E0100 - 24-Month Sustained Clinical Response and Safety of RBX2660 in Participants With Recurrent Clostridioides difficile Infection: Subgroup Analysis

Introduction: Clostridioides difficile is an opportunistic pathogen that causes an estimated 500,000 infections per year in the United States. Microbiota-based treatments have shown promise in reducing recurrent Clostridioides difficile infection (rCDI), but long-term efficacy and safety data have been reported infrequently. Here, we present a subgroup analysis on the long-term efficacy and safety of RBX2660, a microbiota-based live biotherapeutic, in participants with rCDI in PUNCH CD Open-Label (NCT02589847), a prospective, multicenter, open-label phase 2 trial.

Methods: PUNCH CD Open-Label participants enrolled between October 1, 2015, and March 6, 2017, were ≥18 years old with either ≥2 episodes of rCDI treated by standard-of-care antibiotic therapy after a primary CDI episode, or ≥2 episodes of severe CDI requiring hospitalization. All participants had a positive stool test for C. difficile or toxins within 60 days prior to enrollment and were on antibiotics to treat CDI at the time of enrollment. Participants received up to 2 doses of RBX2660 rectally administered 7 ± 2 days apart. Treatment success was defined as the absence of CDI diarrhea without the need for CDI retreatment for 8 weeks after completing study treatment. In this post hoc subgroup analysis, we report the 6-, 12-, and 24-month outcomes of 8-week responders by age, sex, race, and number of prior CDI episodes.

Results: Among the 142 participants treated with RBX2660 (evaluable population), 92% were white, 62% were female, 59% were ≥65 years of age, and 49% had >3 prior episodes of CDI. Sustained treatment response through 6-, 12-, and 24-months after treatment, respectively, was achieved by 98.0%, 97.9%, and 93.5% of participants < 65 years of age and by 96.8%, 93.1%, and 88.0% of participants ≥65 years of age (Figure 1). Similar sustained response rates were demonstrated in participants categorized by sex, race, and number of prior CDI episodes. As shown in Table 1, treatment-emergent adverse events (TEAEs) were reported by a similar percentage of participants across demographic subgroups between 6-12 months (range: 31% to 43%) and 12-24 months (range: 23% to 37%) after treatment with RBX2660, with most being gastrointestinal and mild to moderate in severity.

Discussion: Across demographic subgroups, the majority of RBX2660 responders showed a sustained clinical response, remaining free of CDI recurrence up to 24 months after treatment. Long-term safety data reinforce that RBX2660 is well-tolerated.