RBX7455, a Non-frozen, Orally Administered Investigational Live Biotherapeutic, Is Safe, Effective, and Shifts Patients' Microbiomes in a Phase 1 Study for Recurrent Clostridioides difficile Infections. (23rd September 2020)

• Record Type: Journal Article
• Authors: Khanna, Sahil; Pardi, Darrell S; Jones, Courtney; Shannon, William D; Gonzalez, Carlos; Blount, Ken
• Is Part Of: Clinical infectious diseases. Volume 73:Number 7(2021)
• Page Start: e1613
• Page End: e1620
• Publication Date: 2020-09-23
• Subjects: Clostridioides difficile infection -- recurrence -- microbiota-based therapeutic -- oral administration -- clinical trial; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa1430
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Recurrent Clostridioides difficile infections (rCDI) are a global public health threat. To reduce rCDI, microbiota-restoring therapies are needed, particularly standardized, easy-to-administer formulations. Methods: This phase I open-label trial assessed the safety, efficacy in preventing rCDI recurrence, and intestinal microbiome effects of RBX7455, a room temperature-stable, orally administered investigational live biotherapeutic. Adult participants with 1 or more prior episodes of rCDI received: 4 RBX7455 capsules twice daily for 4 days (group 1); 4 RBX7455 capsules twice daily for 2 days (group 2); or 2 RBX7455 capsules twice daily for 2 days (group 3). For all groups, the first dose was administered in clinic, with remaining doses self-administered at home. Adverse events were monitored during and for 6 months after treatment. Treatment success was defined as rCDI prevention through 8 weeks after treatment. Participants' microbiome composition was assessed prior to and for 6 months after treatment. Results: Nine of 10 group 1 patients (90%), 8 of 10 group 2 patients (80%), and 10 of 10 group 3 patients (100%) were recurrence-free at the 8-week endpoint with durability to 6 months. Seventy-five treatment-emergent adverse events were observed in 27 participants with no serious investigational product-related events. Prior to treatment, participants' microbiomes were dissimilar from the RBX7455 composition with decreased Bacteroidia- and Clostridia-class bacteria, whereas after treatment, responders' microbiomes showed increased Bacteroidia and Clostridia. Conclusions: Three dosing regimens of RBX7455 were safe and effective at preventing rCDI. Responders' microbiomes converged toward the composition of RBX7455. These results support its continued clinical evaluation. Clinical Trials Registration: NCT02981316. Abstract : In this open-label phase 1 study, 3 RBX7455 oral dosing regimens were safe and demonstrated an average of 90% efficacy at preventing recurrent Clostridioides difficile infections (rCDI). The intestinal microbiome of treatment responders was altered after treatment to resemble RBX7455 and known healthy populations.