Background: Microbiota-based treatments have shown promise to reduce recurrence for recurrent Clostridioides difficile infections (rCDI), but consistent and reliable safety data are needed to support regulatory approvals and broaden patient access. Here we provide cumulative safety data from 5 prospective clinical studies evaluating RBX2660—a standardized, microbiota-based investigational live biotherapeutic—for reducing rCDI.

Methods: This analysis included 3 phase 2 (PUNCH CD, PUNCH CD2, PUNCH CD Open Label) and 2 phase 3 trials (PUNCH CD3, PUNCH CD3-OLS ad hoc analysis). Participants were ≥18 years of age with documented rCDI who completed standard-of-care antibiotic therapy prior to treatment with RBX2660. PUNCH CD3-OLS allowed participants with comorbidities of irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). Depending on the trial, assigned study treatment was 1 or 2 doses of RBX2660 (or placebo), administered rectally. Participants whose CDI recurred within 8 weeks were eligible for additional RBX2660 treatment. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; CD2 and CD Open Label recorded TEAEs for 24 months.

Results: Among 749 participants who received at least 1 RBX2660 dose (assigned treatment or after recurrence), 429 (57.3%) received 1 dose, 294 (39.3%) received 2 doses, 14 (2.3%) received 3 doses, and 12 (1.9%) received 4 doses. Eighty-three participants received placebo only. A total of 2319 TEAEs were reported from 521 RBX2660-treated participants (69.6%), compared to 174 TEAEs in 50 placebo-only treated participants (60.2%). Most TEAEs were mild or moderate in severity, with diarrhea common in all treatment groups. Study discontinuation due to TEAEs was minimal (< 1%), and no discontinuations were related to RBX2660. There were no reported infections for which the causative pathogen was traced to RBX2660.

Conclusions: Across 5 clinical studies with consistent investigational product, RBX2660 was well tolerated in rCDI participants. In aggregate, these data provide compelling and consistent safety data for RBX2660.