The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial. (April 2021)

• Record Type: Journal Article
• Authors: Kao, Dina; Wong, Karen; Franz, Rose; Cochrane, Kyla; Sherriff, Keith; Chui, Linda; Lloyd, Colin; Roach, Brandi; Bai, Anthony D; Petrof, Elaine O; Allen-Vercoe, Emma
• Is Part Of: Lancet gastroenterology and hepatology. Volume 6:Number 4(2021)
• Page Start: 282
• Page End: 291
• Publication Date: 2021-04
• DOI: 10.1016/S2468-1253(21)00007-8
• Languages: English
• ISSNs: 2468-1253

Abstract

Summary: Background: Faecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection but has inherent risks. Microbial Ecosystem Therapeutic 2 (MET-2) is an oral encapsulated formulation of 40 lyophilised bacterial species initially isolated from stool of a healthy donor, but subsequently manufactured independently of donors, eliminating potential risks introduced by changes in donor health. The aim of this study was to determine MET-2 activity, safety, and tolerability. Methods: This phase 1, open-label, single-group feasibility study was done in Alberta, Canada. The main inclusion criteria were mild to moderate C difficile infection and at least one episode of C difficile infection recurrence (ie, two episodes of C difficile infection) within 12 months. Initial daily treatment was ten oral capsules for 2 days, then three capsules for 8 days. If C difficile infection recurred, a higher dose was offered: 20 capsules for 2 days, then three capsules for 8 days. Patients were followed for adverse events and C difficile infection recurrence up to day 130. The primary outcome was absence of C difficile infection recurrence (fewer than three unformed bowel movements in 24 h persisting for at least 2 days) at day 40 by intention-to-treat analysis. Secondary outcomes were mortality or hospitalisation due to C difficile infection, infections attributed to treatment, nausea, abdominal pain, vomiting, or diarrhoea during treatment, quality of life ( C difficile Health Related Quality of Life Questionnaire) before and after treatment, and engrafted MET-2 bacteria in patient stool. Absence of C difficile infection recurrence at day 130 was an exploratory outcome. This study is registered with ClinicalTrials.gov, NCT02865616 Findings: Between Sept 19, 2018, and Feb 28, 2020, we enrolled 19 adult patients with at least two episodes of mild to moderate C difficile infection (median age 65 years [IQR 56–67]; 12 women [63%], seven men [37%]). Recurrent C difficile infection was absent at day 40 in 15 (79%) of 19 patients after initial treatment, increasing to 18 (95%) 40 days after retreatment. No mortality associated with C difficile infection, infections associated with MET-2 treatment, or other serious adverse events were observed. The most common self-limited, mild to moderate symptoms reported during treatment were diarrhoea in 12 (63%) of 19 patients and abdominal cramps in 12 (63%). After MET-2 treatment, quality of life improved significantly, as did alpha diversity in stool microbial composition (p=1·93×10 −6 ). MET-2 associated taxa were found in greater abundance in most patients after treatment compared with baseline. 16 (84%) of 19 patients did not have recurrence of C difficile infection by day 130. Interpretation: MET-2 appears to be safe, efficacious, and well tolerated among patients with recurrent C difficile infection. Results must be validated in controlled studies. Funding: NuBiyota.