A Study Assessing the Efficacy and Safety of CBP-307 in Subjects With Moderate to Severe Ulcerative Colitis (UC)
Condition: Moderate to Severe Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: Double-Blind 0.2mg CBP-307; Double-Blind Placebo; Open-label CBP-307; Double-Blind 0.1mg CBP-307
Intervention description: 0.2 mg capsule oral administration; Placebo capsule oral administration; 0.2 mg capsule oral administration; 0.1 mg capsule oral administration
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 145.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This study will evaluate the efficacy and safety of CBP-307 in subjects with moderate to
      severe ulcerative colitis (UC).
    

Eligibility criteria:

        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:

               1. 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;

               2. 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 during Stage 1, and not appropriate to participate in Stage
             2 assessed by the investigator;

          -  Active or chronic recurrent infections;

          -  A history of uveitis or macular oedema.