A Study of Crisaborole Ointment 2%; Crisaborole Vehicle; TCS and TCI in Subjects Aged ≥ 2 Years, With Mild-moderate AD

Hematology parameters included with criteria greater than (\>) 1.2\*upper limit of normal (ULN): leukocytes (10\^3 per cubic millimeter \[10\^3/mm\^3\]), lymphocytes (10\^3/mm\^3), lymphocytes/leukocytes (%), neutrophils (10\^3/mm\^3), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils (10\^3/mm\^3), eosinophils/leukocytes (%), monocytes (10\^3/mm\^3), monocytes/leukocytes (%). Clinical chemistry included parameters: aspartate aminotransferase (units per liter \[U/L\]) (\>3.0\* ULN), alanine aminotransferase (U/L) (\>3.0\* ULN), alkaline phosphatase (U/L) (\>3.0\* ULN), creatinine (milligram per deciliter \[mg/dL\]) (\>1.3\* ULN), potassium (milliequivalent per liter \[mEq/L\]) (\>1.1\* ULN), bicarbonate (mEq/L) (\>1.1\* ULN).

Time frame: Screening up to Day 29

Population: Safety analysis set included all participants who received at least 1 dose of the investigational product according to actual treatment received.

Vital sign measurements included temperature, respiratory rate, pulse rate, and blood pressure. Temperature, respiratory rate, pulse rate, and blood pressure were taken in the seated or supine position, after the participant has been sitting or lying calmly for a minimum of 5 minutes (when possible for younger children). Position of recording was consistent within participant through-out the study.

Time frame: Screening up to Day 29

Population: Safety analysis set included all participants who received at least 1 dose of the investigational product according to actual treatment received.

Local tolerability AEs included application and instillation site reactions, application site discharge, application site erythema, application site exfoliation, application site pain, application site pruritus, application site swelling, dermatitis and eczema, dermatitis atopic, dermatitis contact, eczema, skin irritation, telangiectasia and related conditions, and urticarias.

Time frame: From Baseline up to 28 days after last dose of study treatment (maximum up to 60 Days)

Population: Safety analysis set included all participants who received at least 1 dose of the investigational product according to actual treatment received.

An AE is any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. TEAEs are events between the first dose of study drug up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A SAE is any untoward medical occurrence at any dose that: results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event.

Time frame: From Baseline up to 28 days after last dose of study treatment (maximum up to 60 Days)

Population: Safety analysis set included all participants who received at least 1 dose of the investigational product according to actual treatment received.

EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and percent (%) body surface area (%BSA) affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck \[h\], upper limbs \[u\], trunk \[t\] \[including axillae, groin\], lower limbs \[l\] \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score (A) based upon %BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%), 6 (90 to 100%). Total EASI score (aged \>=8 years) =0.1\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et + It +Ext + Lt) + 0.4\*Al\*(El + Il + Exl + Ll); for aged 2 to \<8 years =0.2\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et +It + Ext + Lt) + 0.3\*Al\*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.

Time frame: Baseline, Day 29

Population: FAS included all randomized participants who received at least 1 dose of investigational product. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure.

The CDLQI was a 10-item questionnaire that measures the impact of skin disease on children's (aged 4 to 15 years) quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The CDLQI total score was the sum of individual scores of question 1-10 and ranged from 0 (not at all) to 30 (very much): 0-1 = no effect on the child's life; 2-6 = small effect; 7-12 = moderate effect; 13-18 = very large effect; 19-30 = extremely large effect. Higher scores indicated more impact on quality of life of children.

Time frame: Baseline, Day 8, 15, 22 and 29

Population: Analysis was performed on all participants aged 4 to 15 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, Overall Number of Participants Analyzed = participants evaluable for this outcome measure and 'number analyzed' = participants evaluable for each specified row.

