Improvement In Scratch Behavior And Sleep In Patients With Atopic Dermatitis

Quantification of Improvement In Scratch Behavior And Sleep In Patients With Atopic Dermatitis on Crisaborole Ointment, 2%

This single blind study is to primarily evaluate wearable devices and Observer Reported Itch Assessment in children to assess reduction of itch and night-time scratch in response to Crisaborole treatment vs. vehicle treatment (active control comparator without crisaborole) in children with atopic dermatitis (AD). Participants, age 3 months to 11 years with symptomatic mild to moderate AD, along with their primary caregivers will be recruited.

The goal of this study is to more fully evaluate the rapid onset of night-time itch and scratch relief, as well as improvements in sleep following treatment with Crisaborole in comparison to vehicle treatment in children with AD. the study will also assess the quality of life (QoL) and sleep within the associated caregivers.

Approximately 270 children participants, age 3 months to ≤ 11 years, and their primary caregiver participants, for a total of 540 participants (270 pairs) will be randomized in 1:1 ratio to either Crisaborole (2% BID) or vehicle treatment and will be followed for 2 weeks. Participants will be asked to apply a thin even-layer of Crisaborole (2%) or vehicle twice daily (BID), excluding mouth, eyes, and vagina, per label, to all locations with active lesions (except for hands/fingers or within 1 to 2 fingers of the mouth to avoid inadvertent ingestion of ointment) and record location and time of application on the daily dosing form (provided by study staff, and as identified on the Dosing Record Sheet, breastfeeding women will be instructed to use the provided gloves when applying Crisaborole/vehicle). The study will be comprised of an initial screening/baseline visit for children participants who have an existing diagnosis of symptomatic AD, screened and enrolled in the study along with their primary caregivers after signing an informed consent (for parents/guardians and assent when appropriate).

Primary Objective:

1. Evaluate the effects of Crisaborole on itch and night-time scratch (as measured by accelerometry/actigraphy and Observer Reported Itch Assessment (3 months to ≤ 11 years old)) in children with mild to moderate AD between the ages of 3 months to ≤ 11 years old.

Secondary Objectives:

1. Evaluate the effects of Crisaborole on sleep in children ages 3 months to ≤ 11 years with mild to moderate AD.
2. Evaluate sleep in primary caregivers.
3. Evaluate the QoL measures in response to Crisaborole treatment (children 3 months to ≤ 11 years).
4. Evaluate QoL measures in response to the child's treatment, to the parents/caregivers/families.
5. Evaluate the effect of crisaborole treatment on AD signs, symptoms and severity in children ages 3 months to ≤ 11 years with mild to moderate AD.

The study will consist of a screening/baseline (in-laboratory) visit on Day -7 (V01), an in-laboratory visit Day 1 (V02), an in-laboratory visit on Day 2 (V03) for tape-striping, and Day 8 (V04) for a clinical assessment of the severity of the AD and a final in-laboratory visit on Day 15 (V05) for an assessment of the AD, tape-stripping, completion of ObsROs and return devices. Throughout the study, the participants and caregivers will wear accelerometry devices continuously (optional for those who have active AD on location of device placement, with a minimum of at least one wrist device needed for enrollment; devices may be removed for short periods of time for such things as the purposes of bathing, etc.). Enrolled participants will be randomly assigned to each arm of the study. Participants may come in for an unscheduled visit as needed (i.e., to replace compound, etc.). All in-person study activities, including informed consent and pregnancy testing, will be completed at the Laboratory for Human Neurobiology, 650 Albany St X140, Boston, MA, 02118. All activities performed in the laboratory are accomplished in private rooms. Primary caregivers will be provided with ample time and a privacy curtain to change into a gown during assessment for exclusion of Atopic Dermatitis, and primary caregivers will accompany children during all activities to ensure participant privacy. All at-home study activities will be completed in the participants' home.

