A Study of Crisaborole Ointment 2% in Children Aged 3-24 Months With Mild to Moderate Atopic Dermatitis

Study Overview
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Brief Summary
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This 4-week study will evaluate the safety, pharmacokinetics (PK), and efficacy of crisaborole ointment 2%, applied twice daily (BID) in subjects who are 3 months to less than 24 months of age with mild-to-moderate AD.

Detailed Description
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Approximately 125 subjects will be enrolled. Subjects must have mild-to-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. In addition, a cohort of at least 16 of the 125 subjects will be included in a subgroup for PK assessment. These subjects must have moderate AD and a minimum of 35% treatable %BSA, excluding the scalp, and must complete all PK assessments to be included in the PK analysis. Of these subjects, at least 3 subjects who are less than 9 months of age will be enrolled. Subjects discontinuing for reasons other than treatment emergent adverse event ( TEAE) may be replaced at the discretion of the sponsor to ensure 16 subjects complete the PK assessments. Only selected study sites will participate in the PK assessment. Scheduled study visits/telephone contacts for all subjects will occur at Screening (up to 28 days prior to Baseline/Day 1), Baseline/Day 1, Day 8, Day 15, Day 22, Day 29 (end of treatment/early termination), Day 36, and Day 57 (end of study).

Official Title
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A PHASE 4, MULTICENTER, OPEN-LABEL SAFETY STUDY OF CRISABOROLE OINTMENT 2% IN CHILDREN AGED 3 MONTHS TO LESS THAN 24 MONTHS WITH MILD TO MODERATE ATOPIC DERMATITIS

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Crisaborole ointment 2%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 3 months at the screening visit to < 24 months on baseline/Day 1, diagnosed with AD Exclusion Criteria: Subjects with any clinically significant dermatological condition or disease (including active or potentially recurrent non-AD dermatological conditions that overlap with AD such as Netherton Syndrome)

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 23 Months

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crisaborole ointment 2%<br>Subjects will be dosed for 28 days. A thin layer of ointment will be applied to all areas designated for treatment. | Drug: Crisaborole ointment 2%<br>* Applied BID<br>* Other names: Eucrisa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs) and Site Reactions | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. 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; medically important events. Treatment-emergent were events between first dose of investigational product and up to 28 days after the last dose of investigational product that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. Site reactions are reactions which occurred in participants at the site of application of investigational product. | Baseline (Day 1) up to at least 28 days after last dose of investigational product (up to 60 days) | 
| Number of Participants With Clinically Significant Height Values Meeting Pre-defined Criteria | Height of participants was measured in terms of centimeter (cm). The pre-defined criteria for measuring the height was less than (<) 55 cm and greater than (>) 92.5 cm. | Baseline (Day 1) up to Day 29 (end of treatment) | 
| Number of Participants With Clinically Significant Weight Values Meeting Pre-defined Criteria | Weight of participants was measured in terms of kilogram (kg). The pre-defined criteria of measuring the weight of participants was less than equal to (<=) 4.5 kg and >15 kg. | Baseline (Day 1) up to Day 29 (end of treatment) | 
| Number of Participants With Clinically Significant Blood Pressure Values Meeting Pre-defined Criteria | Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) of participants was measured in terms of millimeters of mercury (mmHg). The clinically significant pre-defined criteria were, SBP: change of greater than equal to (>=) 30 mmHg increase from baseline (IFB) and SBP change of >= 30 mmHg decrease from baseline (DFB); DBP: change of >=20 mmHg IFB and DBP change of >=20 mmHg DFB. | Baseline (Day 1) up to Day 29 (end of treatment) | 
| Number of Participants With Clinically Significant Pulse Rate Values Meeting Pre-defined Criteria | Pulse rate of participants was measured in terms of beats per minute (bpm). The pre-defined criteria of measuring the pulse rate of participants was <90 bpm and >180 bpm. | Baseline (Day 1) up to Day 29 (end of treatment) | 
| Number of Participants With Clinically Significant Respiratory Rate Values Meeting Pre-defined Criteria | Respiratory rate was measured in terms of number of breaths per minute. The pre-defined criteria of measuring the respiratory rate of participants was < 22 breaths per min and > 53 breaths per min. | Baseline (Day 1) up to Day 29 (end of treatment) | 
| Number of Participants With Clinically Significant Body Temperature Values Meeting Pre-defined Criteria | Body temperature of participants was measured in degree Celsius. The normal body temperature value was >= 39 degree Celsius. | Baseline (Day 1) up to Day 29 (end of treatment) | 
| Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Values Meeting Pre-defined Criteria | ECG of participants was measured in terms of millisecond (msec). ECG parameters included pulse rate (PR) interval, QRS interval, corrected QT interval using Fridericia's formula (QTcF). ECG values meeting pre-defined criteria were 1) PR interval: greater than equal to (>=) 25 percent (%) increase when baseline greater than (>)200 milliseconds (msec); or increase >=50% when baseline less than or equal to (<=200) msec; 2) QRS interval: >=25% increase when baseline >100 msec; >=50% increase when baseline <= 100 msec; 3) QTCF interval: QTc interval using Fridericia's formula (QTcF interval) > 30 msec. IFB stands for increase from baseline. | Baseline (Day 1) up to Day 29 (end of treatment) | 
| Number of Participants With Clinically Significant Laboratory Parameters Meeting Pre-defined Criteria | Criteria: hematology: hemoglobin, hematocrit, erythrocytes < 0.8*lower limit of normal (LLN), platelets <0.5*LLN >1.75*upper limit of normal (ULN), leukocytes <0.6* LLN >1.5* ULN, lymphocytes, lymphocytes/leukocytes, neutrophils, neutrophils/leukocytes <0.8* LLN >1.2* ULN, basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes monocytes monocytes/leukocytes >1.2*ULN. Clinical chemistry: bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase >3.0*ULN, protein, albumin <0.8* LLN >1.2* ULN, blood urea nitrogen, creatinine >1.3* ULN, sodium <0.95*LLN >1.05*ULN, potassium, chloride, bicarbonate <0.9* LLN >1.1* ULN, glucose <0.6*LLN >1.5*ULN. | Baseline (Day 1) up to Day 29 (end of treatment) |