Study of an Anti-OX40 Monoclonal Antibody (KHK4083) in Subjects With Moderate to Severe Atopic Dermatitis

A Phase 2, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of an Anti-OX40 Monoclonal Antibody (KHK4083) in Subjects With Moderate to Severe Atopic Dermatitis (AD)

A Phase 2, multicenter, randomized, placebo-controlled, double-blind, parallel-group study for subjects with moderate to severe AD whose disease cannot be adequately controlled with topical medications or for whom topical treatment is medically inadvisable.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Placebo; Drug: KHK4083

• Study Type: Interventional
• Enrollment (Actual): 274
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Markham, Ontario, Canada
      • Kyowa Investigational Site CA-02
    • Richmond Hill, Ontario, Canada
      • Kyowa Investigational Site CA-03
    • Richmond Hill, Ontario, Canada
      • Kyowa Investigational Site CA-08
  • Quebec
    • Quebec City, Quebec, Canada
      • Kyowa Investigational Site CA-07
    • Quebec City, Quebec, Canada
      • Kyowa Investigational Site CA-09
    • Sherbrooke, Quebec, Canada
      • Kyowa Investigational Site CA-04
• Germany
  • Aachen, Germany
    • Kyowa Investigational Site GE-13
  • Berlin, Germany
    • Kyowa Investigational Site GE-07
  • Berlin, Germany
    • Kyowa Investigational Site GE-14
  • Darmstadt, Germany
    • Kyowa Investigational Site GE-08
  • Frankfurt am Main, Germany
    • Kyowa Investigational Site GE-05
  • Hamburg, Germany
    • Kyowa Investigational Site GE-02
  • Hannover, Germany
    • Kyowa Investigational Site GE-11
  • Langenau, Germany
    • Kyowa Investigational Site GE-01
• Japan
  • Aichi, Japan
    • Kyowa Investigational Site JP-17
  • Aichi, Japan
    • Kyowa Investigational Site JP-27
  • Chiba, Japan
    • Kyowa Investigational Site JP-24
  • Fukuoka, Japan
    • Kyowa Investigational Site JP-08
  • Fukuoka, Japan
    • Kyowa Investigational Site JP-09
  • Fukuoka, Japan
    • Kyowa Investigational Site JP-12
  • Fukuoka, Japan
    • Kyowa Investigational Site JP-19
  • Fukuoka, Japan
    • Kyowa Investigational Site JP-26
  • Gifu, Japan
    • Kyowa Investigational Site JP-14
  • Hokkaido, Japan
    • Kyowa Investigational Site JP-01
  • Hokkaido, Japan
    • Kyowa Investigational Site JP-02
  • Hokkaido, Japan
    • Kyowa Investigational Site JP-04
  • Hokkaido, Japan
    • Kyowa Investigational Site JP-29
  • Ibaraki, Japan
    • Kyowa Investigational Site JP-31
  • Kagoshima, Japan
    • Kyowa Investigational Site JP-10
  • Kagoshima, Japan
    • Kyowa Investigational Site JP-11
  • Kanagawa, Japan
    • Kyowa Investigational Site JP-05
  • Kanagawa, Japan
    • Kyowa Investigational Site JP-06
  • Kanagawa, Japan
    • Kyowa Investigational Site JP-21
  • Mie, Japan
    • Kyowa Investigational Site JP-18
  • Miyagi, Japan
    • Kyowa Investigational Site JP-20
  • Morioka, Japan
    • Kyowa Investigational Site JP-28
  • Shimane, Japan
    • Kyowa Investigational Site JP-25
  • Tochigi, Japan
    • Kyowa Investigational Site JP-15
  • Tokyo, Japan
    • Kyowa Investigational Site JP-03
  • Tokyo, Japan
    • Kyowa Investigational Site JP-07
  • Tokyo, Japan
    • Kyowa Investigational Site JP-13
  • Tokyo, Japan
    • Kyowa Investigational Site JP-16
  • Tokyo, Japan
    • Kyowa Investigational Site JP-22
  • Tokyo, Japan
    • Kyowa Investigational Site JP-23
  • Tokyo, Japan
    • Kyowa Investigational Site JP-30
• United States
  • California
    • Huntington Beach, California, United States, 92647
      • Kyowa Investigational Site US-19
    • Irvine, California, United States, 92697
      • Kyowa Investigational Site US-17
    • Los Angeles, California, United States, 90033
      • Kyowa Investigational Site US-09
    • Santa Ana, California, United States, 92701
      • Kyowa Investigational Site US-05
  • Colorado
    • Aurora, Colorado, United States, 80010
      • Kyowa Investigational Site US-10
  • Florida
    • Clearwater, Florida, United States, 33756
      • Kyowa Investigational Site US-14
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Kyowa Investigational Site US-04
  • New York
    • New York, New York, United States, 10029
      • Kyowa Investigational Site US-01
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Kyowa Investigational Site US-20
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Kyowa Investigational Site US-11
  • Oregon
    • Portland, Oregon, United States, 97239
      • Kyowa Investigational Site US-08
  • Texas
    • Dallas, Texas, United States, 75230
      • Kyowa Investigational Site US-02
    • Galveston, Texas, United States, 77555
      • Kyowa Investigational Site US-07

