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

Phase 1

Completed

• Conditions: Healthy Men and Subjects With Ulcerative Colitis
• Interventions: Drug: KHK4083; Drug: Placebo

• Registration Number: NCT02985593
• Lead Sponsor: Kyowa Kirin Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-11-28
• Study Start: 2016-12
• Study First Submitted QC: 2016-12-05
• Study First Posted: 2016-12-07
• Primary Completion: 2017-12-26
• Study Completion: 2017-12-26
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-29
• Last Update Posted: 2023-08-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 155

Inclusion Criteria

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

Exclusion Criteria

1. Current illness requiring treatment;
2. Current respiratory, gastric, renal, or liver disease;

Part2:

Inclusion Criteria:

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

Exclusion Criteria:

1. 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;

2. 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);

3. 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);

4. 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;

5. Known colonic dysplasia, adenomas, or polyposis (excluding benign polyposis);

6. Any planned surgical treatment during the study;

7. Clostridium difficile infection within 8 weeks prior to enrollment;

8. 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;

9. Treatment with 5-aminosalicylic acid (5-ASA) enema, 5-ASA suppository, steroid enema, or steroid suppository within 2 weeks prior to enrollment;

10. Treatment with adalimumab within 2 weeks prior to enrollment or treatment with infliximab within 8 weeks prior to enrollment;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
KHK4083	KHK4083	IV/SC administration
Placebo	Placebo	IV/SC administration

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Area under the curve (AUC) 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
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
Anti-KHK4083 antibody production	art1: Up to 18 weeks post drug administration, Part2: Up to 22 weeks post drug administration