Study of KHK 4323 in Healthy Volunteers and Subjects With Atopic Dermatitis

A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Single Dose or Multiple Dose Study of KHK4323 in Healthy Volunteers, and Subjects With Atopic Dermatitis

Part 1: To investigate the safety and tolerability of intravenous (IV) or subcutaneous (SC) administration of a single dose of KHK4323 to Japanese or Caucasian healthy adult males in a double-blind, placebo-controlled study.

Part 2: To investigate the safety and tolerability of intravenous (IV) administration of repeated doses of KHK4323 to atopic dermatitis patients in a double-blind, placebo-controlled study.

Study Overview

• Status: Terminated
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: KHK4323 IV/S; Drug: Placebo IV/S; Drug: KHK4323 SC/S; Drug: Placebo SC/S; Drug: KHK4323 IV/M; Drug: Placebo IV/M

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan
    • Osaka Pharmacology Clinical Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Part 1:

• Japanese or Caucasian male aged 20 to under 45 years old at the time consent was obtained
• BMI ≥ 18.5 to < 30.0 at time of screening tests

Part 2:

• Men and women aged 18 years or older at the time of consent
• Patients with EASI ≥ 16 in pre-administration testing
• Patients with IGA of "3: Moderate" or higher in pre-administration testing
• Patients with BSA ≥ 10% at screening in pre-administration testing

"Exclusion Criteria:

Part 1:

• Persons with existing respiratory disease, heart disease, gastrointestinal disease, kidney disease, or liver disease
• Persons confirmed to have a bacterial, viral, fungal, or parasitic infection within 28 days prior to obtainment of consent
• Persons who have contracted an infectious disease requiring hospitalization or IV administration of an antibiotic within 6 months prior to obtainment of consent
• Persons who have been treated with a biological preparation (antibody, etc.) or have been administered an investigational drug within 6 months prior to the obtainment of consent
• Persons who have used a medication (including over-the-counter drugs, topical agents, vitamins, and herbal medicines) within 2 weeks prior to obtainment of consent (for an immunosuppressant drug, within 60 days)
• Persons who routinely smoke an average of more than 10 cigarettes a day (to be confirmed in interview at time of screening tests) or cannot follow the rules regarding smoking during the clinical trial period

Part 2:

• Patients with severe complications judged to affect the implementation and evaluation of the study in the opinion of the investigator or sub-investigator. Includes but is not limited to the following. Severe cardiovascular disease (e.g., class III or IV according to New York Heart Association functional classification), poorly controlled diabetes mellitus (HbA1c > 8.5%), poorly controlled hypertension, liver disease with severity of moderate or higher (e.g., class B or C according to Child-Pugh classification), kidney disease, respiratory disease, gastrointestinal disease, blood dyscrasia, central nervous system disease, psychiatric disease, autoimmune disease, etc.

• Patients observed to have one of the following laboratory test abnormalities in screening tests

  • Neutrophil count: < 1500/μL
  • Serum creatinine: > 1.5 mg/dL
  • AST or ALT: > 2.5-fold the upper limit of the reference range
  • Other laboratory test abnormalities that the investigator or sub-investigator thinks could affect the completion or evaluation of the clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

18

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part1 Dose 1A; Single administration	Drug: KHK4323 IV/S; IV / Single administration
PLACEBO_COMPARATOR: Part1 Dose 1P; Single administration	Drug: Placebo IV/S; IV / Single administration
EXPERIMENTAL: Part1 Dose 2A; Single administration	Drug: KHK4323 IV/S; IV / Single administration
PLACEBO_COMPARATOR: Part1 Dose 2P; Single administration	Drug: Placebo IV/S; IV / Single administration
EXPERIMENTAL: Part1 Dose 3A; Single administration	Drug: KHK4323 IV/S; IV / Single administration
PLACEBO_COMPARATOR: Part1 Dose 3P; Single administration	Drug: Placebo IV/S; IV / Single administration
EXPERIMENTAL: Part1 Dose 4A; Single administration	Drug: KHK4323 IV/S; IV / Single administration
PLACEBO_COMPARATOR: Part1 Dose 4P; Single administration	Drug: Placebo IV/S; IV / Single administration
EXPERIMENTAL: Part1 Dose 5A; Single administration	Drug: KHK4323 SC/S; SC / Single administration
PLACEBO_COMPARATOR: Part1 Dose 5P; Single administration	Drug: Placebo SC/S; SC / Single administration
EXPERIMENTAL: Part1 Dose 6A; Single administration	Drug: KHK4323 IV/S; IV / Single administration
PLACEBO_COMPARATOR: Part1 Dose 6P; Single administration	Drug: Placebo IV/S; IV / Single administration
EXPERIMENTAL: Part1 Dose 7A; Single administration	Drug: KHK4323 IV/S; IV / Single administration
PLACEBO_COMPARATOR: Part1 Dose 7P; Single administration	Drug: Placebo IV/S; IV / Single administration
EXPERIMENTAL: Part2 Dose 1A; Multiple administration	Drug: KHK4323 IV/M; IV / Multiple administration
PLACEBO_COMPARATOR: Part2 Dose 1P; Multiple administration	Drug: Placebo IV/M; IV / Multiple administration
EXPERIMENTAL: Part2 Dose 2A; Multiple administration	Drug: KHK4323 IV/M; IV / Multiple administration
PLACEBO_COMPARATOR: Part2 Dose 2P; Multiple administration	Drug: Placebo IV/M; IV / Multiple administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	For adverse events that occurred after administration of the investigational drug, number of subjects with AEs and occurrence frequency are classified by MedDRA PT and SOC and shown according to dose group.	Part 1: from Day 1 through at most Day 169, Part 2: from Day 1 through at most Day 225

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Profile of pharmacokinetics of serum KHK4323 concentration in Part 1	Anti-KHK4323 antibodies	Day 1 (pre-dose, 1, 6 hours after the start of administration) Day 2, Day 3, Day 4, Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141, Day 169
Profile of pharmacokinetics of serum KHK4323 concentration in Part 2	Anti-KHK4323 antibodies	Day 1( pre-dose, 1 hours after the start of administration), Day 8, Day 15, Day 29,Day 43, Day 57, Day 85, Day 113, Day 169, Day 225

Other Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Eczema Area and Severity Index (EASI)	Part2: Day1(Pre-dose), Day 15, Day 29,Day 43, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225
Percent change in Eczema Area and Severity Index (EASI)	Part2: Day1(Pre-dose), Day 15, Day 29,Day 43, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225
Change from baseline in Body surface area (BSA) of involvement of Atopic dermatitis	Part2 Day1(Pre-dose), Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225
Percent change in Body surface area (BSA) of involvement of Atopic dermatitis	Part2 Day1(Pre-dose), Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225
The number of subjects with IGA of 0 or 1 and improvement of 2 points or more over baseline score (IGA responders)	Part2 Day1(Pre-dose), Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225
The percentage of subjects with IGA of 0 or 1 and improvement of 2 points or more over baseline score (IGA responders)	Part2 Day1(Pre-dose), Day 15, Day 29, Day 43, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 22, 2019
• Primary Completion (ACTUAL): December 11, 2019
• Study Completion (ACTUAL): December 11, 2019

Study Registration Dates

• First Submitted: February 17, 2019
• First Submitted That Met QC Criteria: February 17, 2019
• First Posted (ACTUAL): February 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 28, 2020
• Last Update Submitted That Met QC Criteria: January 26, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: 4323-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No