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntarily signed informed consent to participate in the study;
• Chronic AD, according to American Academy of Dermatology Consensus Criteria or the local diagnostic criteria, that has been present for at least 1 year before screening;
• EASI score ≥16 at screening and baseline;
• IGA score ≥3 (moderate) at both screening and baseline;
• BSA ≥10% at both screening and baseline;
• Documented recent history (within 1 year prior to screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks).

Exclusion Criteria:

• Current or past history of clinically significant illness(es) deemed by the Investigator to be likely to affect the study conduct and assessments. Examples include, but are not limited to, clinically significant cardiovascular (e.g., New York Heart Association [NYHA] Class III or IV), uncontrolled diabetes (HbA1c ≥9%), liver (e.g., Child-Pugh class B or C), renal, respiratory, hematologic, central nervous system, psychiatric, or autoimmune diseases/disorders;

• Any of the following laboratory abnormalities at screening:

  • Serum creatinine: >1.5 mg/dL
  • AST or ALT: ≥2.5 times the upper limit of normal (ULN)
  • Neutrophil count: <1.5×10³/μL
  • Other laboratory abnormalities that may affect the completion or evaluation of the study, as judged by the Investigator;
• Active malignancies, or onset or a history of treatment of malignancies within 5 years prior to informed consent (except curatively treated in situ cervical carcinoma, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm A; Subcutaneous administration of placebo	Drug: Placebo; Matching placebo
Experimental: Arm B; Subcutaneous administration of KHK4083 (dose level 1, dosing regimen 2)	Drug: KHK4083; Anti-OX40 Monoclonal Antibody KHK4083
Experimental: Arm C; Subcutaneous administration of KHK4083 (dose level 2, dosing regimen 1)	Drug: KHK4083; Anti-OX40 Monoclonal Antibody KHK4083
Experimental: Arm D; Subcutaneous administration of KHK4083 (dose level 3, dosing regimen 1)	Drug: KHK4083; Anti-OX40 Monoclonal Antibody KHK4083
Experimental: Arm E; Subcutaneous administration of KHK4083 (dose level 3, dosing regimen 2)	Drug: KHK4083; Anti-OX40 Monoclonal Antibody KHK4083

