Clinical Trials

Inclusion Criteria: 

• Signed informed consent prior to initiation of any study-specific procedure or treatment. The subject must be willing to provide written informed consent and understand the potential risks and benefits from study enrollment and treatment. The subject must also be willing and able to comply with the scheduled visits, treatment plan, laboratory tests, daily eDiary and other study procedures.
• Male or female (non-lactating), 18-80 years of age, inclusive.
• Documented diagnosis of ulcerative colitis at least three (3) months prior to Screening, and with a minimum disease extent of 15 cm from the anal verge. Documentation should include lower endoscopic (flexible sigmoidoscopy or colonoscopy) evidence or histological evidence (biopsy report) of UC; however, UC medical treatment records may be sufficient, as determined by the PI. Subjects must also have a minimum disease extent of 15 cm from the anal verge, as determined at the Screening endoscopy.
• Active mild-to-moderate UC as determined by a Three-Component Modified Mayo Score of 3 to 7, inclusive, composed of endoscopic subscore (≥ 1, as determined by local and central reader scores, with adjudication by a second central reader, if necessary), stool frequency subscore (≥ 1) and rectal bleeding subscore (no eligibility requirement). There will be a maximum time of seven (7) business days between the Screening endoscopy and randomization.
• Subjects must be willing to undergo a lower endoscopy (flexible sigmoidoscopy or colonoscopy), including biopsy sample collection, at all specified timepoints.
• Subjects with an inadequate response to, loss of response to, or intolerance of, at least one (1) of the following conventional therapies: 5-ASA compounds, corticosteroids, 6-mercaptopurine (6-MP) or azathioprine (AZA), anti-TNFα, anti-integrin or tofacitinib.
• If female, is either:
  • Not of childbearing potential, defined as postmenopausal (≥ 12 continuous months of amenorrhea with no other cause than menopause) or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;
  • Of childbearing potential and participates in any activity associated with risk of pregnancy: is practicing at least one (1) highly effective method of birth control, including the barrier method, oral or parenteral contraceptives, a vasectomized partner or abstinence from sexual intercourse. The investigator will discuss with the subject the option of practicing more than one (1) of the above methods for the duration of the study.
• If male and partner is of childbearing potential, subject agrees to practice at least one (1) highly effective method of birth control for the duration of the study.

Note definition for Inclusion Criterion #6:

• Subjects who have demonstrated, over the previous five (5) year period, an inadequate response to, loss of response to, or intolerance of, at least one (1) of the following agents, as defined below:
  • 5-ASA compounds:
    • Signs and symptoms of persistently active disease despite taking a therapeutic dose of a 5-ASA compound (e.g., mesalamine ≥ 2.4 g/day or equivalent dose of another 5-ASA based on the product label for each compound, per PI judgement) for a minimum of four (4) weeks; or
    • History of intolerance to at least one (1) 5-ASA (discontinuation due to side effects).
  • Corticosteroids:
    • Signs and symptoms of persistently active disease despite a history of at least one (1) four-week induction regimen that included a dose equivalent to prednisone ≥ 30 mg or budesonide ≥ 9 mg daily, orally for at least two (2) weeks, or intravenously for at least one (1) week; or
    • Two (2) failed attempts to taper corticosteroids to below a dose equivalent to prednisone 10 mg daily, orally, on two (2) separate occasions; or
    • History of intolerance of corticosteroids (including, but not limited to Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia, or neuropsychiatric side-effects, including insomnia, associated with corticosteroid treatment).
  • Immunomodulators:
  • Signs and/or symptoms of persistently active disease despite at least three (3) months of treatment with one (1) of the following:
    • oral AZA (≥ 1.5 mg/kg/day) or 6-MP (≥ 0.75 mg/kg/day); or
    • oral AZA or 6-MP within a therapeutic range, as judged by thioguanine metabolite testing; or
    • a combination of a thiopurine and allopurinol within a therapeutic range, as judged by thioguanine metabolite testing; or
    • a history of intolerance to at least one (1) immunomodulator(including but not limited to nausea/vomiting, abdominal pain, pancreatitis, liver function test abnormalities and lymphopenia).
    • Pathway specific drugs for UC treatment, including anti-TNF antibodies, anti-integrin antibodies, or janus kinase (JAK) inhibitors (such as tofacitinib):
      • Signs and symptoms of persistently active disease despite induction treatment at the approved induction dosing that was indicated in the product label at the time of use; or
      • Loss of response: Recurrence of signs and symptoms of active disease during approved maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify as having failed or being intolerant to UC biologic therapy); or
      • Intolerance: History of intolerance to infliximab, adalimumab, golimumab, vedolizumab, tofacitinib or other approved biologics or JAK inhibitors (including but not limited to infusion-related event, demyelination, congestive heart failure, serious infection, or any other drug-related AE that led to a reduction in dose or discontinuation of the medication).

