Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI

作者：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, JeanMarie Houghton, Benton Oubre, Zeid Kayali, Magued Beshay, John Curran, Issa Ephtimios, Michael J. Tan, Angelo Coppola, Syed Naqvi, Richard Caradonna, Subhash Gumber, Sebastian Stanciu, Keith Friedenberg, Satinder Gill, Jaynier Moya, Olayemi Osiyemi, Jerry Stern, Alfred E. Bacon, Matthew Hall, Gail Hecht, Tariq Mehmood, James Haaksma, Lucky Flores, Brian Behm, Jeffrey R. Garber, Tom Welton, James Welker, Alex Sherman, Charles Okolo, Ravish Parekh, R.A. Black, Peter Higgins, Patricia Henry, Alexander Dela Llana, Shalini Katikaneni, Sanjeev Kumar, R. MASON, Jennifer Vincent, Ghassan J. Hadi, М. М. Коган, Ifzal Bangash, Robert D. Orr, Saad F. Jazrawi, Michael Galambos, R. Jaeger, Rizwana Thanawala, Magued Beshay, John Curran, Ernest Hendrix, Matthew E. Parker, Mohammed Mazen Jamal, Ralf E. Gebhard, Sadia Dar, Bruce Branin, Rodolfo Hanabergh, Syed Nasir Husain, Govinda Lohani, Shatishkumar Patel, Mousab Tabbaa, Teresa Alfonso, Anubha Gupta, Antonio Terrelonge, Satish S.C. Rao, D. C. Powell, Robert P. Brennan, Allan Coates, Andrew Donald Gentry, Jason Wilson, Shiwali Rai, Kenneth Boren, Chandar Singaram, Todd B. Ellerin, Myung Chul Choi, David Dulitz, Emil Valle, Atsushi Skuraba, John De Beixedon, Diane Carbonneau, Bruce Musgrave, Zahid N. Zafar, Pradeep Bekal, Eliot Godofsky, H Sarles, Yaneicy Gonzalez‐Rojas, Miguel E. Trevino, Ahmed A. Arif, Chad M. Gonzales, Maria Cubillas, A.A. Kuliev, Vivaik Tyagi, George Dickstein, Rukan Daccak, Roberto Fernandez, Ankur Doshi, Kofi W. Nauako, Sushma V. Gorrela, Babatunde Adeyafa, Harold G. Preiksaitis, James A. Maher, Eugene F. Yen, Najwa El‐Nachef, Larry E. Clark, John J. Hong, Naval Parikh, Juan Sarol, Syed M. Rehman, John Joseph, Markian R. Bochan, Marco Zahedi, P Salvato, Dhaval Patel, F Tiongco, Shari E. Rozen · 发表于：Infectious Diseases and Therapy · 年份：2024 · DOI：10.1007/s40121-024-01007-z · 被引用次数：8 · 研究领域：Clostridium difficile and Clostridium perfringens research、Nosocomial Infections in ICU、Helicobacter pylori-related gastroenterology studies

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 in...