SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial
| Autor: | Christopher W.J. McChalicher, Amelia Tomlinson, Patricia Bernardo, Barbara H. McGovern, Matthew R. Henn, Roger J. Pomerantz, Jonathan Winkler, Madhumitha Nandakumar, Mary Jane Lombardo, Christopher A. Desjardins, Christopher B. Ford, Sunny S. Li, Sahil Khanna, Kevin Litcofsky, Elizabeth L. Hohmann, Darrell S. Pardi, Edward J. O’Brien, Jennifer R. Wortman, John G. Aunins, David N. Cook, Michele Trucksis |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.medical_specialty medicine.drug_class Antibiotics microbiome Placebo Gastroenterology 03 medical and health sciences 0302 clinical medicine Clostridioides Internal medicine Statistical significance medicine Humans Dosing Adverse effect Bile acid Clostridioides difficile business.industry Microbiota fecal microbiota transplantation dysbiosis Drugs Investigational Clinical trial Major Articles and Commentaries Diarrhea AcademicSubjects/MED00290 030104 developmental biology Infectious Diseases Clostridioides difficile infection Clostridium difficile diagnostics Clostridium Infections 030211 gastroenterology & hepatology medicine.symptom business |
| Zdroj: | Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America |
| ISSN: | 1537-6591 1058-4838 |
| Popis: | Background Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs. Methods In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (< or ≥65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing. Safety, C. difficile–positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed. Results 89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo (44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects ≥65 years (45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11–2.81), while the In a phase 2 trial, SER-109, an investigational microbiome drug, did not reduce rates of recurrent CDI, despite a previously successful open-label study. Key contributing factors, which led to a redesign of the currently enrolling phase 3 trial, are highlighted. |
| Databáze: | OpenAIRE |
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