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

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.