Clostridioides Difficile Infection
Conditions
Keywords
Clostridioides infection, Gastrointestinal Diseases, Digestive System Diseases, Intestinal Diseases, Gram-Positive Bacterial Infections, Communicable Diseases
Brief summary
Cohort 1: Subjects who had a Clostridioides difficile infection (CDI) recurrence in study SERES-012 within 8 weeks of receipt of study drug will be eligible. The purpose of this cohort is to assess safety and efficacy of SER-109 in reducing recurrence of CDI in adults who had a CDI recurrence within 8 weeks after receipt of SER-109 or Placebo in study SERES-012. Cohort 2: Cohort 2 is an open-label program for subjects who were not part of SERES-012. The purpose of this cohort is to describe safety and tolerability of SER-109 in subjects 18 years of age or older with at least a first recurrence of CDI.
Detailed description
Cohort 1 is an open-label extension of study SERES-012. Subjects who had a CDI recurrence in study SERES-012 within 8 weeks of receipt of study drug, have responded to a course of standard of care (SOC) antibiotic treatment, will receive an oral dose of SER-109. A treatment regimen of SER-109 is defined as an oral dose of SER-109 (4 capsules once daily) for 3 consecutive days. Approximately 30 eligible subjects with recurrent CDI disease from study SERES-012 are expected to enroll. Screening for this study will begin at the Recurrence Visit of Study SERES-012. Cohort 2 is an open-label program for subjects who were not part of SERES-012. Subjects 18 years of age or older who had one or more CDI recurrence and have responded to a course of antibiotic treatment will receive an oral dose of SER-109. The CDI recurrence must be confirmed by a positive C. difficile stool toxin or polymerase chain reaction (PCR) assay to confirm eligibility. A treatment regimen of SER-109 is defined as an oral dose of SER-109 (4 capsules once daily) for 3 consecutive days. Approximately 200 eligible subjects with recurrent CDI disease are expected to enroll.
Interventions
BIOLOGICALSER-109
SER-109, an oral, biologically derived, live microbiome therapeutic that comprises purified bacterial spores
Sponsors
Seres Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Cohort 1 Main Inclusion Criteria: 1. Previously enrolled in Study SERES-012, had CDI recurrence within 8 weeks after receipt of a treatment regimen of SER-109 or placebo 2. 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. 3. The CDI recurrence in Study SERES-012 must have met the protocol definition of ≥ 3 unformed stools per day over 2 consecutive days, a positive C. difficile stool toxin assay, and the requirement of CDI SOC antibiotic therapy, and an adequate clinical response following antibiotic therapy (\<3 unformed stools in 24 hours for 2 or more consecutive days). Cohort 1 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/mm\^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) in the past 3 months. Cohort 2 Main Inclusion Criteria: 1. Subjects 18 years of age or older who had one or more CDI recurrence (as confirmed by a C. difficile stool toxin or PCR test) and have responded to a course of antibiotic treatment. 2. 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. Cohort 2 Main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1: Recurrence of CDI and Sustained Clinical Response | Up to Week 8 | Cohort 1: Recurrence of CDI up to 8 Weeks after treatment. Recurrence was determined by stool Clostridioides difficile toxin assay. Sustained clinical response was the absence of CDI recurrence up to 8 Weeks after treatment. |
| Cohort 2: Recurrence of CDI and Sustained Clinical Response | Up to Weeks 8 and 12 | Cohort 2: Recurrence of CDI up to 8 and 12 Weeks after treatment. Recurrence was determined by stool Clostridioides difficile toxin assay. Sustained clinical response was the absence of CDI recurrence up to 8 and 12 Weeks after treatment. |
Countries
Canada, United States
Participant flow
Recruitment details
Overall, there were 64 sites in the United States and 8 sites in Canada that enrolled participants between 2017 to 2021.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Rollover participants from study SERES-012, who received oral dose of SER-109 in 4 capsules once daily for 3 consecutive days in SERES-013 study. | 29 |
| Cohort 2 Newly enrolled participants who received oral dose of SER-109 in 4 capsules once daily for 3 consecutive days. | 234 |
| Total | 263 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 8 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Continuous | 71.7 years STANDARD_DEVIATION 12.46 | 63.1 years STANDARD_DEVIATION 15.79 | 64.0 years STANDARD_DEVIATION 15.67 |
| Antibiotic regimen for qualifying episode Fidaxomicin | 7 Participants | 65 Participants | 72 Participants |
| Antibiotic regimen for qualifying episode Vancomycin | 22 Participants | 169 Participants | 191 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 14 Participants | 14 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 20 Participants | 20 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 29 Participants | 214 Participants | 243 Participants |
| Race/Ethnicity, Customized White | 29 Participants | 214 Participants | 243 Participants |
| Sex: Female, Male Female | 18 Participants | 162 Participants | 180 Participants |
| Sex: Female, Male Male | 11 Participants | 72 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 8 / 234 |
| other Total, other adverse events | 14 / 29 | 68 / 234 |
| serious Total, serious adverse events | 1 / 29 | 32 / 234 |
Outcome results
Primary
Cohort 1: Recurrence of CDI and Sustained Clinical Response
Cohort 1: Recurrence of CDI up to 8 Weeks after treatment. Recurrence was determined by stool Clostridioides difficile toxin assay. Sustained clinical response was the absence of CDI recurrence up to 8 Weeks after treatment.
Time frame: Up to Week 8
Population: The analysis population consisted of all enrolled participants.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Cohort 1: Recurrence of CDI and Sustained Clinical Response | Number of participants with CDI recurrence | 4 Participants |
| Cohort 1 | Cohort 1: Recurrence of CDI and Sustained Clinical Response | Number of participants with sustained response | 25 Participants |
Primary
Cohort 2: Recurrence of CDI and Sustained Clinical Response
Cohort 2: Recurrence of CDI up to 8 and 12 Weeks after treatment. Recurrence was determined by stool Clostridioides difficile toxin assay. Sustained clinical response was the absence of CDI recurrence up to 8 and 12 Weeks after treatment.
Time frame: Up to Weeks 8 and 12
Population: The analysis population consisted of all enrolled participants.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Cohort 1 | Cohort 2: Recurrence of CDI and Sustained Clinical Response | Week 8 | Number of participants with CDI recurrence | 19 Participants |
| Cohort 1 | Cohort 2: Recurrence of CDI and Sustained Clinical Response | Week 8 | Number of participants with sustained clinical response | 215 Participants |
| Cohort 1 | Cohort 2: Recurrence of CDI and Sustained Clinical Response | Week 12 | Number of participants with CDI recurrence | 23 Participants |
| Cohort 1 | Cohort 2: Recurrence of CDI and Sustained Clinical Response | Week 12 | Number of participants with sustained clinical response | 211 Participants |