Clostridium Difficile Infection
Conditions
Brief summary
Subjects will receive an oral dose of SER-109 in 4 capsules once daily for 3 consecutive days in Treatment Group I or matching placebo once daily for 3 consecutive days in Treatment Group II. The purpose of this study is to demonstrate the superiority of SER-109 vs placebo to reduce recurrence of CDI as determined by a toxin assay in adults up to 8 weeks after initiation of treatment.
Detailed description
ECOSPOR III is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of the safety, tolerability, and efficacy of SER-109 versus placebo in adult subjects 18 years of age or older with recurrent CDI, defined as: a history of ≥ 3 CDI episodes within 12 months, inclusive of the current episode. This study is designed to demonstrate the superiority of SER-109 versus placebo to reduce recurrence of Clostridium difficile infection (CDI) in adults who have received antibacterial drug treatment for recurrent CDI (RCDI), based on the proportion of subjects experiencing a CDI recurrence requiring antibiotic treatment up to 8 weeks after initiation of treatment. Approximately 188 subjects with a history of CDI, diarrhea and a positive C. difficile toxin test result on a stool sample, who have responded to standard-of-care (SOC) antibiotic treatment will be enrolled. Subjects will be randomly assigned, in a 1:1 ratio, to 1 of 2 treatment groups (Treatment Group I \[SER-109\] or Treatment Group II \[Placebo\]) and stratified by age (\<65 years; ≥65 years), as well as antibiotic regimen for the qualifying episode (vancomycin; fidaxomicin). Subjects will receive an oral dose of SER-109 in 4 capsules once daily for 3 consecutive days in Treatment Group I or matching placebo once daily for 3 consecutive days in Treatment Group II. Subjects with confirmed CDI recurrence, as defined in the Protocol, up to 8 weeks after administration of SER-109 or placebo treatment, may be eligible to enroll in the open-label SER-109 extension study (Study SERES-013).
Interventions
BIOLOGICALSER-109
SER-109 is an ecology of bacteria in spore form, enriched from stool donations obtained from healthy, screened donors Other Names: Eubacterial Spores, Purified Suspension, Encapsulated
DRUGPlacebo
Placebo will be identical to the investigational product but will not contain product spores or non-spore solids. Placebo will consist of 92% glycerol and 8% normal saline(0.9%).
Sponsors
Seres Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Signed informed consent prior to initiation of any study-specific procedure or treatment. The subject or their legally authorized representative must be able to provide written informed consent and understand the potential risks and benefits from study enrollment and treatment. 2. Male or female subject ≥ 18 years of age. 3. A qualifying episode of CDI as defined by: 1. ≥ 3 unformed stools per day for 2 consecutive days 2. A positive C. difficile stool toxin assay. 3. The requirement of CDI SOC antibiotic therapy (defined as 10 to 21 days of treatment with vancomycin \[125 mg QID\] and/or fidaxomicin \[200 mg BID\]). 4. An adequate clinical response following SOC antibiotic therapy, defined as (\<3 unformed stools in 24 hours) for 2 or more consecutive days before randomization. Main
Exclusion criteria
1. Female subjects who are pregnant, breastfeeding, lactating, or planning to become pregnant during the study. 2. Known or suspected toxic megacolon and/or known small bowel ileus. 3. Admitted to or expected to be admitted to an intensive care unit for medical reasons (not just boarding). Note: nursing homes, rehabilitation, assisted living centers and acute care hospitals are acceptable. 4. Absolute neutrophil count of \<500 cells/ml\^3 5. Major gastrointestinal surgery (e.g. significant bowel resection or diversion) within 3 months before enrollment (this does not include appendectomy or cholecystectomy), or any history of total colectomy or bariatric surgery (bariatric surgery which does not disrupt the gastrointestinal lumen, i.e., restrictive procedures such as banding, are permitted). 6. History of active inflammatory bowel disease (ulcerative colitis, Crohn's disease, microscopic colitis) with diarrhea believed to be caused by active inflammatory bowel disease in the past 3 months. 7. Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy (subjects on maintenance chemotherapy may only be enrolled after consultation with the study medical monitor). 8. Any history of fecal microbiota transplantation (FMT) within the previous 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence of CDI up to 8 Weeks | Up to Week 8 | Recurrence of CDI up to 8 Weeks after initiation of treatment. Recurrence was determined by stool Clostridioides difficile toxin assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence of CDI up to 4, 12 and 24 Weeks | Up to 4, 12 and 24 weeks after treatment | Recurrence of CDI up to 4, 12 and 24 Weeks after initiation of treatment. Recurrence was determined by stool Clostridioides difficile toxin assay. |
Countries
Canada, United States
Participant flow
Recruitment details
Overall, there were 51 sites in the United States and 5 sites in Canada that enrolled participants between 2017 to 2020.
