Study of OSE-127 vs Placebo in Patients With Moderate to Severe Active Ulcerative Colitis

Inclusion criteria

• Provision of signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose
• Male or female 18 to 75 years of age, inclusive
• Diagnosis of moderate to severe active UC made at least 3 months before the screening visit. The diagnosis of UC must have been confirmed by endoscopy, with a minimal extent of 15 cm from anal margin and histology (Moderate to severe active UC is defined by a modified Mayo score between 4 and 9, inclusive. The modified Mayo score is defined by the addition of the rectal bleeding subscore, the stool frequency sub-score, and the endoscopic sub-score. Thus, to be included, a patient must have the following:

• a rectal bleeding score ≥ 1,
• a stool frequency score ≥ 1 (sub-score calculated before bowel preparation), and
• an endoscopic sub-score ≥ 2
• No previous biologic therapy (i.e., TNF antagonists, vedolizumab or ustekinumab) and prior or current UC documented medication history that includes at least 1 of the following:

• Corticosteroids
• Immunosuppressive agents

OR

Previous or current biologic therapy

Exclusion criteria

• Stoma, proctocolectomy, or subtotal colectomy
• Physician judgment that patient is likely to require any surgery for UC during the study duration, or double-blind phase duration at least
• Evidence of fulminant colitis, toxic megacolon, or perforation
• Current or recent (within 4 weeks prior to screening) hospitalization for UC care and/or treatment with IV steroids
• The following laboratory results at screening:

• Elevation at screening of aminotransferase (AST), alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) or total bilirubin > 2 × ULN (unless due to Gilbert's disease) or evidence of chronic liver disease
• Platelet count < 100,000/mm3
• Hemoglobin (Hgb) < 8.5 g/dL
• Neutrophils < 1500/mm3
• Lymphocytes < 800/mm3
• Absolute white blood cell (WBC) count < 3000/mm3
• Crohn's disease or indeterminate colitis or any other diagnosis not consisting with UC
• History or evidence of incompletely resected colonic dysplasia or unconventional lesion at risk of colonic adenocarcinoma
• Stool culture or other examination positive for enteric pathogen, including Clostridium difficile (C. diff) toxin. If positive, the patient should be treated and rescreening is allowed.
• Men or women with childbearing potential not willing to use adequate birth control during the study. Adequate birth control includes surgical sterilization, intrauterine device, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy, double-barrier method (condom, diaphragm with spermicide), or abstinence during study and 30 days following the last follow-up visit. Women of childbearing potential will enter the study after a negative pregnancy test.
• Breastfeeding
• Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) from screening through the end of the study
• Use of topical steroids and/or topical 5-aminosalicylic acid preparations within 2 weeks before the screening visit (all such medications should be withdrawn at least 2 weeks prior to the screening visit)
• Use of antidiarrheals within 2 weeks before the screening visit (all such medications should be withdrawn at least 2 weeks prior to the screening visit)
• Treatment with azathioprine, 6-MP, methotrexate (MTX), cyclosporin, tacrolimus, sirolimus, leflunomide and/or mycophenolate mofetil within 4 weeks before the screening visit (all such medications should be withdrawn at least 4 weeks prior to the screening visit)