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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: KHK4083
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

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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No

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
Interventional Model Description: subcutaneous administration
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AD, eczema, skin diseases, biologics