Study of a Monoclonal Antibody KHK4083 in Moderate Ulcerative Colitis

Inclusion Criteria

• Subject is able and willing to comply with study procedures, and to adhere to dosing, visit schedules and follow-up procedures as described in the protocol and ICF;
• Subject voluntarily signs/dates an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF in accordance with regulatory and Institutional Guidelines;
• Male and female subjects ≥ 18 years of age at the time of enrollment;
• Subject has UC that was diagnosed at least 6 months prior to the Screening visit;
• Subject has moderately active UC with a total Mayo score of 4-9 and an endoscopic sub-score of at least 2, with disease that extends at least 15 cm from the anal verge;
• Subject has had previous treatment (within 5 years prior to Screening) with one or more of the following: corticosteroids, immunosuppressive medications or TNF antagonist therapy that was unsuccessful because of a lack of efficacy response.
• Female subjects (WOCBP) must have a negative pregnancy test at Screening and Baseline. WOCBP must agree to use effective contraception;
• Male subjects (including those who have had a vasectomy) must use adequate contraception during the study and for at least 6 months after the last dose of investigational product.

Exclusion Criteria

• Subject, who, for any reason, is judged by the Investigator to be inappropriate for this study;
• Subject has a medical history of other clinically significant diseases/disorders;
• Two or more biologic treatments with different mechanisms of action (e.g., infliximab, vedolizumab and golimumab) or Three or more anti-TNF biologics e.g. infliximab, adalimumab
• Subject requires prescription treatment for UC, except for the stable, oral treatment of UC for 4 weeks prior to screening.
• Subject has received any of the following prior treatments or treatments within the specified time prior to the Baseline visit:
• Natalizumab, efalizumab, rituximab or other lymphocyte-depleting treatments, including but not limited, to alkylating agents (such as cyclophosphamide or chlorambucil) and total lymphoid irradiation at any time;
• TNF antagonists within 8 weeks, or 5 half-lives (up to 12 weeks);
• Vedolizumab within 16 weeks;
• Methotrexate, cyclosporine, mycophenolate, tacrolimus, thalidomide, or other immune altering drugs within 4 weeks (ophthalmologic preparations are permitted);
• 5-ASA enema, steroid enema or suppository use within 2 weeks ; and/or Investigational agents within 8 weeks or 5 half-lives (whichever is longer).
• Subject with recent, suspected or confirmed symptomatic stenosis of the colon, abdominal abscess, or ischemic colitis based on clinical or radiographic data; a history of toxic megacolon; or who had any previous surgery for UC;
• Subject with known colonic dysplasia, adenomas or polyposis;
• Subject had major surgery within 4 weeks prior to Screening or an anticipated requirement for major surgery;
• Subject with enteric pathogens (including Clostridium difficile);
• Subject with any of the following hematological and chemistry laboratory values:
• Platelet count 3 times the upper limit of normal (ULN);
• AST or ALT > 2 times ULN;
• Total bilirubin > 2 mg/dL, unless due to Gilbert's Syndrome;
• Serum albumin < 3 g/dL;
• Hemoglobin < 9 g/dL;
• Glycated serum hemoglobin A1c ≥ 9%.
• Subject has clinically significant cardiac disease;
• Subject is pregnant or breastfeeding;
• Subject has had major immunologic reaction;
• Subject is Hepatitis B core antibody or surface antigen positive and/or Hepatitis C antibody positive with detectable RNA;
• Subject has a history of human immunodeficiency virus (HIV) positivity, tests positive for HIV, or has congenital or acquired immunodeficiency;
• Subject has or has had active TB, suspected extra-pulmonary TB, a history of incompletely treated TB, or latent TB or other latent infection. Subjects with latent TB (clinical findings, purified protein derivative [PPD] or interferon gamma rele