A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC)

Main inclusion and exclusion criteria for the study Stage 1:

Subjects were eligible to be included in the study only if all the following criteria applied:

• Male or female subjects aged 18 to 75 years (inclusive) with a diagnosis of UC established at least 3 months prior to screening by clinical and endoscopic evidence corroborated by a histopathology report;
• Confirmed to have moderately to severely active UC within 14 days prior to the first dose of the investigational product, based on an adapted Mayo score of 4 to 9, and an endoscopic subscore of ≥2;
• Had evidence of UC extending to the rectum with ≥15 cm involvement on endoscopy;
• UC patients who were receiving treatment. Subjects could be enrolled if they met any items below:
• Prior to the randomization visit, subjects had received oral 5-aminosalicylic acid (5-ASA) (e.g., mesalazine, sulfasalazine, olsalazine, balsalazide) for at least 4 weeks with the dose stable for at least 2 weeks;
• Prior to the randomization visit, subjects had received oral or intravenous (IV) corticosteroids e.g. prednisone (daily doses ≤30 mg), budesonide (daily doses ≤9 mg), methylprednisolone (daily doses ≤24 mg), or equivalent dose of corticosteroids for at least 4 weeks, with the dose stable for at least 2 weeks;
• Oral 5-ASA or corticosteroid for treatment of UC had been stopped for at least 2 weeks prior to the screening endoscopy examination which was used for Mayo score assessment;
• A stable dosing regimen had to be used if non-prohibited concomitant medications were used.

Subjects who met any of the following criteria were excluded:

• Subjects had evidence of toxic megacolon;
• Had subtotal or total colectomy;
• An existing ileostomy, colostomy, or known symptomatic stenosis of the intestine; a history or evidence of adenomatous colonic polyps that had not been removed; a history or evidence of colonic mucosal dysplasia including low or high grade of dysplasia, as well as indeterminate for dysplasia; a suspected or confirmed diagnosis of Crohn's enterocolitis, undiagnosed types of colitis, ischemic colitis, or radiation colitis;
• Previous exposure to lymphocyte-depleting therapies or D-penicillamine, leflunomide; prior exposure to approved or investigational products that inhibited the lymphocyte trafficking;
• Received immunosuppressants within 30 days prior to randomization; received any investigational biologic or non-biologic agent, or approved biologic agent or biosimilars within 60 days or 5 half lives prior to screening (whichever was longer);
• Known active infection during the screening period; treatment for Clostridioides difficile (C. difficile) infection or other intestinal pathogen with 28 days prior to first dose of investigational product; active or latent tuberculosis (TB); Chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection; any identified congenital or acquired immunodeficiency;
• Received any live vaccine within 30 days prior to screening.

Main Inclusion and exclusion criteria for subjects' entry into the study Stage 2 from Stage 1:

Subjects who met all the following criteria entered into the study Stage 2:

• subjects with UC who completed 12 weeks of treatment with CBP-307 or placebo in Stage 1 and completed all the assessments (including colonoscopy) at study visit of Week 12 in study Stage 1;
• Good compliance in Stage 1;
• Subjects or their legal representatives voluntarily signed the ICF for study Stage 2.

Subjects who met any of the following criteria were excluded from the study Stage 2:

• subjects had any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, were to confound the study results or compromise subject safety;
• Allergic to CBP 307 or its excipients, experience of significant adverse events related to the study drug du