Evaluation of fecal microbiota, live (RBL) for the prevention of recurrent Clostridioides difficile infection: Canadian subgroup analysis of an open-label phase 3 study

Abstract Background Fecal microbiota, live (RBL) is a single-dose, broad consortium, microbiota-based product approved in the United States and Canada for preventing recurrent Clostridioides difficile (C. diff) infection in adults following standard-of-care (SOC) treatment. Methods PUNCH CD3-OLS was a phase 3, open-label, multicenter study evaluating safety and effectiveness of RBL in adults, including those with comorbidities, with recurrent C. diff infection. Participants were aged ≥18 years, had recurrent C. diff infection (≥1 recurrence/≥2 severe episodes; diagnostic method was site-specific), and received SOC antibiotics before rectal administration of RBL. The primary endpoint was treatment-emergent adverse events (TEAEs) through 6 months post-administration. Secondary endpoints included treatment success at 8 weeks and sustained clinical response at 6 months. This subgroup analysis examined outcomes among Canadian participants across 5 sites. Results Among 117 Canadian participants who received RBL, most were female and White, with a mean age of 61.3 years; 24.8% reported a first recurrence. The enrolling C. diff infection was diagnosed via polymerase chain reaction for 70.9% of participants. TEAEs, reported in 59.8% of participants, were mostly mild-to-moderate gastrointestinal events. Serious TEAEs occurred in 5.1% of participants within 8 weeks and 6.8% between 8 weeks and 6 months. Treatment success was achieved by 75.2% of participants at 8 weeks, among whom 90.9% maintained a sustained clinical response at 6 months. Conclusions Safety and effectiveness outcomes in Canadian participants were consistent with those observed in the PUNCH CD3 randomized controlled trial population, supporting the use of RBL for prevention of recurrent C. diff infection in Canada. ClinicalTrials.gov identifier NCT03931941.