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

on behalf of the ECOSPOR III and ECOSPOR IV investigators

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2105-2121
Number of pages17
JournalInfectious Diseases and Therapy
Volume13
Issue number10
DOIs
StatePublished - Oct 2024

Funding

We would like to acknowledge the work of many contributors to this study and manuscript, including all the study investigators who made this trial possible. We would also like to acknowledge Genesis Research, LLC for their work in deriving Charlson Comorbidity Index scores. Finally, we are indebted to all the patients who participated in ECOSPOR\u00A0III and ECOSPOR\u00A0IV. ECOSPOR III and IV Investigators: Anmar Hemaidan, Bharat Misra, Richard Nathan, Hien Nguyen, John Pullman, Jeffrey Williams, Idalia Acosta, Huy Tran, Kent Smith, Leonard Weinstock, Val Hansen, Michael Georgetson, Aasim Sheikh, Julia Garcia-Diaz, Calin Arimie, Gladys Andrade, Steven O\u2019Marro, Tuba Esfandyari, Timothy 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 Steiner, Debra Butt, Peter Daley, Stephanie Gauthier, Chantal Guimont, Leonard Weinstock, Michael Kreines, Larry Berman, Michael Bennett, Ronald Fogel, Juan Carlos Moises Gutierrez, Peder Pedersen, Adam Bressler, Venkatesh Nadar, Eric Newton, Jorge Diaz, Jalal Abbas, Herbert DuPont, Aamir Jamal, Neetu Talreja, Sabrina Benjamin, Kamran Ayub, Godson Oguchi, Jose Pinero, Gowrappala Ramesh, Paul Sepe, Loren Brook, Frederick Ruthardt, Lindsey Surace, Ayub Hussain, Travis Rutland, Michael Schmalz, Gourisankar Degala, Raymond Phillips, Kent Stock, Jeffrey Bullock, Kenolisa Onwueme, Kenneth Johnson, Suzy Kim, Edward Portnoy, Scott Wofford, John Gancayco, Yoav Golan, Charles Barish, JeanMarie Houghton, Benton Oubre, Zeid Kayali, Magued Beshay, John Curran, Issa Ephtimios, Michael Tan, Angelo Coppola, Syed Naqvi, Richard Caradonna, Subhash Gumber, Sebastian Stanciu, Keith Friedenberg, Satinder Gill, Jaynier Moya, Olayemi Osiyemi, Jerry Stern, Alfred Bacon, Matthew Hall, Gail Hecht, Tariq Mehmood, James Haaksma, Lucky Flores, Brian Behm, Jeffrey Garber, Thomas Welton, James Welker, Alex Sherman, Charles Okolo, Ravish Parekh, Richard Black, Peter Higgins, Patricia Henry, Alexander Dela Llana, Shalini Katikaneni, Sanjeev Kumar, Raymond Mason, Jennifer Vincent, Ghassan Hadi, Mark Kogan, Ifzal Bangash, Robert Orr, Saad Jazrawi, Michael Galambos, Robert Jaeger, Rizwana Thanawala, Magued Beshay, John Curran, Ernest Hendrix, Matthew Parker, Mohammed Mazen Jamal, Ralf Gebhard, Sadia Dar, Bruce Branin, Rodolfo Hanabergh, Syed Nasir Husain, Govinda Lohani, Shatishkumar Patel, Mousab Tabbaa, Teresa Alfonso, Anubha Gupta, Antonio Terrelonge, Satish Rao, Debra Powell, Robert Brennan, Allan G. Coates, Andrew Gentry, Jason Wilson, Shiwali Rai, Kenneth Boren, Chandar Singaram, Todd B. Ellerin, Myung Choi, David Dulitz, Emil Valle, Atsushi Skuraba, John De Beixedon, Diane Carbonneau, Bruce Musgrave, Zahid N. Zafar, Pradeep Kumar Bekal, Eliot Godofsky, Harry Sarles, Yaneicy Gonzalez-Rojas, Miguel E. Trevino, Ahmed A. Arif, Chad M. Gonzales, Maria Cubillas, Agadasah Kuliev, Vivaik Tyagi, George Dickstein, Rukan Daccak, Roberto Fernandez, Ankur A. 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 Hong, Naval Parikh, Juan Sarol, Syed M. Rehman, John M. Joseph, Markian R. Bochan, Marco Zahedi, Patricial Salvato, Dhaval Patel, Feliz P. Tiongco, Shari E. Rozen. The ECOSPOR III and ECOSPOR IV studies were funded by Seres Therapuetics. The Rapid Service Fee was funded by Seres Therapeutics and Nestle Health Science. Contributors from Seres Therapeutics were responsible for the design and conduct of the studies; the collection, management, analysis, and interpretation of the data; and the preparation, review, and approval of the manuscript.

Keywords

  • Clostridioides difficile infection
  • Microbiome
  • Microbiome therapeutics
  • Recurrent C. difficile infection

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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