A Study to Evaluate the Safety, Tolerability and Microbiome Dynamics of SER-287 in Subjects With Mild-to-Moderate Ulcerative Colitis

This is a Phase 1b multicenter, randomized, double-blind, placebo-controlled multiple dose study designed to evaluate the safety and tolerability of SER-287, and to evaluate the microbiome alterations and pharmacodynamics associated with two dosing regimens of SER-287 in adult subjects with active mild-to-moderate ulcerative colitis (UC).

Inclusion criteria

• Ulcerative colitis diagnosed by routine clinical, radiographic, endoscopic and pathologic criteria (preferably confirmed by colonoscopy and pathology records within last 2 years or if unavailable, will need approval by medical monitor) Active mild-moderate UC as determined by sigmoidoscopy within approximately 3 days of randomization to study

Exclusion criteria

• Fever > 38.3°C
• Known or suspected toxic megacolon and/or known small bowel ileus
• Known history of Crohn's disease
• Subjects with serum albumin <2.5 g/dL at baseline
• CMV polymerase chain reaction (PCR) positive from blood plasma at screening
• Known stool studies positive for ova and/or parasites or stool culture within the 30 days before enrollment
• Subjects on cyclosporine or triple immunosuppression, Triple immunosuppression will include any three of the following classes of drugs taken in combination: steroids (i.e., prednisone/budesonide/budesonide MMX), immunosuppressant (i.e., methotrexate/azathioprine/6-mercaptopurine), and/or other immunosuppressant (i.e., tacrolimus, cellcept).
• Biologic medication (infliximab/ adalimumab/ golimumab/ certolizumab/vedolizumab/ustekinumab/natalizumab) use within 3 months prior to screening
• Known active malignancy except for basal cell skin cancer, squamous cell skin cancer
• Subjects with previous colectomy, ostomy, J-pouch, or previous intestinal surgery (excluding cholecystectomy, appendectomy)
• Subjects with known history of celiac disease or gluten enteropathy
• Subjects with Clostridium difficile positive stool at Screening Visit
• Antibiotic use within the prior 1 month before randomization
• Expected to receive antibiotics within 8 weeks of signing the Informed Consent Form (ICF) (i.e., for planned/anticipated procedure)
• Received an investigational drug within 1 month before study entry
• Received an investigational antibody or vaccine within 3 months before study entry
• Previously enrolled in a SER-109/SER-287 study
• Received an FMT within the last 6 months
• Subjects with anatomic or medical contraindications to flexible sigmoidoscopy, including but not necessarily limited to toxic megacolon, gastrointestinal (GI) fistulas, immediate post-operative status from abdominal surgery, severe coagulopathy, large or symptomatic abdominal aortic aneurysm, or any subject where study physician deems subject at significant risk of complications of flexible sigmoidoscopy
• Unable to stop steroid enemas or suppositories or mesalamine enemas or suppositories before screening visit
• Unable to stop opiate treatment unless on a stable dose and no increase in dose planned for the duration of the study
• Unable to stop probiotics before screening visit
• Concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy (subjects on maintenance chemotherapy may only be enrolled after consultation with medical monitor)
• Known allergy or intolerance to oral vancomycin

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