Crestone, Inc. announced positive topline results from its Phase 2 clinical trial evaluating CRS3123 for the treatment of Clostridioides difficile infection (CDI). The study demonstrated that CRS3123 achieved comparable clinical cure rates to vancomycin, the current standard of care, while significantly reducing recurrence rates. The findings suggest that CRS3123 could offer a valuable new approach to managing this challenging infection.
The Phase 2 trial was a randomized, double-blind, comparator-controlled, multicenter study involving 43 adults diagnosed with a primary episode or first recurrence of CDI. Participants were administered either one of two dosages of CRS3123 (200 mg and 400 mg twice daily) or vancomycin (125 mg four times daily) for 10 days. The primary endpoint was the rate of clinical cure at day 12 in the intent-to-treat (ITT) population.
Key Findings
The clinical cure rates at day 12 were 97% (28/29) in patients receiving CRS3123 and 93% (13/14) in those receiving vancomycin. Notably, the recurrence rates at day 40 were considerably lower in the CRS3123 group (4%) compared to the vancomycin group (23%). CRS3123 was also well-tolerated, with no serious treatment-emergent adverse events reported.
"Treatment of C. difficile infection remains in urgent need of agents that spare normal gut microbes, so they can reconstitute the microbiome and prevent further recurrences of CDI," said Dr. Thomas Louie of the University of Calgary, Canada, the principal investigator for the study. "The findings of this study support CRS3123 as such a candidate for further development."
CRS3123: A Narrow-Spectrum Approach
CRS3123 is a small molecule that selectively inhibits bacterial methionyl-tRNA synthetase, an enzyme not present in human cells or other important gut bacteria. This narrow-spectrum activity allows CRS3123 to target C. difficile while minimizing disruption to the normal gut microbiota. In addition to blocking C. difficile growth, CRS3123 also inhibits toxin production and spore formation.
Implications for CDI Treatment
CDI is a significant healthcare burden, with almost half a million infections and approximately 30,000 deaths occurring annually in the U.S. Current treatments often involve broad-spectrum antibiotics, which can disrupt the gut microbiome and lead to high recurrence rates (20-40%). A therapy that effectively treats CDI while preserving the gut microbiota is urgently needed.
"It is now abundantly clear that curbing C. difficile while preserving healthy intestinal flora is what we want in a CDI therapeutic," stated Dr. Mark Wilcox, Professor at Leeds Teaching Hospitals and University of Leeds. "The outcome of this phase 2 study further reinforces that goal."
Future Directions
Based on these promising results, the National Institute of Allergy and Infectious Diseases (NIAID) has exercised its option to provide Crestone with $4.5 million in new funding for microbiome analyses, manufacturing process optimization, and other Phase 2 supporting studies. Crestone plans to present the full results from the Phase 2 trial at an upcoming medical conference and is seeking discussions with the FDA and potential development partners to advance CRS3123 into pivotal studies.
