LB2 - (LATE-BREAKING ABSTRACT) An Investigational Oral Microbiome Drug, CP101, for the Prevention of Recurrent C. difficile Infection: A Randomized, Placebo-Controlled, Multi-Center Trial (PRISM3)
Jessica R. Allegretti, MD, MPH1, Colleen R. Kelly, MD, FACG2, Thomas Louie, MD3, Monika Fisher, MD, MSc4, Susy Hota, MD, MSc5, Bharat Misra, MD6, Nicholas W Van Hise, PharmD7, Eugene Yen, MD8, Jeff S. Bullock, MD9, John Pullman, MD10, Michael Silverman, MD11, Ian Davis, MD12, Sarah McGill, MD, MS13, Shrish Budree, MD14, Sahil Khanna, MBBS15, Darrell Pardi, MD15, Robert Orenstein, DO16, Ari Grinspan, MD17, Najwa El-Nachef, MD18, Colleen Kraft, MD19, Thomas J. Borody, MD, PhD, DSc, FACG20, Zain Kassam, MD, MPH14; 1Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 2Warren Alpert Medical School of Brown University and Center for Women's Gastrointestinal Medicine, Providence, RI, 3University of Calgary, Calgary, Alberta, Canada, 4Indiana University, Indianapolis, IN, 5University of Toronto and University Health Network, Toronto, Ontario, Canada, 6Borland Groover Clinic, Jacksonville, FL, 7Metro Infectious Disease Consultants, Burr Ridge, IL, 8NorthShore University Health System, Evanston, IL, 9Southern Star Research Institute, San Antonio, TX, 10Mercury Street Medical, Butte, MT, 11St. Joseph's Health Care and Western University, London, Ontario, Canada, 12Dalhousie University, Halifax, Nova Scotia, Canada, 13University of North Carolina Hospitals, Chapel Hill, NC, 14Finch Therapeutics, Somerville, MA, 15Mayo Clinic, Rochester, MN, 16Mayo Clinic, Scottsdale, AZ, 17Mount Sinai Hospital, New York, NY, 18University of California San Francisco, San Francisco, CA, 19Emory University Hospital, Atlanta, GA, 20Center for Digestive Diseases, Sydney, Australia
Introduction: Recurrent Clostridioides difficile infection (CDI) is common following CDI antibiotics and disruption of the gut microbiome is key to pathogenesis. There is a paucity of placebo-controlled trials assessing oral microbiome therapeutics. This study evaluated CP101, an investigational oral microbiome drug designed to restore microbiome diversity and prevent CDI recurrence in a broad population. Methods: We conducted a double-blind, randomized, placebo-controlled trial involving adults who received standard-of-care (SOC) antibiotics for recurrent CDI at 51 sites in the U.S. and Canada. 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 methods (PCR-based or Toxin EIA-based testing). Following completion of the most recent course of CDI antibiotics, eligible participants were randomized 1:1 to receive one-time oral administration of CP101 (6x1011 cell count) or placebo. The primary endpoint was sustained clinical cure, defined as an absence of CDI recurrence through week 8 following dosing. Results: 198 enrolled participants were analyzed with 27.5% of participants having one CDI recurrence prior to study entry and 62.7% of the qualifying CDI episodes diagnosed by PCR-based testing. Baseline characteristics were similar between CP101 (n=102) or placebo (n=96) arms (Table 1). Following SOC antibiotics, the proportion of sustained clinical cure was significantly higher with CP101 than placebo (relative risk reduction (RRR) 21%; 74.5% [76/102] vs 61.5% [59/96], p=0.0488]. In a per-protocol analysis determined prior to unblinding (n=166), sustained clinical cure was also significantly higher with CP101 than placebo (RRR 33%; 73.5% [61/83] vs 55.4% [46/83], p=0.0150). Time-to-event analysis showed a statistically significant benefit, favoring CP101 compared to placebo (p=0.0139) (Figure 1). CP101 was well-tolerated and there were no treatment-related serious adverse events. Conclusion: This is the largest randomized, placebo-controlled trial of an investigational oral microbiome drug. Following any SOC antibiotic course, CP101 resulted in a significant and clinically meaningful reduction in recurrent CDI compared to placebo. Importantly, CP101 resulted in the prevention of recurrence across a broad population, including patients with first CDI recurrence and diagnosis by any guideline approved CDI diagnostic method.Allegretti_Table_1.jpg width='440'>
Table 1: Clinical and Demographic Characteristic Allegretti_Figure_1.jpg width='440'>
Figure 1: Kaplan-Meier plot of time-to-CDI recurrence
