Week 24 Efficacy and Safety Data from PRISM3: A Randomized, Placebo-Controlled Trial Evaluating CP101, an Investigational Orally Administered Microbiome Therapeutic for the Prevention of Recurrent C. difficile Infection

Introduction: Disruption of the microbiome is key to pathogenesis of recurrent Clostridioides difficile infection (CDI). Placebo-controlled trials assessing microbiome therapeutics have demonstrated efficacy in recurrent CDI; however, there is a paucity of data on response durability and long-term safety. CP101 is an investigational orally administered microbiome therapeutic designed to restore microbiome diversity and enable early intervention in the management of recurrent CDI. Given its complete consortia composition, CP101 is hypothesized to have a durable effect. Methods: We conducted a double-blind, randomized, placebo-controlled trial (PRISM3) enrolling adults who received standard-of-care antibiotics for recurrent CDI. Patients with first CDI recurrence at high-risk for further recurrence (≥65 years), or those with two or more recurrences were eligible. The qualifying CDI episode was diagnosed prior to study entry by guideline recommended testing (PCR-based or toxin EIA-based). Following CDI antibiotics, eligible participants were randomized 1:1 to receive one-time oral administration of CP101 or placebo without bowel preparation. The primary efficacy endpoint was sustained clinical cure, defined as an absence of CDI recurrence through Week 8 following dosing. Secondary endpoints of efficacy and safety were evaluated through Week 24. Results: 198 enrolled participants were analyzed with 28.8% of participants having one CDI recurrence prior to study entry and 61.1% of the qualifying CDI episodes diagnosed by PCR-based testing. Baseline characteristics were similar between CP101 (n=102) and placebo (n=96) arms. As previously reported, the CP101 arm demonstrated a statistically significant and clinically meaningful improvement in sustained clinical cure compared to the placebo arm through Week 8. On long-term assessment, CP101 demonstrated clinically meaningful durability and the proportion of participants with sustained clinical cure through Week 24 remained significantly higher in the CP101 arm compared to placebo (73.5% [75/102] vs 59.4% [57/96], P=0.0347) (Fig. 1a). Time-to-event analysis through Week 24 showed a statistically significant and durable benefit, favoring CP101 compared to placebo (P=0.018) (Fig. 1b). Through Week 24, adverse events were similar across both arms, and no treatment-related SAEs were reported with CP101. Conclusion: On long-term assessment, CP101 demonstrated durable efficacy for the prevention of recurrent CDI and a safety profile similar to placebo through Week 24.Figure 1.: a. CP101 demonstrated durable efficacy for the prevention of recurrent CDI in PRISM3. b. CP101 demonstrated a durable effect over time compared to placebo in PRISM3.