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

Sahil Khanna, Darrell S Pardi, Courtney Jones, William D Shannon, Carlos Gonzalez, Ken Blount, Sahil Khanna, Darrell S Pardi, Courtney Jones, William D Shannon, Carlos Gonzalez, Ken Blount

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.

Keywords: Clostridioides difficile infection; clinical trial; microbiota-based therapeutic; oral administration; recurrence.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Consort diagram showing participant enrollment, allocation, follow-up, and analysis. Abbreviation: rCDI, recurrent Clostridioides difficile infection.
Figure 2.
Figure 2.
Nonparametric multidimensional similarity analysis for microbiome compositions of RBX7455 (Prod) and participant microbiome compositions before treatment (BL) and 1 day (1D) or 1, 4, 8, 12, and 24 weeks (1W, 4W, 8W, 12W, and 24W) after treatment.
Figure 3.
Figure 3.
Taxonomic compositions at the class level and alpha diversity of responder microbiomes and RBX7455. Relative abundance data are shown in box-and-whiskers format, and alpha diversity is shown as a mean with standard deviations. Classes with

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