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score	In the EASI assessment, the severity of 4 elements of eczema (erythema, induration/papulation, excoriation, and lichenification) at each of 4 body regions (head and neck, trunk, upper extremities, and lower extremities) will be assessed on a scale of 0 to 3 (0 = None , 1 = Mild, 2 = Moderate, 3 = Severe). Half scores (1.5 and 2.5) are allowed, with the exception of 0.5. Any signs must be at least 1 (mild) in severity. In addition, the extent of eczema at each of the 4 body regions will be assessed on a scale of 0 to 6 (0 = 0%, 1 = 1% to 9%, 2 = 10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 89%, 6 = 90% to 100%). Scores calculated according to the expression "total score of 4 elements of eczema × area score of eczema" will be multiplied by 0.1 for head and neck, 0.2 for upper extremities, 0.3 for trunk, and 0.4 for lower extremities. The 4 region scores obtained will then be summed up (maximum score: 72) as EASI score.	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of 50%, 75%, or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI) Score (EASI-50, EASI-75, or EASI-90) at Week 16	In the EASI assessment, the severity of 4 elements of eczema (erythema, induration/papulation, excoriation, and lichenification) at each of 4 body regions (head and neck, trunk, upper extremities, and lower extremities) will be assessed on a scale of 0 to 3 (0 = None , 1 = Mild, 2 = Moderate, 3 = Severe). Half scores (1.5 and 2.5) are allowed, with the exception of 0.5. Any signs must be at least 1 (mild) in severity. In addition, the extent of eczema at each of the 4 body regions will be assessed on a scale of 0 to 6 (0 = 0%, 1 = 1% to 9%, 2 = 10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 89%, 6 = 90% to 100%). Scores calculated according to the expression "total score of 4 elements of eczema × area score of eczema" will be multiplied by 0.1 for head and neck, 0.2 for upper extremities, 0.3 for trunk, and 0.4 for lower extremities. The 4 region scores obtained will then be summed up (maximum score: 72) as EASI score.	Baseline to Week 16
Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score	In the EASI assessment, the severity of 4 elements of eczema (erythema, induration/papulation, excoriation, and lichenification) at each of 4 body regions (head and neck, trunk, upper extremities, and lower extremities) will be assessed on a scale of 0 to 3 (0 = None , 1 = Mild, 2 = Moderate, 3 = Severe). Half scores (1.5 and 2.5) are allowed, with the exception of 0.5. Any signs must be at least 1 (mild) in severity. In addition, the extent of eczema at each of the 4 body regions will be assessed on a scale of 0 to 6 (0 = 0%, 1 = 1% to 9%, 2 = 10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 89%, 6 = 90% to 100%). Scores calculated according to the expression "total score of 4 elements of eczema × area score of eczema" will be multiplied by 0.1 for head and neck, 0.2 for upper extremities, 0.3 for trunk, and 0.4 for lower extremities. The 4 region scores obtained will then be summed up (maximum score: 72) as EASI score.	Baseline to Week 16
Change From Baseline to Week 16 in SCORing Atopic Dermatitis (SCORAD) Score	In the SCORAD assessment, the extent of AD will be calculated as the sum of the percentage of each defined body area, with a maximum score of 100% (assigned as "A" in the overall SCORAD calculation). The severity of 6 specific symptoms of AD will be assessed using the following scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe, with a maximum score of 18 (assigned as "B" in the overall SCORAD calculation). Itch and sleeplessness will be assessed by subjects on a visual analogue scale (VAS), where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum score of 20 (assigned as "C" in the overall SCORAD calculation). The SCORAD score is calculated as A/5 + 7B/2 + C. The maximum possible SCORAD score is 103; higher scores indicate poorer or more severe condition.	Baseline to Week 16
Percent Change From Baseline to Week 16 in SCORing Atopic Dermatitis (SCORAD) Score	In the SCORAD assessment, the extent of AD will be calculated as the sum of the percentage of each defined body area, with a maximum score of 100% (assigned as "A" in the overall SCORAD calculation). The severity of 6 specific symptoms of AD will be assessed using the following scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe, with a maximum score of 18 (assigned as "B" in the overall SCORAD calculation). Itch and sleeplessness will be assessed by subjects on a visual analogue scale (VAS), where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum score of 20 (assigned as "C" in the overall SCORAD calculation). The SCORAD score is calculated as A/5 + 7B/2 + C. The maximum possible SCORAD score is 103; higher scores indicate poorer or more severe condition.	Baseline to Week 16
