Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI.
Document Type
Article
Publication Date
6-28-2024
Publication Title
Infect Dis Ther
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.
Volume
Online ahead of print
Recommended Citation
Kraft CS, Sims M, Silverman M, Louie TJ, Feuerstadt P, Huang ES et al. Integrated safety and efficacy analyses of phase 3 trials of a microbiome therapeutic for recurrent CDI. Infect Dis Ther. 2024 Jun 28. doi: 10.1007/s40121-024-01007-z. Epub ahead of print. Erratum in: Infect Dis Ther. 2024 Aug 30. doi: 10.1007/s40121-024-01036-8. PMID: 38941068.
DOI
10.1007/s40121-024-01007-z
ISSN
2193-8229
PubMed ID
38941068