Study of a Monoclonal Antibody KHK4083 in Moderate Ulcerative Colitis

This is an interventional treatment trial for Ulcerative Colitis focused on measuring 4083-002, Intestinal Diseases, Ulcerative Colitis, UC, Mayo Clinic Scoring, Gastrointestinal Tract Read More

Inclusion Criteria:

1. 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;
2. Subject voluntarily signs/dates an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF in accordance with regulatory and Institutional Guidelines;
3. Male and female subjects ≥ 18 years of age at the time of enrollment;
4. Subject has UC that was diagnosed at least 6 months prior to the Screening visit;
5. 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;
6. 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.
7. Female subjects (WOCBP) must have a negative pregnancy test at Screening and Baseline. WOCBP must agree to use effective contraception;
8. 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:

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.