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

Study Overview
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Brief Summary
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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.

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

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: KHK4323 IV/S
* Drug: KHK4323 SC/S
* Drug: KHK4323 IV/M
* Drug: Placebo IV/S
* Drug: Placebo IV/M
* Drug: Placebo SC/S


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part1 Dose 1A<br>Single administration | Drug: KHK4323 IV/S<br>* IV / Single administration<br>|
| Placebo Comparator: Part1 Dose 1P<br>Single administration | Drug: Placebo IV/S<br>* IV / Single administration<br>|
| Experimental: Part1 Dose 2A<br>Single administration | Drug: KHK4323 IV/S<br>* IV / Single administration<br>|
| Placebo Comparator: Part1 Dose 2P<br>Single administration | Drug: Placebo IV/S<br>* IV / Single administration<br>|
| Experimental: Part1 Dose 3A<br>Single administration | Drug: KHK4323 IV/S<br>* IV / Single administration<br>|
| Placebo Comparator: Part1 Dose 3P<br>Single administration | Drug: Placebo IV/S<br>* IV / Single administration<br>|
| Experimental: Part1 Dose 4A<br>Single administration | Drug: KHK4323 IV/S<br>* IV / Single administration<br>|
| Placebo Comparator: Part1 Dose 4P<br>Single administration | Drug: Placebo IV/S<br>* IV / Single administration<br>|
| Experimental: Part1 Dose 5A<br>Single administration | Drug: KHK4323 SC/S<br>* SC / Single administration<br>|
| Placebo Comparator: Part1 Dose 5P<br>Single administration | Drug: Placebo SC/S<br>* SC / Single administration<br>|
| Experimental: Part1 Dose 6A<br>Single administration | Drug: KHK4323 IV/S<br>* IV / Single administration<br>|
| Placebo Comparator: Part1 Dose 6P<br>Single administration | Drug: Placebo IV/S<br>* IV / Single administration<br>|
| Experimental: Part1 Dose 7A<br>Single administration | Drug: KHK4323 IV/S<br>* IV / Single administration<br>|
| Placebo Comparator: Part1 Dose 7P<br>Single administration | Drug: Placebo IV/S<br>* IV / Single administration<br>|
| Experimental: Part2 Dose 1A<br>Multiple administration | Drug: KHK4323 IV/M<br>* IV / Multiple administration<br>|
| Placebo Comparator: Part2 Dose 1P<br>Multiple administration | Drug: Placebo IV/M<br>* IV / Multiple administration<br>|
| Experimental: Part2 Dose 2A<br>Multiple administration | Drug: KHK4323 IV/M<br>* IV / Multiple administration<br>|
| Placebo Comparator: Part2 Dose 2P<br>Multiple administration | Drug: Placebo IV/M<br>* IV / Multiple administration<br>|

What is the study measuring?
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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 |