Background: Clostridioides difficile infection (CDI) is a leading healthcare-associated infection causing debilitating diarrhea, life-threatening complications, 20,500 deaths and healthcare costs of up to $5.4 billion annually in the US. The main driver of CDI costs is hospitalizations, and patients with higher CDI recurrence rates have more hospitalizations and emergency department visits and longer hospital stays. We previously reported that SER-109, an investigational oral microbiome therapeutic, was superior to placebo in reducing CDI recurrence rates at 8 weeks after dosing in adults with rCDI infection (NCT03183128). Here, we report CDI-related and non-related hospitalizations in adults with rCDI.

Methods: Adults with rCDI (≥3 episodes in 12 months) were screened at 56 US/Canadian sites. After completing standard-of-care antibiotics, subjects with symptom resolution were randomized 1:1 to SER-109 (4 capsules x 3 days) or matching placebo. The primary and secondary endpoints were rCDI (recurrent toxin+ diarrhea requiring treatment [investigator decision]) at 8 weeks and up to 24 weeks posttreatment, respectively. Exploratory endpoints included cumulative incidence of hospitalizations up to 24 weeks posttreatment.

Results: 281 subjects were screened and 182 were randomized (59.9% female; mean age 65.5 years). Most were outpatients in the community (90.7% home-dwelling; 7.1% assisted living; 1.1% rehabilitation facility; 1.1% inpatient). A lower proportion of SER-109 treated subjects had rCDI after dosing compared to placebo at Weeks 4, 8, 12 and 24 (P< 0.001 at all timepoints; Table 1). Overall, 36 subjects were hospitalized over 24 weeks (15 subjects in the SER-109 arm and 21 in the placebo arm [Table 2]). Nine subjects (25%) were hospitalized due to CDI (2 subjects in the SER-109 arm and 7 subjects in the placebo arm). Fewer subjects in the SER-109 arm were hospitalized compared to the placebo arm at all time points for both all cause and CDI-related hospitalizations. Overall, the majority of subjects with hospitalization events (63.9%) were hospitalized within the first 8 weeks after treatment.

Conclusions: During the 24-week ECOSPOR III study period, a lower incidence of both all-cause and CDI-related hospitalizations was observed in the SER-109 arm compared to the placebo arm in this mostly outpatient population. These data suggest a potential benefit of SER-109 treatment in reducing hospitalizations and thus lowering the burden of rCDI on the healthcare system.

IMAGE 1: Table 1. Cumulative C. difficile infection recurrence rates, rate differences, and relative risks at various timepoints in ITT population

IMAGE 2: Table 2. Cumulative Hospitalization by Hospitalization Reason, ITT Population