S157 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). Similar sustained response rates were demonstrated in participants categorized by sex, race, and number of prior CDI episodes. As shown in Table, 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. Conclusion: 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.Figure 1.: Sustained Clinical Response Across Demographic Subgroups Through 24 Months After RBX2660 Treatment Table 1. - Summary of Adverse Events Across Demographic Subgroups Through 24 Months After RBX2660 Treatment Adverse Events/Participants (%) Age Sex Race Number of Prior CDI Episodes < 65 Years ≥ 65 Years Female Male White Non-White ≤3 >3 Onset Interval N = 62 N = 87 N = 95 N = 54 N = 136 N = 13 N = 74 N =75 6-12 months 46/23 (37) 95/36 (41) 81/37 (39) 60/22 (41) 130/55 (40) 11/4 (31) 48/27 (36) 93/32 (43) 12-24 months 59/15 (24) 88/30 (34) 77/27 (28) 70/18 (33) 127/41 (30) 20/4 (31) 60/17 (23) 87/28 (37) Severity Mild 119/19 (30.6) 236/12 (13.8) 288/21 (22.1) 147/10 (18.5) 395/30 (22.1) 40/1 (7.7) 217/17 (23.0) 218/14 (18.7) Moderate 87/22 (35.5) 155/27 (31.0) 134/41 (43.2) 108/8 (14.8) 215/43 (31.6) 27/6 (46.2) 113/21 (28.4) 129/28 (37.3) Severe 36/9 (14.5) 92/34 (39.1) 50/19 (20.0) 78/24 (44.4) 110/40 (29.4) 18/3 (23.1) 59/19 (25.7) 69/24 (32.0)