Ensayos clínicos

Inclusion Criteria:

• Signed informed consent.
• Men or women, 18 to 70 years of age.
• Established diagnosis of UC for at least 3 months prior to screening, based on clinical history, exclusion of infectious causes, and characteristic endoscopic and histologic findings.
• Active UC with disease involving the colon and rectum, with at least 15 cm of involved colon; subjects with isolated ulcerative proctitis (disease that does not extend beyond 15 cm of the anal verge) will be excluded.
• Modified Mayo Score 3-6, with a score of ≤ 2 points in any individual category of the modified Mayo scoring system and endoscopy score activity of at least 1 point at the most affected area, based on a flexible sigmoidoscopy done within 21 days of the baseline visit (V1). For subjects who have not undergone full colonoscopy within the past 24-months, a full colonoscopy will be performed in lieu of flexible sigmoidoscopy. Only the sigmoid should be scored up to approximately 30-40 cm, although the extent of disease beyond this level will be documented for subjects receiving full colonoscopy or sigmoidoscopy.
• Subjects with active disease (defined per clinical and endoscopy criteria) despite ongoing treatment with oral mesalamine ≥ 2.4 g/day with or without concomitant topical (rectal) mesalamine (mesalamine suppository 1000mg PR QHS or mesalamine enema 4g PR QHS) for ≥ 4 weeks from screening visit.
• Treatment with stable dosage of oral mesalamine and concomitant topical (rectal) mesalamine (if applicable) during study screening and treatment phases.
• Treatment with a stable oral corticosteroid dose of ≤ 15 mg prednisone/day or equivalent during study screening and treatment phase.
• Negative pregnancy test in females of childbearing potential at time of randomization.
• All fertile male and female subjects must agree to use a reliable method of contraception for duration of the trial. These include intrauterine device, implantable progesterone device, progesterone intramuscular injection, oral contraceptive initiated at least one month prior to visit one and continuing for duration of the trial, contraceptive patch, condom with spermicide, or abstinence from sexual intercourse.
• Willing and able to meet all study requirements, including attending all assessment visits, submitting for endoscopy with biopsy sampling at screening and End-of-Treatment/Early Termination visits.
• Must be able to respond to telephone follow-up calls.

Exclusion Criteria:

• Enrollment into Cohort A will serve as non-eligibility criterion for enrollment into Cohort B; i.e., the two cohorts will enroll eligible, non-overlapping subjects.
• Diagnostic uncertainty in the opinion of the Principal Investigator with possibility of Crohn's disease, presence or history of a fistula consistent with Crohn's Disease, indeterminate colitis, ischemic colitis, radiation colitis, microscopic colitis (i.e., collagenous colitis and lymphocytic colitis), diverticular-disease-associated colitis, infectious colitis, celiac disease, actively bleeding hemorrhoids, other inflammatory or bleeding disorders of the colon and intestine, or disease that may cause diarrhea or gastrointestinal bleeding.
• Current or prior diagnosis of toxic megacolon or fulminant colitis.
• History of prior gastrointestinal tract stricture and/or prior surgical intervention in any region of the gastrointestinal tract (excluding minor surgery; for example hemorrhoidectomy or uncomplicated appendectomy).
• Prior diagnosis of cardiovascular, renal, hepatic, endocrine, infectious, hematological, neuro-psychiatric disease or immune-mediated inflammatory disease, which in the opinion of the Principal Investigator might impact the subject’s safety or compliance, or the interpretation of results.
• Prior history of, or presence of, prolonged QTc during screening (>450 ms in men and > 470 ms in women).
• Any immunosuppressive condition or treatment with immunosuppressive medications other than those indicated for the treatment of UC. This includes immune deficiency associated with, but not limited to, advanced HIV/AIDS, bone marrow or solid organ transplant .
• History of cancer in the last three years; curatively treated superficial non-metastatic cancers are permitted.
• Hemoglobin concentration < 9 g/dL, WBC below 3,000/cm3 or platelets below 100,000/cm3.
• Chronic kidney disease with an estimated glomerular filtration rate of <30 mL/min calculated by modification of diet in renal disease (MDRD) equation at screening (Levey and Uhlig, 2006).
• Abnormal hepatic function (ALT or AP > 2.5x ULN at screening visit, or documented liver cirrhosis).
• C. difficile infection ≤ 3 months prior to baseline visit.
• Detection of a gastrointestinal pathogen on stool analysis at the time of screening evaluation or CMV detection in biopsy tissue from screening endoscopy (prior infection is not an exclusion to enrollment as long as successful treatment and eradication are documented).
• Prior history of fecal microbiota transplantation (FMT) or treatment with a live biotherapeutic product ≤ 6 months prior to baseline visit.
• Use of any over-the-counter non-food category probiotic agent ≤ 2 weeks prior to baseline visit and during study duration.
• Use of proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs) ≤ 2 weeks prior to baseline visit and during study duration.
• Diagnosis of malabsorption syndrome(s) that may interfere with clinical disease assessment.
• Diagnosis of primary sclerosing cholangitis (PSC) or bile acid malabsorption.
• Treatment with systemic antibiotics ≤ 4 weeks prior to baseline visit and during study duration.
• Treatment with oral corticosteroids at daily dose of >15 mg of prednisone or equivalent ≤2 weeks prior to screening visit.
• Treatment with topical (rectal) corticosteroids; e.g., budesonide ≤2 weeks prior to screening visit.
• Treatment with intravenous or intramuscular corticosteroids ≤4 weeks prior to screening visit.
• Ongoing treatment or failed prior treatment with methotrexate, azathioprine, 6-mercaptopurine, cyclosporine, tofacitinib, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus (FK-506), or biologics (e.g., TNF-alpha-antagonists, anti-integrin therapies, agents targeting IL-12 or IL-23, etc.).
• Known intolerance/allergic reaction to imipenem or metronidazole, that may be used to treat infections potentially acquired from ABI-M201 bacterial strains.
• Concomitant treatment with coumarins (e.g., warfarin, phenprocoumon).
• Treatment with any other investigational drugs ≤ 12 weeks prior to baseline visit.
• Clinical suspicion or history of abuse/addiction to alcohol or drugs, including opiates.
• Existing or intended pregnancy or breast-feeding during study duration.
• Subjects deemed by the Principal Investigator to be unlikely to comply with protocol requirements, instructions and study-related restrictions, or successfully complete the study; e.g., uncooperative attitude, inability to return for follow-up visits etc.
• The participant has a condition or is in a situation which, in the Principal Investigator’s opinion, may put the participant at significant risk, may confound the study results, or may interfere significantly with the participant’s participation in the study.
• Participant is directly or indirectly involved in the conduct and administration of this study as a Principal Investigator, sub-investigator, study coordinator, other study staff member, or employees of Allergan, Inc. or Assembly Biosciences; or the participant is a first-degree family member, significant other, or relative residing with one of the above persons involved directly or indirectly in the study; or the participant is enrolled in this study at another clinical study site.
• Out of range exclusionary laboratory values may be recollected a single time only if determined to be spurious by the Principal Investigator when results are reported, or initial results are not believed to be reflective of the subjects’ usual state, e.g. elevated blood urea nitrogen (BUN)/Creatinine (Cr) possibly due to dehydration. In subjects with evidence of UC complicated by infectious colitis (e.g., pathogenic bacteria or Clostridium difficile infection) at screening, those subjects may be rescreened with clinical evidence (i.e., negative culture) of eradication of pathogenic organisms.