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

Overview

Journal Infect Dis Ther

Specialty Infectious Diseases

Date 2024 Jun 28

PMID 38941068

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

Affiliations

Soon will be listed here.

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.

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