CRS3123 Phase 2 Trial in Primary or First Recurrent C. Difficile

Key Takeaways

• Test-of-cure efficacy was similar across the two CRS3123 groups and the vancomycin group.
• Recurrence through day 40 occurred in 0 of 13 patients with CRS3123 200 mg, 1 of 14 with CRS3123 400 mg, and 3 of 13 with vancomycin.
• Treatment-emergent adverse events were generally mild to moderate, and the only serious adverse event was pneumonia in the vancomycin group, considered unrelated to study drug.

In a phase 2 multicenter trial, adults with a primary episode or first recurrence of Clostridioides difficile infection had similar test-of-cure results across treatment groups, including 100% clinical cure in the CRS3123 400 mg group. The randomized, double-blind, vancomycin-controlled study compared two oral CRS3123 regimens with oral vancomycin over 10 days. Recurrence was tracked through day 70, and safety findings were reported across all assigned groups.

The trial ran at 14 sites in the USA and Canada and evaluated CRS3123, a protein-synthesis inhibitor active in bacteria expressing type 1 methionyl-tRNA ligase. Participants were randomized 1:1:1 to CRS3123 200 mg twice daily, CRS3123 400 mg twice daily, or vancomycin 125 mg four times daily for 10 days. Adults were eligible if they had at least three unformed bowel movements within 24 hours before randomization, stool toxin A or B detection, and no more extensive recent recurrence history. Among 58 screened individuals, 43 were randomized; mean age was 58.4 years, 77% were women, 31 had a primary episode, and 12 had a first recurrence. The primary efficacy endpoint was clinical cure at the test-of-cure visit on days 12 to 15, and recurrence was assessed on days 40 and 70 in the microbiological intention-to-treat population.

Clinical cure at test of cure was 13 of 14 patients, or 93%, with CRS3123 200 mg and 15 of 15, or 100%, with CRS3123 400 mg. Vancomycin produced clinical cure in 13 of 14 patients, or 93%. No patient had clinical failure at test of cure, and two responses were indeterminate because of missing data, one in CRS3123 200 mg and one in vancomycin. In the microbiological intention-to-treat population, recurrence through day 40 was lower in the CRS3123 groups, with one additional recurrence by day 70 in the higher-dose group. Short-term cure rates were similar, with fewer observed early recurrences in the CRS3123 groups.

All randomized patients received at least one dose of the assigned drug, and treatment-emergent adverse events were similar across groups and generally mild to moderate in severity. Adverse events considered possibly related to study drug occurred in one patient with CRS3123 200 mg, three with CRS3123 400 mg, and none with vancomycin. These possibly related events were all grade 1 or 2. The only serious adverse event was pneumonia in the vancomycin group, and investigators considered it unrelated to study drug. The authors described both CRS3123 doses as safe and well tolerated, with efficacy similar to vancomycin at test of cure and lower observed recurrence, findings they said supported further development.