Exclusion Criteria: 

• Known history of Crohn’s disease.
• No previous history of treatment for UC (treatment-naïve subjects should not be enrolled).
• Subjects on steroid medication (e.g., prednisone, budesonide, budesonide MMX®) who are unable to have steroids tapered, and be completely off steroids at least two (2) weeks prior to Screening.
• Subjects who have received any investigational or approved biologic therapy (e.g., infliximab, adalimumab, golimumab, certolizumab, vedolizumab, ustekinumab, natalizumab) within eight (8) weeks prior to Screening or five (5) half-lives prior to Screening (whichever is longer).
• Subjects who have received any investigational or approved non-biologic therapy (e.g., cyclosporine, tacrolimus, thalidomide, methotrexate, tofacitinib), except for those specifically listed in the Permitted Concomitant Medications (e.g., stable dose of 6-mercaptopurine, azathioprine, methotrexate for ≥ 12 weeks prior to Screening), for the treatment of underlying disease, within 30 days or five (5) half-lives prior to Screening (whichever is longer).
• Major gastrointestinal surgery (not including appendectomy or cholecystectomy) within two (2) months before Screening, or any history of total colectomy.
• Subjects with active celiac disease (i.e., active diarrhea due to documented celiac disease).
• Subjects with evidence of, or treatment for, Clostridium difficile infection, or other intestinal pathogen, within 30 days prior to Screening.
• Subjects with Clostridium difficile positive stool, performed with a toxin enzyme immunoassay (EIA) by the Central Laboratory. Subjects who test positive for C. difficile can be treated with standard of care antibiotics and rescreened for the study after 30 days.
• Oral antibiotic use within 30 days before Screening.
• Expected to receive antibiotics (i.e., for planned/anticipated procedure) within the Induction Treatment period.
• Received an investigational drug or live vaccine within two (2) months before Screening.
• Previously enrolled in a Seres Therapeutics SER-109 or SER-287 study.
• Received a fecal microbiota transplant (FMT; includes human microbiota-based therapeutics) within three (3) months prior to Screening.
• Poor concurrent medical risks with clinically significant co-morbid disease such that, in the opinion of the investigator, the subject should not be enrolled including:
  • Known hypogammaglobulinemia;
  • Known severe immunodeficiency;
  • Underlying liver function test (LFT) [Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST)] abnormalities greater than 3x upper limit of normal (ULN);
  • Absolute neutrophil count (ANC) < 500 cells/mm^3;
  • Hemoglobin levels < 9 g/dL.
• Subjects with anatomic or medical contraindications to lower endoscopy (flexible sigmoidoscopy or colonoscopy), including but not necessarily limited to toxic megacolon, gastrointestinal 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 lower endoscopy (flexible sigmoidoscopy or colonoscopy).
• Unable to stop steroid enemas or suppositories, or 5-ASA enemas or suppositories, at least two (2) weeks prior to Screening.
• Unable to stop probiotic treatment at least one (1) week prior to Screening. Note: food containing probiotics are permitted.
• Known active malignancy, except for basal cell skin cancer or squamous cell skin cancer, or concurrent intensive induction chemotherapy, radiotherapy, or biologic treatment for active malignancy (subjects on maintenance chemotherapy may only be enrolled after consultation with medical monitor).
• Unable to comply with the protocol requirements, including the ability to take oral drugs; or any condition that, in the opinion of the investigator, might interfere with study objectives or compromise patient safety, including if the subject is likely to require surgery for UC during the study period.
• Known allergy or intolerance to oral vancomycin.
• Current or recent history (six [6] months prior to Screening) of drug or alcohol abuse.