The DFI was a 10-item disease questionnaire that measures the impact of having a child (aged 2-17 years) with AD on family quality of life. It was completed by parent/legal guardian of the child (affected by AD), based on recall over the past week. Each question was scored on a 4-point scale ranging from 0 (not at all) to 30 (very much): where higher scores indicated worst quality of life of family. The DFI total score was the sum of individual scores of the 10 questions and ranged from 0 (no impact on life of family) to 30 (maximum effect on life of family), where higher DFI scores indicated maximum effect on life of family.

Time frame: Baseline, Day 8, 15, 22 and 29

Population: Analysis was performed on all participants aged 2 to 17 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, Overall Number of Participants Analyzed = participants evaluable for this outcome measure and 'number analyzed' = participants evaluable for each specified row.

DLQI is a 10-item questionnaire that measures the impact of skin disease on participants aged \>=16 years. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participant.

Time frame: Baseline, Day 8, 15, 22 and 29

Population: Analysis was performed on all participants aged \>=16 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.

The severity of itch (pruritus) due to AD was assessed using the participant reported itch severity scale for participants aged \<6 years. Participant's caregivers at specified time points were asked the following question how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?. The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

Time frame: Baseline, Day 8, 15, 22 and 29

Population: Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

The severity of itch (pruritus) due to AD was assessed using the five-category participant reported itch severity scale for participants aged 6-11 years. Participants at specified time points were asked to circle the face that shows how itchy your skin has been today. The scale ranged from 0 to 4, where 0= no itch and 4= very itch. Higher scores indicated worse itch.

Time frame: Baseline, Day 8, 15, 22 and 29

Population: Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged \>=12 years. Participants at specified time points were asked the following question: how would you rate your itch at the worst moment during the previous 24 hours? The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

Time frame: Baseline, Day 8, 15, 22 and 29

Population: Analysis was performed on all participants aged \>=12 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure and 'number analyzed' signifies number of participants evaluable for each specified row.

Four body regions were evaluated: head and neck, upper limbs, trunk (including axillae) and lower limbs (including buttocks) excluding scalp. BSA was calculated using handprint method. Number of handprints (size of participant's full palmer hand in a closed position) fitting in affected area of a body region was estimated. Maximum number of handprints were: 10 for head, neck (20 for \<8 years age), 20 for upper limbs, 30 for trunk, 40 for lower limbs (30 for \<8 years age). Surface area (SA) of body region equivalent to 1 handprint: 10% for head, neck (5% for \<8 years age), 5% for upper limbs, 3.33% for trunk, 2.5% for lower limbs (3.33% for \<8 years age). Overall %BSA for a body region = total number of handprints in a body region \* % SA equivalent to 1 handprint. % BSA for an individual: mean of % BSA of all 4 body regions, range =0-100%, higher values = greater AD severity.

Time frame: Baseline, Day 8, 15, 22 and 29

Population: FAS included all randomized participants who received at least 1 dose of investigational product. Here 'number analyzed' signifies number of participants evaluable for each specified row.

The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged \>=12 years. Participants at specified time points were asked the following question: how would you rate your itch at the worst moment during the previous 24 hours? The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

Time frame: Day 8, 15, 22 and 29

Population: Analysis was performed on all participants aged \>=12 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure.

The severity of itch (pruritus) due to AD was assessed using the Peak Pruritus NRS for participants aged \>=12 years. Participants at specified time points were asked the following question: how would you rate your itch at the worst moment during the previous 24 hours? The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

Time frame: Day 8, 15, 22 and 29

Population: Analysis was performed on all participants aged \>=12 years from FAS, and FAS included all randomized participants who received at least 1 dose of investigational product. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure.

The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged \<6 years. Participant's caregivers at specified time points were asked the following question how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?. The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

Time frame: Day 8, 15, 22 and 29

Population: Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged \<6 years. Participant's caregivers at specified time points were asked the following question how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?. The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

Time frame: Day 8, 15, 22 and 29

Population: Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck \[h\], upper limbs \[u\], trunk \[t\] \[including axillae, groin\], lower limbs \[l\] \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%), 6 (90 to 100%). Total EASI score (aged \>=8 years) =0.1\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et + It +Ext + Lt) + 0.4\*Al\*(El + Il + Exl + Ll); for aged 2 to \<8 years =0.2\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et +It + Ext + Lt) + 0.3\*Al\*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.

