RBX7455 - a Non-Frozen, Lyophilized, Oral Microbiota Reduces Clostridium difficileInfection Recurrence and Restores Patients‘ Microbiomes Presidential Poster Award

Abstract

Introduction: There is a need to standardize microbiota-based therapies for management of recurrent Clostridium difficile infection (rCDI). RBX7455 is a lyophilized, non-frozen, orally-administered microbiota-restoration therapy for rCDI. We present 8-week analysis of clinical safety, dose-finding and efficacy of a Phase 1 investigator-initiated open-label dose-finding trial of RBX7455 for preventing rCDI. Methods: Thirty patients with ≥2 CDI episodes were enrolled in three cohorts: 1) Four RBX7455 capsules twice daily for 4 days, n=10; 2) Four RBX7455 capsules twice daily for 2 days, n=10; 3) 2 RBX7455 capsules twice daily for 2 days, n=10. RBX7455 was administered 48 hours after finishing CDI antibiotics. Success was defined as absence of CDI recurrence (diarrhea and a positive stool test) through 8 weeks after treatment completion, and adverse events were monitored during and after treatment. Recipient stool samples prior to and at 1, 7, 30, and 60 days after treatment were collected. Stool and representative RBX7455 product samples were sequenced using an ultra-shallow shotgun sequencing method. Operational taxonomic unit (OTU) data were grouped by cohort and compared using a Bray-Curtis dissimilarity calculation. Relative OTU abundances at the class level were compared among time points. Results: Overall 30 patients with median age 63.8 years (range 21.9-83.1) and a median 2 (range 2-4) episodes of CDI were enrolled. Nine of ten patients in cohort 1, eight of ten patients in cohort 2, 10 of 10 patients in cohort 3 were recurrence-free at the 8-week endpoint, with an overall success rate of 90%. A total of 43 non-serious adverse events (AEs) have been recorded to date, with gastrointestinal AEs (transient constipation, abdominal discomfort and diarrhea) being most common. No serious AEs have been observed. Prior to treatment, the taxonomic compositions of responder microbiomes were significantly dissimilar from the RBX7455 composition and were dominated by Gammaproteobacteria and Bacilli. After treatment, patient microbiomes converged toward the RBX7455 composition, with Bacteroidia and Clostridia becoming more predominant. Microbiome changes were similar among responders from all cohorts. Conclusion: Three different dosing regimens of RBX7455 had a high success rate in preventing rCDI with no serious AEs. In addition, patient microbiomes converged toward the RBX7455 composition. Microbiome and safety data collection will continue for 6 months after treatment.