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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Men and Subjects With Ulcerative Colitis
• Intervention / Treatment: Drug: Placebo; Drug: KHK4083

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

"Part1:

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KHK4083; IV/SC administration	Drug: KHK4083
Placebo Comparator: Placebo; IV/SC administration	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): December 26, 2017
• Study Completion (Actual): December 26, 2017

Study Registration Dates

• First Submitted: November 28, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (Estimated): December 7, 2016

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Dermatologic Agents; KHK4083
• Other Study ID Numbers: 4083-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED