A Phase 1 Study of KHK4083 in Healthy Volunteers and Subjects With Ulcerative Colitis

"Part1:

Inclusion criteria

• Voluntary written informed consent to participate in the study;
• Japanese or White men ≥20 and <45 years at the time of informed consent;

Exclusion criteria

• Current illness requiring treatment;
• Current respiratory, gastric, renal, or liver disease;

Part2:

Inclusion criteria

• Voluntary written informed consent to participate in the study;
• Men or women ≥20 years of age at the time of informed consent;
• Ulcerative colitis diagnosed ≥6 months prior to informed consent;
• Moderate or more severe ulcerative colitis;

Exclusion criteria

• Definitive diagnosis of bacillary dysentery, amebic colitis, Salmonella enteritis, Campylobacter enteritis, colonic tuberculosis, Chlamydia enteritis, Crohn's disease, radiation colitis, drug-induced colitis, angiolymphoid hyperplasia, ischemic colitis, or intestinal Behcet's disease;
• Any of the following clinically significant concurrent illnesses:

• Type 1 diabetes
• Poorly controlled type 2 diabetes (HbA1c >8.5%)
• Congestive heart failure (class II to IV of the New York Heart Association classification)
• Myocardial infarction within 1 year
• Unstable angina pectoris within 1 year
• Poorly controlled hypertension (systolic pressure >150 mmHg or diastolic pressure >90 mmHg at screening)
• Severe chronic lung diseases requiring oxygen therapy
• Multiple sclerosis or other demyelinating diseases
• Active malignancies, or onset or a history of treatment of malignancies within 5 years prior to informed consent (except for resected or surgically cured epithelial carcinoma of the uterine cervix, cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, or ductal carcinoma);
• Current or past history of clinically significant cardiovascular, liver, renal, respiratory, hematologic, central nervous system, psychiatric, or autoimmune diseases/disorders other than those in 2);
• Suspected or confirmed symptomatic stenosis of the colon, abdominal abscess, or ischemic colitis based on clinical or radiographic data within 1 year prior to enrollment; suspected or confirmed toxic megacolon or history of toxic megacolon; history of any colonic resection, subtotal or total colectomy, ileostomy, or colostomy; or any previous surgery for ulcerative colitis or an anticipated requirement for surgery for ulcerative colitis;
• Known colonic dysplasia, adenomas, or polyposis (excluding benign polyposis);
• Any planned surgical treatment during the study;
• Clostridium difficile infection within 8 weeks prior to enrollment;
• Any active infection, including Grade ≥2 localized diseases per Common Terminology Criteria for Adverse Events, version 4.0, Japan Clinical Oncology Group edition (CTCAE v4.0-JCOG), within 4 weeks prior to enrollment;
• Treatment with 5-aminosalicylic acid (5-ASA) enema, 5-ASA suppository, steroid enema, or steroid suppository within 2 weeks prior to enrollment;
• Treatment with adalimumab within 2 weeks prior to enrollment or treatment with infliximab within 8 weeks prior to enrollment;