Study to Assess Efficacy and Safety of Two Regimens of Crisaborole Ointment 2% in Japanese Participants Aged ≥2 Years With Mild to Moderate Atopic Dermatitis

Study Overview
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Brief Summary
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This is a Phase 2b, multi-center, randomized, double-blind, vehicle-controlled, intraparticipant study to evaluate efficacy and safety of two regimens of crisaborole ointment 2% in Japanese pediatric and adult participants (cohort 1: 12 years and older, cohort 2: 2 to under 12 years old) with mild to moderate Atopic Dermatitis (AD).

Official Title
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A Phase 2b, Multi Center, Randomized, Double-Blind, Vehicle-Controlled, Intra-Participant Study, to Evaluate Efficacy and Safety of Two Regimens of Crisaborole Ointment 2% in Japanese Pediatric and Adult Participants (2 Years and Older) With Mild to Moderate Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Crisaborole ointment 2%
* Drug: Vehicle
* Drug: Crisaborole ointment 2%
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants ages; Cohort 1: 12 years and older at the time of consent. Cohort 2: 2 years to under 12 years old at the time of consent. Has confrimed clinical diagnosis of active AD according to Hanifin and Rajka criteria and has at least 6 months history prior to screening and has been clinically stable for more than 1 month Has at least 1% and no more than 30% BSA at baseline/Day1, excluding scalp, genitals and groin area Has a Investigator's static global assessment (ISGA) score of Mild (2) or Moderate (3) on Day 1. Exclusion Criteria: Has other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. Participants had previous treatment with any topical or systemic PDE-4 inhibitor.

Ages Eligible for Study
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Minimum Age: 2 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crisaborole ointment 2% once daily (QD) vs vehicle QD<br>intra-participant comparison, treatment will be randomly assigned to target lesion 1 and lesion 2. | Drug: Crisaborole ointment 2%<br>* QD regimen<br>Drug: Vehicle<br>* QD regimen<br>|
| Experimental: Crisaborole ointment 2% twice daily (BID) vs vehicle BID<br>Intra-participant comparison, treatment will be randomly assigned to target lesion 1 and lesion 2. | Drug: Crisaborole ointment 2%<br>* BID regimen<br>Drug: Vehicle<br>* BID regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Sign Score (TSS) in Target Lesions at Day 15: Crisaborole Ointment 2% Versus Vehicle | Lesion TSS was an assessment of the target lesion severity, which was based on severity of 4 clinical signs erythema, induration/papulation, excoriation and lichenification. All of these 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). These ratings were added to create a total TSS score; ranging from 0 (none) to 12 (most severe), with higher score representing greater severity. | Baseline, Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Sign Score in Target Lesions at Day 15: Crisaborole Ointment 2% BID Versus Crisaborole Ointment 2% QD | Lesion TSS was an assessment of the target lesion severity, which was based on severity of 4 clinical signs erythema, induration/papulation, excoriation and lichenification. All of these 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). These ratings were added to create a total TSS score; ranging from 0 (none) to 12 (most severe), with higher score representing greater severity. | Baseline, Day 15 | 
| Change From Baseline in Total Sign Score in Target Lesions at Day 8: Crisaborole Ointment 2% Versus Vehicle | Lesion TSS was an assessment of the target lesion severity, which was based on severity of 4 clinical signs erythema, induration/papulation, excoriation and lichenification. All of these 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). These ratings were added to create a total TSS score; ranging from 0 (none) to 12 (most severe), with higher score representing greater severity. | Baseline, Day 8 | 
| Change From Baseline in Investigator's Static Global Assessment (ISGA) Score in Target Lesions at Day 8 and Day 15 | ISGA assessed the severity of AD on a 5-point scale ranged from 0 (clear) to 4 (severe), where higher scores indicated higher degree of AD. Grades for classification of severity: 0= clear (minor residual hypo/hyper pigmentation, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). | Baseline, Day 8, Day 15 | 
| Change From Baseline in Peak Pruritus Numerical Rating Scale (NRS) in Target Lesions up to Day 15 in Participants Aged 12 Years or More | The severity of itch (pruritus) due to AD at the target lesion was assessed using the peak pruritus NRS. Participants aged 12 years or more, were asked to rate their itch severity at the worst moment during the past 24 hours on a scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores represented more severe itch. | Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 | 
| Change From Baseline in Itch Severity Scale in Target Lesions up to Day 15 in Participants Aged Between 6 to 11 Years | The itch severity scale was used for participants >=6 to 11 years of age to assess severity of itch (pruritus) due to AD at the target lesion. In this assessment, participants were asked to choose a unit that showed how itchy their skin had been on day of assessment on a 5-point scale ranging from 1= not itchy to 5= very itchy, where higher scores represented more severe itch. | Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 | 
| Change From Baseline in Observer Reported Itch Severity Numerical Rating Scale in Target Lesions up to Day 15 in Participants Aged Between 2 to 11 Years | Observer reported itch severity NRS was used for participants >=2 and < 12 years of age to assess severity of itch (pruritus) due to AD at the target lesion. Parents/caregivers (of participants) were asked to rate participants' itch (i.e. scratching, rubbing) at the worst moment during past 24 hours on a scale of 0 (no itch) to 10 (worst itch imaginable); higher scores represented more severe itch. | Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) in the Target Lesions Per Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term | An AE was any untoward medical occurrence attributed to a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to end of study that were absent before treatment or that worsened relative to pre-treatment state. For this outcome measure, treatment-emergent AEs occurred at each treated target lesion were summarized. MedDRA version 22.1 coding dictionary was used. | Day 1 up to 35 days after end of treatment (maximum up to Day 50) | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) by Treatment Regimen | An AE was any untoward medical occurrence attributed to a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to end of study that were absent before treatment or that worsened relative to pre-treatment state. | Day 1 up to 35 days after end of treatment (maximum up to Day 50) |