Durable reduction of Clostridioides difficile infection recurrence and microbiome restoration after treatment with RBX2660: results from an open-label phase 2 clinical trial

• Published in: BMC infectious diseases 2022-03, Vol.22 (1), p.245-245, Article 245
• Main Authors: Orenstein, Robert, Dubberke, Erik R, Khanna, Sahil, Lee, Christine H, Yoho, David, Johnson, Stuart, Hecht, Gail, DuPont, Herbert L, Gerding, Dale N, Blount, Ken F, Mische, Sarah, Harvey, Adam
• Format: Article
• Language: English
• Subjects: Clinical trial; Clostridioides difficile; Clostridium infections; Clostridium Infections - therapy; Control; Diseases; Drug discovery; Durability; Fecal Microbiota Transplantation - adverse effects; Fecal Microbiota Transplantation - methods; Humans; Identification and classification; Methods; Microbiota; Microbiota (Symbiotic organisms); Microbiota-based therapy; Neoplasm Recurrence, Local; Prevention; Prospective Studies; Recurrence; Relapse; Response; Retrospective Studies; Risk factors
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-022-07256-y

Effective treatment options for recurrent Clostridioides difficile infection (rCDI) are limited, with high recurrence rates associated with the current standard of care. Herein we report results from an open-label Phase 2 trial to evaluate the safety, efficacy, and durability of RBX2660-a standardized microbiota-based investigational live biotherapeutic-and a closely-matched historical control cohort. This prospective, multicenter, open-label Phase 2 study enrolled patients who had experienced either ≥ 2 recurrences of CDI, treated by standard-of-care antibiotic therapy, after a primary CDI episode, or ≥ 2 episodes of severe CDI requiring hospitalization. Participants received up to 2 doses of RBX2660 rectally administered with doses 7 days apart. Treatment success was defined as the absence of CDI diarrhea without the need for retreatment for 8 weeks after completing study treatment. A historical control group with matched inclusion and exclusion criteria was identified from a retrospective chart review of participants treated with standard-of-care antibiotics for recurrent CDI who matched key criteria for the study. The primary objective was to compare treatment success of RBX2660 to the historical control group. A key secondary outcome was the safety profile of RBX2660, including adverse events and CDI occurrence through 24 months after treatment. In addition, fecal samples from RBX2660-treated participants were sequenced to evaluate microbiome composition and functional changes from before to after treatment. In this Phase 2 open-label clinical trial, RBX2660 demonstrated a 78.9% (112/142) treatment success rate compared to a 30.7% (23/75) for the historical control group (p