Background. There is increasing recognition that fecal transplant (FT) is an effective treatment for recurrent C. difficile infection (CDI). However, donor screening and product preparation can be burdensome. Despite promising efficacy results, safety data are limited. We report on a 60-day interim analysis of the first prospective open-label multi-center safety study of a next generation microbiota restoration therapy that has been standardized and manufactured under controlled conditions.
Methods. Patients with recurrent CDI, defined as at least 3 CDI episodes or at least 2 severe episodes resulting in hospitalization, were enrolled. All patients received treatment with RBX2660 (microbiota suspension) administered via enema. A second treatment was permitted if CDI recurred in < 8 weeks after the first treatment. Follow-up was at 7, 30 and 60 days and 3 and 6 months after the last treatment. The primary objective was the product-related adverse events (AEs). A secondary objective was CDI resolution.
Results. Of the 40 patients enrolled at 11 centers in the US, 34 patients (mean age 66.8 years, 67.6% female) received at least one treatment. Thirty-one patients were included in a 60-day interim analysis. A total of 158 AEs were elicited in 29 patients. AEs were predominantly mild to moderate and included flatulence, belching, constipation, and occasional bouts of diarrhea. There were 9 serious AEs reported in 6 patients (3 recurrent CDI ≤ 8 weeks days post-treatment, all of which required hospitalization; 1 case of pneumonia; 1 pelvic fracture; 1 stab wound; 1 chronic obstructive pulmonary disease; 1 pulmonary edema and 1 respiratory failure). None of the serious AEs was related to RBX2660 or its administration. Efficacy of RBX2660 defined as the absence of CDI at 8 weeks after the last dose was 87.1%.
Conclusion. RBX2660 was well-tolerated and demonstrated satisfactory safety in a 60-day interim analysis of the first prospective multi-center study of a next generation standardized, commercially prepared microbiota restoration therapy for recurrent CDI.
Disclosures. E. Dubberke, Rebiotix: Consultant and Investigator, Consulting fee and Research support; Sanofi Pasteur: Consultant and Investigator, Consulting fee and Grant recipient; Merck: Consultant and Grant Investigator, Consulting fee and Research support; Cubist: Consultant and Investigator, Consulting fee and Research support R. Orenstein, ReBiotix: Investigator and Scientific Advisor, Consulting fee and Research support; Merck: Consultant and Investigator, Research support P. Mariani, Rebiotix: Investigator, Research support K. Mullane, Rebiotix: Research Contractor, Research support; Astellas Pharma US Inc.: Research Contractor and Speaker's Bureau, Research support; Ason Pharmaceuticals: Research Contractor, Research support; Chimerix: Research Contractor and Scientific Advisor, Research support; Cubist/Optimer: Research Contractor and Scientific Advisor, Consulting fee and Research grant; Merck Sharp and Dohme Corp: Research Contractor and Scientific Advisor, Consulting fee and Research support; ViroPharma: Research Contractor, Research support; Pfizer: Research Contractor, Research support M. K. Sobcinski, Rebiotix Inc.: Employee, Salary