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

Randomized, Double-blind, Phase 2 Study to Evaluate the Efficacy and the Safety of OSE-127 Versus Placebo in Subjects With Moderate to Severe Active Ulcerative Colitis Who Have Failed or Are Intolerant to Previous Treatment(s)

This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in patients with moderate to severe active ulcerative colitis.

Inclusion Criteria:

1. 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

2. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

3. Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks after last dose

4. Male or female 18 to 75 years of age, inclusive

5. 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:

   1. a rectal bleeding score ≥ 1,
   2. a stool frequency score ≥ 1 (sub-score calculated before bowel preparation), and
   3. an endoscopic sub-score ≥ 2

6. 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:

   1. Corticosteroids
   2. Immunosuppressive agents

OR

Previous or current biologic therapy

Exclusion Criteria:

1. Stoma, proctocolectomy, or subtotal colectomy

2. Physician judgment that patient is likely to require any surgery for UC during the study duration, or double-blind phase duration at least

3. Evidence of fulminant colitis, toxic megacolon, or perforation

4. Current or recent (within 4 weeks prior to screening) hospitalization for UC care and/or treatment with IV steroids

5. The following laboratory results at screening:

   1. 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
   2. Platelet count < 100,000/mm3
   3. Hemoglobin (Hgb) < 8.5 g/dL
   4. Neutrophils < 1500/mm3
   5. Lymphocytes < 800/mm3
   6. Absolute white blood cell (WBC) count < 3000/mm3

6. Crohn's disease or indeterminate colitis or any other diagnosis not consisting with UC

7. History or evidence of incompletely resected colonic dysplasia or unconventional lesion at risk of colonic adenocarcinoma

8. 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.

9. 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.

10. Breastfeeding

11. Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) from screening through the end of the study

12. 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)

13. 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)

14. 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)