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

Study Overview
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Brief Summary
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The objectives of this study are to evaluate the safety and tolerability of a single intravenous (IV) or subcutaneous (SC) dose of KHK4083 in Japanese or White healthy men in a placebo-controlled, single-blind comparative study, and to evaluate the safety and tolerability of multiple IV doses of KHK4083 in subjects with ulcerative colitis in an open-label study.

Official Title
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A Phase 1, Single-Blind, Randomized, Placebo-Controlled, Single-Dose or Open-Label Multiple-Dose Study of KHK4083 in Healthy Adults and Subjects With Ulcerative Colitis

Conditions
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Healthy Men and Subjects With Ulcerative Colitis

Intervention / Treatment
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* Drug: KHK4083
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KHK4083<br>IV/SC administration | Drug: KHK4083<br> <br> |
| Placebo Comparator: Placebo<br>IV/SC administration | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) or drug-related TEAEs and their nature |  | Part1: Up to 18 weeks post drug administration, Part2: Up to 22 weeks post drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum KHK4083 concentration |  | Part1: Up to 18 weeks post drug administration, Part2: Up to 22 weeks post drug administration | 
| Maximum concentration (Cmax) of KHK4083 |  | Part1: Up to 18 weeks post drug administration, Part2: Up to 22 weeks post drug administration | 
| Time to reach Cmax (tmax) of KHK4083 |  | Part1: Up to 18 weeks post drug administration, Part2: Up to 22 weeks post drug administration | 
| Area under the curve (AUC) of KHK4083 |  | Part1: Up to 18 weeks post drug administration, Part2: Up to 22 weeks post drug administration | 
| Anti-KHK4083 antibody production |  | art1: Up to 18 weeks post drug administration, Part2: Up to 22 weeks post drug administration |