Approximately 600 subjects will be enrolled in the study, of which at least 150 subjects aged 2-6; at least 140 subjects aged 7-11; at least 120 subjects aged 12-17 and up to 90 subjects will be adults. Subjects must have mild-moderate AD involving at least 5% treatable %BSA assessed on baseline/Day 1. Treatable %BSA will be defined as the percent of a subject's total body surface area that is AD involved, excluding the scalp.
Eligible subjects will be randomized at the Baseline/Day 1 visit. Randomization will be stratified by eligibility for TCS or TCI treatment as per national approved labels. Cohort 1 will be for subjects who are eligible for TCS therapy, and Cohort 2 will be for subjects who are not eligible for TCS therapy but eligible for TCI therapy. The investigational products will be applied BID for 28 days to the Treatable body surface area (BSA) identified at Baseline/Day 1.
The primary efficacy endpoint is the percent change from baseline in the Eczema Area and Severity Index (EASI) total score at Day 29.
For the efficacy comparison of crisaborole versus vehicle, subjects from both Cohort 1 and Cohort 2 are included in the analysis, adjusted for cohort effect. For the efficacy comparison of crisaborole versus TCS, only subjects from Cohort 1 are included in the analysis. For the comparison of crisaborole versus TCI, only subjects from Cohort 2 are included in the analysis.
Safety and efficacy assessments will be conducted at the investigator site by a clinical assessor blinded to treatment assignment.
Scheduled study visits for all subjects will occur at Screening, Baseline/Day 1, Day 8, Day 15, Day 22, Day 29 (End of treatment/Early termination), Day 43 or 14 Days after last dose if subject is terminated early from treatment. A follow up telephone call will be made by site staff to the subjects/subject's legally acceptable guardian(s) on Day 60 or at least 28 days after last dose if subject is terminated early from treatment. The Day 60 visit will be completed in the clinic for subjects enrolled in the OCT sub-study.
To further explore the benefit/risk of crisaborole ointment, 2%, a sub-study to evaluate differences in atrophic skin changes across study treatment groups in Cohort 1 will be conducted at select sites.
The sub-study will include obtaining Optical coherence tomography (OCT) imaging to evaluate atrophic changes in epidermal thickness during and after treatment with study investigational product in Cohort 1. This sub-study also provides an opportunity to explore differences in Transepidermal Water Loss (TEWL) and cutaneous inflammatory and barrier biomarkers associated with AD within the stratum corneum (SC) across treatment groups in Cohort 1. The Aquaflux (an evaporimeter) will be used in this sub-study to evaluate TEWL during and after treatment at select sub-study centers. Tape-strips will also be used in this sub-study to evaluate SC biomarkers from AD lesional and non-lesional skin.
This sub-study will include approximately 60 subjects from Cohort 1 that are enrolled in the main study (C3291037). Subjects will follow the main study assessments and visits as per the schedule of activities for the main study but will also follow additional procedures as described in the protocol. The telephone call at Day 60 in the main study is replaced with an in-clinic visit for sub-study participants.