Achievement of an Investigator's Global Assessment (IGA) Score of 0 or 1 and a Reduction From Baseline of ≥2 Points at Week 16	In the IGA, the Investigator will evaluate the overall skin symptoms of subjects at each visit on a 5-point scale ranging from 0 (clear) to 4 (severe).	Baseline to Week 16
Change From Baseline to Week 16 in Percent Body Surface Area of Involvement of AD (BSA)	The Investigator will calculate the percentage (%) of the total body surface area affected by AD.	Baseline to Week 16
Change From Baseline to Week 16 in Pruritus Numerical Rating Scale (NRS) Score	The worst degree of itch experienced during 24 hours before the time point will be assessed on a Numerical Rating Scale. The degree of itch will be scored on an 11-point scale, with 0 being "no itch" and 10 being the "worst itch imaginable."	Baseline to Week 16
Percent Change From Baseline to Week 16 in Pruritus Numerical Rating Scale (NRS) Score	The worst degree of itch experienced during 24 hours before the time point will be assessed on a Numerical Rating Scale. The degree of itch will be scored on an 11-point scale, with 0 being "no itch" and 10 being the "worst itch imaginable."	Baseline to Week 16
Change From Baseline to Week 16 in Sleep Disturbance Numerical Rating Scale (NRS) Score	Daily sleep disturbance in the last 24 hours before the relevant time point will be assessed on a Numerical Rating Scale. Subjects will score the degree of their sleep disturbance on an 11-point scale ranging from 'no sleep loss' (0) to 'I cannot sleep at all' (10).	Baseline to Week 16
Percent Change From Baseline to Week 16 in Sleep Disturbance Numerical Rating Scale (NRS) Score	Daily sleep disturbance in the last 24 hours before the relevant time point will be assessed on a Numerical Rating Scale. Subjects will score the degree of their sleep disturbance on an 11-point scale ranging from 'no sleep loss' (0) to 'I cannot sleep at all' (10).	Baseline to Week 16
Change From Baseline to Week 16 in Dermatology Life Quality Index (DLQI)	DLQI consists of 6 subscales (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment), which are scored from 0 to 3 on the basis of 10 questions. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more QoL is impaired.	Baseline to Week 16
EASI Score at Each Time Point	In the EASI assessment, the severity of 4 elements of eczema (erythema, induration/papulation, excoriation, and lichenification) at each of 4 body regions (head and neck, trunk, upper extremities, and lower extremities) will be assessed on a scale of 0 to 3 (0 = None , 1 = Mild, 2 = Moderate, 3 = Severe). Half scores (1.5 and 2.5) are allowed, with the exception of 0.5. Any signs must be at least 1 (mild) in severity. In addition, the extent of eczema at each of the 4 body regions will be assessed on a scale of 0 to 6 (0 = 0%, 1 = 1% to 9%, 2 = 10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 89%, 6 = 90% to 100%). Scores calculated according to the expression "total score of 4 elements of eczema × area score of eczema" will be multiplied by 0.1 for head and neck, 0.2 for upper extremities, 0.3 for trunk, and 0.4 for lower extremities. The 4 region scores obtained will then be summed up (maximum score: 72) as EASI score.	56 Weeks
Percent Change From Baseline in EASI Score at Each Time Point	In the EASI assessment, the severity of 4 elements of eczema (erythema, induration/papulation, excoriation, and lichenification) at each of 4 body regions (head and neck, trunk, upper extremities, and lower extremities) will be assessed on a scale of 0 to 3 (0 = None , 1 = Mild, 2 = Moderate, 3 = Severe). Half scores (1.5 and 2.5) are allowed, with the exception of 0.5. Any signs must be at least 1 (mild) in severity. In addition, the extent of eczema at each of the 4 body regions will be assessed on a scale of 0 to 6 (0 = 0%, 1 = 1% to 9%, 2 = 10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 89%, 6 = 90% to 100%). Scores calculated according to the expression "total score of 4 elements of eczema × area score of eczema" will be multiplied by 0.1 for head and neck, 0.2 for upper extremities, 0.3 for trunk, and 0.4 for lower extremities. The 4 region scores obtained will then be summed up (maximum score: 72) as EASI score.	56 Weeks
Achievement of EASI-50, EASI-75, or EASI-90 at Each Time Point	In the EASI assessment, the severity of 4 elements of eczema (erythema, induration/papulation, excoriation, and lichenification) at each of 4 body regions (head and neck, trunk, upper extremities, and lower extremities) will be assessed on a scale of 0 to 3 (0 = None , 1 = Mild, 2 = Moderate, 3 = Severe). Half scores (1.5 and 2.5) are allowed, with the exception of 0.5. Any signs must be at least 1 (mild) in severity. In addition, the extent of eczema at each of the 4 body regions will be assessed on a scale of 0 to 6 (0 = 0%, 1 = 1% to 9%, 2 = 10% to 29%, 3 = 30% to 49%, 4 = 50% to 69%, 5 = 70% to 89%, 6 = 90% to 100%).	56 Weeks
