PUNCH CD3-OLS: a phase 3 prospective observational cohort study to evaluate the safety and efficacy of fecal microbiota, live-jslm (REBYOTA) in adults with recurrent Clostridioides difficile infection.

Autor:	Feuerstadt P; Yale School of Medicine, New Haven, CT, USA., Chopra T; Wayne State University, Detroit, MI, USA., Knapple W; Arkansas Gastroenterology, North Little Rock, AR, USA., Van Hise NW; Metro Infectious Disease Consultants, Burr Ridge, IL, USA., Dubberke ER; Washington University School of Medicine, Saint Louis, MO, USA., Baggott B; Cleveland Clinic, Cleveland, OH, USA., Guthmueller B; Rebiotix Inc., a Ferring Company, Roseville, MN, USA., Bancke L; Rebiotix Inc., a Ferring Company, Roseville, MN, USA., Gamborg M; Ferring Pharmaceuticals, Copenhagen, Denmark., Steiner TS; Division of Infectious Diseases, University of British Columbia, Vancouver, BC, CA., Van Handel D; MNGI Digestive Health, Plymouth, MN, USA., Khanna S; Mayo Clinic, Rochester, MN, USA.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2024 Aug 24. Date of Electronic Publication: 2024 Aug 24.
DOI:	10.1093/cid/ciae437
Abstrakt:	Objective: To evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA) - the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the United States (US) Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment. Design: PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24-72h of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively. Results: Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups. Conclusions: RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date and findings support use of RBL to prevent rCDI in a broad patient population. Clinical Trial Registration: The study is registered at ClinicalTrials.gov (NCT03931941). (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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