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

Infectious Diseases and Therapy, ISSN: 2193-6382, Vol: 13, Issue: 10, Page: 2105-2121
2024
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Article Description

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.

Bibliographic Details

Colleen S. Kraft; Matthew Sims; Michael Silverman; Thomas J. Louie; Paul Feuerstadt; Edward S. Huang; Sahil Khanna; Darrell S. Pardi; Charles S. Berenson; Elaine E.L. Wang; Ananya De; Asli Memisoglu; David A. Lombardi; Brooke R. Hasson; Barbara H. McGovern; Lisa von Moltke; Stuart H. Cohen; Louis Korman; Christine Lee; Colleen R. Kelly; Alberto Odio; Paul P. Cook; Bret Lashner; Mayur Ramesh; Princy Kumar; Shari E. Rozen; Feliz P. Tiongco; Dhaval Patel; Patricial Salvato; Marco Zahedi; Markian R. Bochan; John M. Joseph; Syed M. Rehman; Juan Sarol; Naval Parikh; John Hong; Larry E. Clark; Najwa El-Nachef; Eugene F. Yen; James A. Maher; Harold G. Preiksaitis; Babatunde Adeyafa; Sushma V. Gorrela; Kofi W. Nauako; Ankur A. Doshi; Roberto Fernandez; Rukan Daccak; George Dickstein; Vivaik Tyagi; Agadasah Kuliev; Maria Cubillas; Chad M. Gonzales; Ahmed A. Arif; Miguel E. Trevino; Yaneicy Gonzalez-Rojas; Harry Sarles; Eliot Godofsky; Pradeep Kumar Bekal; Zahid N. Zafar; Bruce Musgrave; Diane Carbonneau; John De Beixedon; Atsushi Skuraba; Emil Valle; David Dulitz; Myung Choi; Todd B. Ellerin; Chandar Singaram; Kenneth Boren; Shiwali Rai; Jason Wilson; Andrew Gentry; Allan G. Coates; Robert Brennan; Debra Powell; Satish Rao; Antonio Terrelonge; Anubha Gupta; Teresa Alfonso; Mousab Tabbaa; Shatishkumar Patel; Govinda Lohani; Syed Nasir Husain; Rodolfo Hanabergh; Bruce Branin; Sadia Dar; Ralf Gebhard; Mohammed Mazen Jamal; Matthew Parker; Ernest Hendrix; John Curran; Magued Beshay; Rizwana Thanawala; Robert Jaeger; Michael Galambos; Saad Jazrawi; Robert Orr; Ifzal Bangash; Mark Kogan; Ghassan Hadi; Jennifer Vincent; Raymond Mason; Sanjeev Kumar; Shalini Katikaneni; Alexander Dela Llana; Patricia Henry; Peter Higgins; Richard Black; Ravish Parekh; Charles Okolo; Alex Sherman; James Welker; Thomas Welton; Jeffrey Garber; Brian Behm; Lucky Flores; James Haaksma; Tariq Mehmood; Gail Hecht; Matthew Hall; Alfred Bacon; Jerry Stern; Olayemi Osiyemi; Jaynier Moya; Satinder Gill; Keith Friedenberg; Sebastian Stanciu; Subhash Gumber; Richard Caradonna; Syed Naqvi; Angelo Coppola; Michael Tan; Issa Ephtimios; Zeid Kayali; Benton Oubre; Jean Marie Houghton; Charles Barish; Yoav Golan; John Gancayco; Scott Wofford; Edward Portnoy; Suzy Kim; Kenneth Johnson; Kenolisa Onwueme; Jeffrey Bullock; Kent Stock; Raymond Phillips; Gourisankar Degala; Michael Schmalz; Travis Rutland; Ayub Hussain; Lindsey Surace; Frederick Ruthardt; Loren Brook; Paul Sepe; Gowrappala Ramesh; Jose Pinero; Godson Oguchi; Kamran Ayub; Sabrina Benjamin; Neetu Talreja; Aamir Jamal; Herbert DuPont; Jalal Abbas; Jorge Diaz; Eric Newton; Venkatesh Nadar; Adam Bressler; Peder Pedersen; Juan Carlos Moises Gutierrez; Ronald Fogel; Michael Bennett; Larry Berman; Michael Kreines; Leonard Weinstock; Chantal Guimont; Stephanie Gauthier; Peter Daley; Debra Butt; Theodore Steiner; Doria Grimard; Tatiana Bogdanovich; Marvin Heuer; Max Shapiro; Razvan Arsenescu; Marie Walton; Atoya Adams; Lilliam Hernandez; Meenakshi Patel; Ronald Colman; Ian Mcnicol Baird; Timothy Ritter; Tuba Esfandyari; Steven O’Marro; Gladys Andrade; Calin Arimie; Julia Garcia-Diaz; Aasim Sheikh; Michael Georgetson; Val Hansen; Kent Smith; Huy Tran; Idalia Acosta; Jeffrey Williams; John Pullman; Hien Nguyen; Richard Nathan; Bharat Misra; Anmar Hemaidan

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Medicine

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