D0100 - Efficacy and Safety of RBX2660 in Patients After First Recurrence of Clostridioides difficile Infection – Results From a Phase 3, Randomized, Placebo-Controlled Study

Introduction: Antibiotics used to treat Clostridioides difficile infection (CDI) can predispose patients to recurrent CDI (rCDI). Gut microbiome restoration by fecal microbiota transplantation is recommended by multiple guidelines after ≥2 rCDI, with no guideline recommended options to restore the microbiome earlier in the course of CDI. A prespecified analysis of a prospective, multicenter, randomized, double-blind, placebo-controlled phase 3 trial, PUNCH CD3 (NCT03244644), showed consistent efficacy of microbiota-based live biotherapeutic RBX2660 in participants with ≤3 (treatment success: placebo, 67%; RBX2660, 72%) and >3 (placebo, 54%; RBX2660, 70%) episodes of CDI prior to enrollment. In the present post-hoc analysis, we report the efficacy and safety of RBX2660 in a subgroup of patients with only 1 rCDI episode prior to enrollment.

Methods: Patients enrolled in PUNCH CD3 were ≥18 years old with ≥1 rCDI episode as determined by the treating physician and assessed with current standard-of-care (SOC) diagnostic methods. After completing SOC antibiotic therapy for the enrolling CDI episode, patients received a single blinded dose of RBX2660 or placebo. Treatment success was defined as remaining free of CDI recurrence for 8 weeks after treatment. Patients were monitored for recurrence through 6 months. Treatment-emergent adverse events (TEAEs) were summarized for the double-blind treatment period within 8 weeks.

Results: In the modified intent-to-treat population, 86 of 276 patients (32.2%) were enrolled after 1 rCDI. Patients were mostly white (93%) and female (66.3%) with a mean age of 58 years. At week 8, 79.2% (42/53) of RBX2660-treated patients and 60.6% (20/33) of placebo-treated patients achieved treatment success. Of responders, 90.5% (38/42) treated with RBX2660 and 85% (17/20) treated with placebo remained recurrence-free at 6 months. TEAEs were reported by 54.7% (29/53) of RBX2660-treated patients and 33.3% (11/33) of placebo-treated patients; mild events, mostly gastrointestinal, accounted for the difference. Serious adverse events were reported by 5.7% (3/53) of RBX2660-treated and 6.1% (2/33) of placebo-treated patients. No potentially life-threatening TEAEs or TEAEs leading to discontinuation or death were reported.

Discussion: After 1 rCDI episode, RBX2660-treated patients had numerically higher treatment success at week 8 and sustained response at 6 months compared to placebo. These results support the efficacy and safety of RBX2660 in reducing rCDI.