Safety and Efficacy of Fecal Microbiota, Live-jslm for Prevention of Recurrent Clostridioides difficile Infection Among Hospitalized Participants in PUNCH CD3-OLS

INTRODUCTION: Fecal microbiota, live-jslm (RBL) is the first single-dose, microbiota-based product approved by the US Food and Drug Administration and Health Canada to prevent recurrent Clostridioides difficile infection (rCDI) following standard-of-care antibiotics. The phase 3 PUNCH CD3-OLS study enrolled participants with numerous comorbidities and permitted inclusion of participants hospitalized due to rCDI. The safety and efficacy of RBL were evaluated in this subgroup analysis of hospitalized participants from PUNCH CD3-OLS. METHODS: The hospitalization subgroup included participants hospitalized for rCDI within 90 days prior to RBL administration. Participants received a single dose of RBL 24-72 h after completion of standard-of-care antibiotic treatment for rCDI. These exploratory analyses evaluated the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs), treatment success at 8 weeks, sustained clinical response at 6 months, and incidence of rehospitalization for rCDI during study participation. RESULTS: The hospitalization subgroup included 74 of 697 (10.6%) participants. Within 6 months following RBL administration, 47 (63.5%) and 350 (56.7%) participants in the hospitalization and nonhospitalization subgroups experienced TEAEs, respectively; most TEAEs were of mild to moderate severity. Serious TEAEs in the hospitalization subgroup were frequently related to preexisting conditions; none were related to RBL or its administration. Most participants (87.8% [65/74]) in the hospitalization subgroup were not rehospitalized within 6 months. Treatment success at 8 weeks was 62.5% (45/72) and 75.1% (449/598) among participants in the hospitalization and nonhospitalization subgroups, respectively. Of those achieving treatment success, 86.7% (39/45) and 91.3% (410/449) had sustained clinical response through 6 months in the hospitalization and nonhospitalization subgroups, respectively. CONCLUSION: RBL was safe and effective in a subgroup of hospitalized participants in the PUNCH CD3-OLS study. Efficacy in this subgroup was slightly lower than in nonhospitalized participants, but rCDI-related rehospitalization remained rare. TRIAL REGISTRATION: NCT03931941.