Participants by arm
| Arm | Count |
|---|---|
| SER-109 Randomized to SER-109 arm. Assigned to receive SER-109 oral dose of 4 capsules once daily for 3 consecutive days. | 89 |
| Placebo Randomized to matching Placebo arm. Assigned to receive Placebo oral dose of 4 capsules once daily for 3 consecutive days. | 93 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Lack of Efficacy | 4 | 27 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 8 |
Baseline characteristics
| Characteristic | SER-109 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 16.5 | 65.5 years STANDARD_DEVIATION 16.7 | 65.5 years STANDARD_DEVIATION 16.5 |
| Antibiotic regimen for qualifying episode Fidaxomicin | 25 Participants | 24 Participants | 49 Participants |
| Antibiotic regimen for qualifying episode Vancomycin | 64 Participants | 69 Participants | 133 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 5 Participants | 6 Participants | 11 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 84 Participants | 87 Participants | 171 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 82 Participants | 88 Participants | 170 Participants |
| Sex: Female, Male Female | 60 Participants | 49 Participants | 109 Participants |
| Sex: Female, Male Male | 29 Participants | 44 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 90 | 0 / 92 |
| other Total, other adverse events | 77 / 90 | 79 / 92 |
| serious Total, serious adverse events | 15 / 90 | 19 / 92 |
Outcome results
Primary
Recurrence of CDI up to 8 Weeks
Recurrence of CDI up to 8 Weeks after initiation of treatment. Recurrence was determined by stool Clostridioides difficile toxin assay.
Time frame: Up to Week 8
Population: All participants who were randomly assigned, including those who were not exposed to any study drug, were analyzed based on the treatment to which they were randomly assigned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SER-109 | Recurrence of CDI up to 8 Weeks | 11 Participants |
| Placebo | Recurrence of CDI up to 8 Weeks | 37 Participants |
p-value: <0.00195% CI: [0.18, 0.58]Cochran-Mantel-Haenszel
Secondary
Recurrence of CDI up to 4, 12 and 24 Weeks
Recurrence of CDI up to 4, 12 and 24 Weeks after initiation of treatment. Recurrence was determined by stool Clostridioides difficile toxin assay.
Time frame: Up to 4, 12 and 24 weeks after treatment
Population: All participants who were randomly assigned, including those who were not exposed to any study drug, were analyzed based on the treatment to which they were randomly assigned.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SER-109 | Recurrence of CDI up to 4, 12 and 24 Weeks | CDI Recurrence-Week 4 | 10 Participants |
| SER-109 | Recurrence of CDI up to 4, 12 and 24 Weeks | CDI Recurrence-Week 12 | 16 Participants |
| SER-109 | Recurrence of CDI up to 4, 12 and 24 Weeks | CDI Recurrence-Week 24 | 19 Participants |
| Placebo | Recurrence of CDI up to 4, 12 and 24 Weeks | CDI Recurrence-Week 4 | 31 Participants |
| Placebo | Recurrence of CDI up to 4, 12 and 24 Weeks | CDI Recurrence-Week 12 | 43 Participants |
| Placebo | Recurrence of CDI up to 4, 12 and 24 Weeks | CDI Recurrence-Week 24 | 44 Participants |
Comparison: CDI recurrence rates at Week 4p-value: <0.00195% CI: [0.19, 0.67]Cochran-Mantel-Haenszel
Comparison: CDI recurrence rates at Week 12p-value: <0.00195% CI: [0.24, 0.65]Cochran-Mantel-Haenszel
Comparison: CDI recurrence rates at Week 24p-value: <0.00195% CI: [0.3, 0.73]Cochran-Mantel-Haenszel