SCORing Atopic Dermatitis (SCORAD) Score at Each Time Point	In the SCORAD assessment, the extent of AD will be calculated as the sum of the percentage of each defined body area, with a maximum score of 100% (assigned as "A" in the overall SCORAD calculation). The severity of 6 specific symptoms of AD will be assessed using the following scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe, with a maximum score of 18 (assigned as "B" in the overall SCORAD calculation). Itch and sleeplessness will be assessed by subjects on a visual analogue scale (VAS), where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum score of 20 (assigned as "C" in the overall SCORAD calculation). The SCORAD score is calculated as A/5 + 7B/2 + C. The maximum possible SCORAD score is 103; higher scores indicate poorer or more severe condition.	56 Weeks
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Each Time Point	In the SCORAD assessment, the extent of AD will be calculated as the sum of the percentage of each defined body area, with a maximum score of 100% (assigned as "A" in the overall SCORAD calculation). The severity of 6 specific symptoms of AD will be assessed using the following scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe, with a maximum score of 18 (assigned as "B" in the overall SCORAD calculation). Itch and sleeplessness will be assessed by subjects on a visual analogue scale (VAS), where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), with a maximum score of 20 (assigned as "C" in the overall SCORAD calculation). The SCORAD score is calculated as A/5 + 7B/2 + C. The maximum possible SCORAD score is 103; higher scores indicate poorer or more severe condition.	56 Weeks
Achievement of an Investigator's Global Assessment (IGA) Score of 0 or 1 and a Reduction From Baseline of ≥2 Points at Each Time Point	In the IGA, the Investigator will evaluate the overall skin symptoms of subjects at each visit on a 5-point scale ranging from 0 (clear) to 4 (severe)	56 Weeks
Change From Baseline in Percent Body Surface Area (BSA) at Each Time Point	The Investigator will calculate the percentage (%) of the total body surface area affected by AD.	56 Weeks
Pruritus Numerical Rating Scale (NRS) Score at Each Time Point	The worst degree of itch experienced during 24 hours before the time point will be assessed on a Numerical Rating Scale. The degree of itch will be scored on an 11-point scale, with 0 being "no itch" and 10 being the "worst itch imaginable."	56 Weeks
Percent Change From Baseline in Pruritus Numerical Rating Scale (NRS) Score at Each Time Point	The worst degree of itch experienced during 24 hours before the time point will be assessed on a Numerical Rating Scale. The degree of itch will be scored on an 11-point scale, with 0 being "no itch" and 10 being the "worst itch imaginable."	56 Weeks
Sleep Disturbance Numerical Rating Scale (NRS) Score at Each Time Point	Daily sleep disturbance in the last 24 hours before the relevant time point will be assessed on a Numerical Rating Scale. Subjects will score the degree of their sleep disturbance on an 11-point scale ranging from 'no sleep loss' (0) to 'I cannot sleep at all' (10).	56 Weeks
Percent Change From Baseline in Sleep Disturbance Numerical Rating Scale (NRS) Score at Each Time Point	Daily sleep disturbance in the last 24 hours before the relevant time point will be assessed on a Numerical Rating Scale. Subjects will score the degree of their sleep disturbance on an 11-point scale ranging from 'no sleep loss' (0) to 'I cannot sleep at all' (10).	56 Weeks
Dermatology Life Quality Index (DLQI) at Each Time Point	DLQI consists of 6 subscales (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment), which are scored from 0 to 3 on the basis of 10 questions. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more QoL is impaired.	56 Weeks

Collaborators and Investigators

• Sponsor: Kyowa Kirin, Inc.
• Collaborators: Kyowa Kirin Co., Ltd.
• Investigators: Study Director: Ehsanollah Esfandiari, MD, PhD, Kyowa Kirin Pharmaceutical International Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2018
• Primary Completion (Actual): February 6, 2020
• Study Completion (Actual): November 12, 2020

Study Registration Dates

• First Submitted: October 9, 2018
• First Submitted That Met QC Criteria: October 9, 2018
• First Posted (Actual): October 11, 2018

Study Record Updates

• Last Update Posted (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: eczema; skin diseases; AD; biologics
• 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; Dermatologic Agents; KHK4083
• Other Study ID Numbers: 4083-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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