Brief Summary
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.
Brief Title
Study of an Anti-OX40 Monoclonal Antibody (KHK4083) in Subjects With Moderate to Severe Atopic Dermatitis
Categories
Completion Date
Completion Date Type
Actual
Conditions
Atopic Dermatitis
Eligibility Criteria
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).
* 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).
Inclusion Criteria
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).
* 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).
Gender
All
Gender Based
false
Keywords
AD
eczema
skin diseases
biologics
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03703102
Org Class
Industry
Org Full Name
Kyowa Kirin Co., Ltd.
Org Study Id
4083-006
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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)
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score
Outcome Time Frame
Baseline to Week 16
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Baseline to Week 16
Outcome Measure
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
Outcome Description
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.
Outcome Time Frame
Baseline to Week 16
Outcome Measure
Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score
Outcome Description
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.
Outcome Time Frame
Baseline to Week 16
Outcome Measure
Change From Baseline to Week 16 in SCORing Atopic Dermatitis (SCORAD) Score
Outcome Description
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.
Outcome Time Frame
Baseline to Week 16
Outcome Measure
Percent Change From Baseline to Week 16 in SCORing Atopic Dermatitis (SCORAD) Score
Outcome Description
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).
Outcome Time Frame
Baseline to Week 16
Outcome Measure
Achievement of an Investigator's Global Assessment (IGA) Score of 0 or 1 and a Reduction From Baseline of ≥2 Points at Week 16
Outcome Description
The Investigator will calculate the percentage (%) of the total body surface area affected by AD.
Outcome Time Frame
Baseline to Week 16
Outcome Measure
Change From Baseline to Week 16 in Percent Body Surface Area of Involvement of AD (BSA)
Outcome Description
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."
Outcome Time Frame
Baseline to Week 16
Outcome Measure
Change From Baseline to Week 16 in Pruritus Numerical Rating Scale (NRS) Score
Outcome Description
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."
Outcome Time Frame
Baseline to Week 16
Outcome Measure
Percent Change From Baseline to Week 16 in Pruritus Numerical Rating Scale (NRS) Score
Outcome Description
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).
Outcome Time Frame
Baseline to Week 16
Outcome Measure
Change From Baseline to Week 16 in Sleep Disturbance Numerical Rating Scale (NRS) Score
Outcome Description
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).
Outcome Time Frame
Baseline to Week 16
Outcome Measure
Percent Change From Baseline to Week 16 in Sleep Disturbance Numerical Rating Scale (NRS) Score
Outcome Description
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.
Outcome Time Frame
Baseline to Week 16
Outcome Measure
Change From Baseline to Week 16 in Dermatology Life Quality Index (DLQI)
Outcome Description
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.
Outcome Time Frame
56 Weeks
Outcome Measure
EASI Score at Each Time Point
Outcome Description
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.
Outcome Time Frame
56 Weeks
Outcome Measure
Percent Change From Baseline in EASI Score at Each Time Point
Outcome Description
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%).
Outcome Time Frame
56 Weeks
Outcome Measure
Achievement of EASI-50, EASI-75, or EASI-90 at Each Time Point
Outcome Description
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.
Outcome Time Frame
56 Weeks
Outcome Measure
SCORing Atopic Dermatitis (SCORAD) Score at Each Time Point
Outcome Description
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.
Outcome Time Frame
56 Weeks
Outcome Measure
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Each Time Point
Outcome Description
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)
Outcome Time Frame
56 Weeks
Outcome Measure
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
Outcome Description
The Investigator will calculate the percentage (%) of the total body surface area affected by AD.
Outcome Time Frame
56 Weeks
Outcome Measure
Change From Baseline in Percent Body Surface Area (BSA) at Each Time Point
Outcome Description
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."
Outcome Time Frame
56 Weeks
Outcome Measure
Pruritus Numerical Rating Scale (NRS) Score at Each Time Point
Outcome Description
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."
Outcome Time Frame
56 Weeks
Outcome Measure
Percent Change From Baseline in Pruritus Numerical Rating Scale (NRS) Score at Each Time Point
Outcome Description
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).
Outcome Time Frame
56 Weeks
Outcome Measure
Sleep Disturbance Numerical Rating Scale (NRS) Score at Each Time Point
Outcome Description
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).
Outcome Time Frame
56 Weeks
Outcome Measure
Percent Change From Baseline in Sleep Disturbance Numerical Rating Scale (NRS) Score at Each Time Point
Outcome Description
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.
Outcome Time Frame
56 Weeks
Outcome Measure
Dermatology Life Quality Index (DLQI) at Each Time Point
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Holly Kanavy
Investigator Email
HKanavy@montefiore.org
Investigator Phone
866-633-8255 / 718-230-2997 / 510-996-0741