Study of a Monoclonal Antibody KHK4083 in Moderate Ulcerative Colitis

Exclusion Criteria

• •1. Subject, who, for any reason, is judged by the Investigator to be inappropriate for this study;
• •2. Subject has a medical history of other clinically significant diseases/disorders;
• •3. 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
• •4. Subject requires prescription treatment for UC, except for the stable, oral treatment of UC for 4 weeks prior to screening.
• •5. 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).
• •6. 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;
• •7. Subject with known colonic dysplasia, adenomas or polyposis;
• •8. Subject had major surgery within 4 weeks prior to Screening or an anticipated requirement for major surgery;
• •9. Subject with enteric pathogens (including Clostridium difficile);
• •10. Subject with any of the following hematological and chemistry laboratory values:
• •* Platelet count \< 100,000/mm3;
• •* Neutrophils \< 1500/mm3;
• •* Serum creatinine ≥ 1.6 mg/dL (≥ 144.4 μmol/L);
• •* Alkaline phosphatase \> 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%.
• •11. Subject has clinically significant cardiac disease;
• •12. Subject is pregnant or breastfeeding;
• •13. Subject has had major immunologic reaction;
• •14. Subject is Hepatitis B core antibody or surface antigen positive and/or Hepatitis C antibody positive with detectable RNA;
• •15. Subject has a history of human immunodeficiency virus (HIV) positivity, tests positive for HIV, or has congenital or acquired immunodeficiency;
• •16. 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 release assay \[IGRA\]) may be included in the study if prophylactic therapy for latent TB is started at least 4 weeks prior to Screening. Subjects with a potentially untreated other infection (clinical findings) are to be excluded.
• •17. Subject has bacterial infections requiring treatment with oral or parenteral antibiotics, within 2 and 4 weeks, respectively.
• •18. Subject has a history of systemic opportunistic infection or recurrent infections
• •19. Subject has malignancy or history of malignancy, except for adequately treated basal cell skin cancer or adequately treated carcinoma in-situ of the cervix without recurrence at least 5 years.
• •20. Subject who received a bacille Calmette-Guérin (BCG) vaccine within 6 months of randomization or live vaccination (e.g., measles, mumps, rubella \[MMR\]; herpes zoster; varicella, intranasal influenza; and oral poliomyelitis) within 4 weeks of randomization.
• •21. Subject with a history of or active substance abuse.
• •22. Subject has other severe acute or chronic medical or psychiatric condition or laboratory abnormality.