Time frame: Day 8, 15, 22 and 29

Population: FAS included all randomized participants who received at least 1 dose of investigational product. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure.

ISGA is a five point global assessment scale of AD severity, used to characterize participants' overall disease severity across all treatable AD lesions (excluding the scalp). ISGA score ranged from 0 to 4: where 0 = clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity of AD.

Time frame: Day 8, 15, 22 and 29

Population: FAS included all randomized participants who received at least 1 dose of investigational product.

ISGA is a five point global assessment scale of AD severity, used to characterize participants' overall disease severity across all treatable AD lesions (excluding the scalp). ISGA score ranged from 0 to 4: where 0= clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity of AD.

Time frame: Day 8, 15, 22 and 29

Population: FAS included all randomized participants who received at least 1 dose of investigational product.

EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck \[h\], upper limbs \[u\], trunk \[t\] \[including axillae, groin\], lower limbs \[l\] \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%), 6 (90 to 100%). Total EASI score (aged \>=8 years) =0.1\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et + It +Ext + Lt) + 0.4\*Al\*(El + Il + Exl + Ll); for aged 2 to \<8 years =0.2\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et +It + Ext + Lt) + 0.3\*Al\*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.

Time frame: Baseline, Day 8, 15 and 22

Population: FAS included all randomized participants who received at least 1 dose of investigational product. Here, 'number analyzed' signifies number of participants evaluable for each specified row.

The severity of itch (pruritus) due to AD was assessed using the patient reported itch severity scale for participants aged \<6 years. Participant's caregivers at specified time points were asked the following question how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?. The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

Time frame: Baseline up to Day 29

Population: Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged \<6 years. Participant's caregivers at specified time points were asked the following question how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?. The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

Time frame: Baseline up to Day 29

Population: Data was not summarized as per SAP which was revised prior to the analyses and which reflect limitations related to reduced sample size (39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Pruritus related PRO endpoints used different instruments in each of 3 age groups. As a result, subdividing population based on age group renders smaller sample size in pediatric groups, therefore data was not summarized.

The severity of itch (pruritus) due to AD was assessed using the Peak Pruritus NRS for participants aged \>12 years. Participants at specified time points were asked the following question: how would you rate your itch at the worst moment during the previous 24 hours? The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

Time frame: Baseline up to Day 29

Population: Data was not summarized as per SAP which was revised prior to the analyses and which reflected limitations related to reduced sample size (only 39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Summarizing further by Time to \>3 Point Improvement will not provide additional useful information due to smaller than planned sample size as a result of study early termination.

EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck \[h\], upper limbs \[u\], trunk \[t\] \[including axillae, groin\], lower limbs \[l\] \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%), 6 (90 to 100%). Total EASI score (aged \>=8 years) =0.1\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et + It +Ext + Lt) + 0.4\*Al\*(El + Il + Exl + Ll); for aged 2 to \<8 years =0.2\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et +It + Ext + Lt) + 0.3\*Al\*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.

Time frame: Baseline up to Day 43

Population: FAS included all randomized participants who received at least 1 dose of investigational product. Here, Overall Number of Participants Analyzed= participants evaluable for this outcome measure.

The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged \>12 years. Participants at specified time points were asked the following question: how would you rate your itch at the worst moment during the previous 24 hours? The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.

Time frame: Baseline up to Day 29

Population: Data was not summarized as per SAP which was revised prior to the analyses and which reflected limitations related to reduced sample size (only 39% enrollment) of early terminated study. Smaller than originally planned sample size was insufficient to allow robust statistical analyses. Summarizing further by Time to \>2 Point Improvement will not provide additional useful information due to smaller than planned sample size as a result of study early termination.