent CDI compared with placebo,” the authors wrote. “A larger, phase 3 study is needed to confirm these findings.”