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

Authors

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
Asli Memisoglu
David A Lombardi
Brooke R Hasson
Barbara H McGovern
Lisa von Moltke
Darrell S Pardi
ECOSPOR III and ECOSPOR IV investigators

Publication Date

10-1-2024

Journal

Infectious Diseases and Therapy

DOI

10.1007/s40121-024-01007-z

PMID

38941068

PMCID

PMC11416444

PubMedCentral® Posted Date

6-28-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

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

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.

Comments

Trial Registration: ClinicalTrials.gov identifier, NCT03183128 and NCT03183141.

This article has been corrected. See Infect Dis Ther. 2024 Aug 30;13(10):2209.

Associated Data