Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI
Colleen S. Kraft, Matthew Sims, Michael Silverman, Thomas J. Louie, Paul Feuerstadt, Edward S. Huang, Sahil Khanna, Charles S. Berenson, Elaine E. L. Wang, Stuart H. Cohen, Louis Korman, Christine Lee, Colleen R Kelly, Alberto Odio, Paul P. Cook, Bret Lashner, Mayur Ramesh, Princy Kumar, Ananya De, Aslı Memişoğlu, David A. Lombardi, Brooke R. Hasson, Barbara H. McGovern, Lisa Von Moltke, Darrell S. Pardi, on behalf of the ECOSPOR III and ECOSPOR IV investigators, Anmar Hemaidan, Bharat Misra, Richard Nathan, Hien Nguyen, John Pullman, Jeffrey G. Williams, Idalia Acosta, Huy Tran, Kent Smith, Leonard B. Weinstock, Val Hansen, Michael Georgetson, Aasim Sheikh, Julia Garcia‐Diaz, Calin Arimie, Gladys Andrade, Steven O’Marro, Tuba Esfandyari, Timothy E. Ritter, Ian Mcnicol Baird, Ronald Colman, Meenakshi Patel, Lilliam Hernandez, Atoya Adams, Marie Walton, Razvan Arsenescu, Max Shapiro, Marvin Heuer, Tatiana Bogdanovich, Doria Grimard, Theodore S. Steiner, Debra Butt, Peter Daley, Stephanie Gauthier, Chantal Guímont, Leonard B. Weinstock, Michael Kreines, Larry Berman, Michael Bennett, Ronald Fogel, Juan Carlos Moises Gutierrez, P.C. Pedersen, Adam Bressler, Venkatesh Nadar, Eric Newton, Jorge Díaz, Jalal Abbas, Herbert L. DuPont, Aamir Jamal, Neetu Talreja, Sabrina Benjamin, Kamran Ayub, Godson Oguchi, Jose Pinero, Gowrappala Ramesh, Paul S. Sepe, Loren Brook, Frederick Ruthardt, Lindsey Surace, Ayub Hussain, Travis J. Rutland, Michael J. Schmalz, Gourisankar Degala, Raymond E. Phillips, Kent Stock, Jeffrey Bullock, Kenolisa Onwueme, Kenneth M. Johnson, Suzy Kim, Edward Portnoy, Scott Wofford, John Gancayco, Yoav Golan, Charles F. Barish
Abstract
INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI. OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities. METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24. RESULTS: TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6-13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression. CONCLUSIONS: VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03183128 and NCT03183141.