Table 1.

Overview of Phase 1 study and ECOSPOR clinical trials.

Parameter	Phase 1 Study	ECOSPOR-II	ECOSPOR – III	ECOSPOR – IV
Study Design	Phase 1 open-label, single-arm, descending-dose study	Phase 2 multicenter, randomized, double blind, placebo controlled clinical study	Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study	Open-label extension and open-label programme study
Study Type	Standard design with expansion cohort	Interventional (Clinical trial)	Interventional (Clinical trial)	Interventional (Clinical trial)
No. of Study Participants	30 (15 received 1.7*109 spores for 2 consecutive days; 15 received 1.1*108 spores for 1 day)	89 (59 received SER-109; 30 received placebo)	182 (89 received SER-109; 93 received placebo)	263 (Cohort 1 - 29 rollover participants from ECOSPOR-III trial; Cohort 2 - 234 new participants. Both cohorts received SER-109 in four capsules once daily for three consecutive days)
Primary Purpose	Determine efficacy, dosage, and safety profile	Prevention	Treatment	Treatment
Time Period	Prior to 2015	2015 to 2016	2017 to 2020	2017 to 2022
Location	United States	United States	United States & Canada	United States & Canada
Primary Outcome	Prevention of recurrent CDI during the 8-week follow-up after SER-109	Number of subjects with CDI recurrence 8 weeks after treatment	Recurrence of CDI up to 8 weeks after initiation of treatment	For Cohort 1 - Recurrence of CDI up to 8 weeks after treatment For Cohort 2 - Recurrence of CDI up to 8 and 12 weeks after treatment
Main clinical findings	96.7% of participants achieved clinical resolution of recurrent CDI following SER-109 administration. A single patient required a second dose of SER-109 on day 26 of the study. Four patients (13%) experienced recurrence within the first 9 days of SER-109 administration with self-resolution in three patients. Microbial diversity increased significantly at 8 weeks with changes being observed as early as day 4 and as late as 24 weeks. SER-109 constituted 33% of total gut carriage followed by 32% of augmented non–SER-109 bacteria. Bacteroides and Parabacteroides were augmented with a decline in Klebsiella species. E. coli was the most abundant facultative gram-negative anaerobe.	No significant differences in CDI recurrence rates between the two groups (44.1% vs 53.3%; relative risk − 1.2; 95% CI − 0.8–1.9). Age stratification showed that in individuals ≥65 years old, SER-109 significantly reduced recurrence (45.2% vs 80%, respectively; relative risk −1.8; 95% CI − 1.1–2.8). However, in individuals younger than 65 years, no significant difference in recurrence rates were noted. No difference in time to recurrence between the groups. Notably, 50% of recurrences occurred within 11 days.	CDI recurrences were significantly lower in the SER-109 group than in the placebo group (12% and 40%, respectively; relative risk − 0.32; 95% CI − 0.18 to 0.58; P<0.001). Sustained clinical response at the end of week 8 was observed in 88% and 60% of participants in SER-109 and placebo groups, respectively. Both age stratification and antibiotic stratification (vancomycin vs. fidaxomicin) showed lower percentages of patients with CDI recurrence in the SER-109 group than the placebo group. 48 patients reported recurrences by week 8 with 75% cases occurring within 2 weeks and 85% within 4 weeks after administration of SER-109 or placebo. Gut microflora changes included decline in Enterobacteriaceae bacteria and increase in Firmicutes bacteria, such as Ruminococcaceae and Lachnospiraceae.	In cohort 1 (rollover) 13.8% of participants had recurrence compared with 8.1% in cohort 2 at the end of week 8. Furthermore, in cohort 2, 9.8% of participants developed recurrence at the end of week 12. Sustained clinical response was observed in 86.2% of cohort 1 participants compared with 91.9% of cohort 2 participants in cohort 2. Furthermore, in cohort 2, 90.2% of participants had reported sustained clinical response.
Reported Adverse Reactions	50% of patients developed mild to moderate adverse reactions related to SER-109. No difference was noted due to dosing differences. No deaths were noted.	67% of patients in SER-109 group reported mild to moderate adverse reactions compared to 69% in placebo group. A single patient died in the SER-109 group.	Serious adverse events were noted in 8% and 16% of participants in SER-109 and placebo group, respectively. Gastrointestinal disorders (mild to moderate in nature) were the most common adverse reactions − 88% in SER-109 group and 87% in placebo group.	All cause mortality was 0% and 3.4% in cohort 1 and 2, respectively. Serious adverse events were reported in 3.5% and 13.7% in cohort 1 and 2, respectively. 48.2% and 29.1% of participants in cohort 1 and 2, respectively, developed mild to moderate adverse reactions.
Trial NCT No.	Not applicable	NCT02437487	NCT03183128	NCT03183141