ECOSPOR IV: An Open-Label Extension of Study SERES-012 and Open-Label Program for Evaluating SER-109 in Subjects With Recurrent Clostridioides Difficile Infection (RCDI)
ECOSPOR IV: An Open-Label Extension of Study SERES-012 and Open-Label Program for Evaluating SER-109 in Subjects With Recurrent Clostridioides Difficile Infection (RCDI)
Cohort 1: Subjects who had a 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 Clostridioides difficile infection (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 within the past 12 months.
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, and who have completed their SERES-012 Week 8
 visit 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 Week 8 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 within 12 months and have responded
 to a course of SOC antibiotic treatment will receive an oral dose of SER-109. The CDI
 recurrence must be confirmed by a positive C. difficile stool toxin assay. A treatment
 regimen of SER-109 is defined as an oral dose of SER-109 (4 capsules once daily) for 3
 consecutive days.

 Approximately 195 eligible subjects with recurrent CDI disease are expected to enroll.
Cohort 1 Inclusion Criteria:

 1. Previously enrolled in Study SERES-012, had CDI recurrence within 8 weeks after
 receipt of study drug, and have completed their SERES-012 Week 8 visit.

 2. Signed informed consent prior to initiation of any study-specific procedure or
 treatment. The subject 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 test,
 and assessment by the investigator that the clinical condition of the subject
 warranted treatment.

 Cohort 1 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/ml3.

 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).

 Cohort 2 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 test) within 12 months and have responded to a course of
 standard of care antibiotic treatment.

 2. Signed informed consent prior to initiation of any study-specific procedure or
 treatment. The subject must be able to provide written informed consent and understand
 the potential risks and benefits from study enrollment and treatment.

 Cohort 2 Exclusion Criteria:

 (all Cohort 1 exclusion criteria [#1-8 above] plus the below addition criterion) 9.
 Previously enrolled in a Seres Therapeutics clinical study.