Inclusion Criteria for Children (3 months to ≤ 11 years):

1. Male or female participants aged between ≥3 months of age and ≤ 11 years of age at Day -7.
2. Written informed consent from participant/parent(s)/guardian(s).
3. Native English speakers or demonstrated fluency in English (as age appropriate).
4. Participants and parent(s)/guardian(s) are willing and able to comply with study instructions, study visits, procedures, and device placement (devices will be optional for those who have active AD on location of device placement, with a minimum of at least one wrist device needed for enrollment).
5. Have a clinical diagnosis of AD according to the criteria of Hanifin and Rajka.
6. Have AD involvement ≥ 5% Treatable % Body Surface Area (BSA) excluding the scalp and less than 40% BSA.
7. Have an Investigator's Static Global Assessment (ISGA) score of Mild (2) or Moderate (3) at the baseline visit.
8. Have an Eczema Area and Severity Index (EASI) total score of ≥3 at Day -7.
9. Have a minimum Observer Reported Itch Assessment score of 2 at Day -7 (ages 3 months - ≤ 5 years only) or a minimum Patient Reported Itch Severity Scale score of 2 (ages 6 years - ≤ 11 years old) at Day -7.
10. Participant/parent(s)/guardian(s) agrees to refrain from applying diaper rash creams, lotions, ointments, powders, etc. where AD lesions are present, unless AD lesions are present where crisaborole cannot be applied (face within 1 or 2 fingers away from the mouth and hands/fingers).
11. Participants must agree to refrain from applying crisaborole/vehicle to AD lesions on the fingers or hands or within 1 or 2 fingers away from the the mouth to prevent inadvertent ingestion of ointment.

Inclusion Criteria for Adult Caregiver (18-75 years):

1. Primary caregiver of the enrolled child participant, between ≥18 years of age and ≤75 years of age.
2. Able to understand and cooperate with study procedures and give informed consent.
3. Native English speakers or demonstrated fluency in English
4. Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
5. ISGA score of 0 or 1 of AD at the screening visit, and no reported diagnosis of Atopic Dermatitis
6. WRAT-4 Word Reading Subtest equivalent to 8th grade reading level or greater.

Exclusion Criteria for Children:

1. Has any clinically significant medical disorder, condition, disease (including active or potentially recurrent non-AD dermatological conditions and known genetic dermatological conditions that overlap with AD, such as Netherton syndrome) or clinically significant finding at baseline that precludes participant's participation in study activities.
2. Participants who are on systemic corticosteroids or immunosuppressive agents within 28 days of Day -7 (V01).
3. 3. Participants who are on topical AD treatment such as low-to-high-potency corticosteroids, TCIs, antihistamines, antibiotics, sodium hypochlorite-based products, antibacterial soaps, bleach baths, diaper rash creams, lotions, ointments, powders, light therapy, and use of bland emollients on or overlapping with treatable AD-involved areas within 7 days of Day -7 (V01), unless AD lesions are present where crisaborole cannot be applied (face within 1 or 2 fingers away from the of mouth and hands/fingers).
4. Participants who are or have been on crisaborole treatment regimen in the past.
5. Allergy to polyurethane resin (strap/wristband component), skin nickel allergy, silicone, and/or adhesives.
6. Has documented non-AD related insomnia, sleep apnea or other sleep-related disorders (e.g., narcolepsy, restless legs syndrome, circadian rhythm disorder).
7. Participant has a known lack of efficacy to crisaborole.
8. Participant scores <20 on the Childhood Asthma Control Test (ages 4-≤ 11) indicating poorly controlled asthma.
9. If participant has a history of angioedema or anaphylaxis.
10. Has a significant active systemic or localized infection, including actively infected.
11. Has any planned surgical or medical procedure that would overlap with study participation.
12. Participants with cardiac pacemakers, electronic pumps or any other implanted medical devices.
13. Participants who are unable to wear at least one wrist device (one accelerometry device on at least one wrist).

Exclusion Criteria for Adult Caregiver:

1. Has any clinically significant medical disorder, condition, disease or clinically significant finding at screening that precludes Caregivers participation in study activities (e.g., sleep apnea, narcolepsy, etc.)
2. History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1drink=5ounces (150mL) wine, 12 ounces (360mL) of beer, or 1.5 ounces (45mL) of hard liquor) within 6 months of screening as disclosed by participant during evaluation.
3. Current shift worker or travel across more than two time zones in the past 2 weeks, and/or during the study period.
4. Has any planned surgical or medical procedure that would overlap with study participation.
5. Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are Boston University (BU)/Boston Medical Center (BMC) employees directly involved in the conduct of the study.
6. Allergy to polyurethane resin (strap/wristband component), skin nickel allergy, silicone, and/or adhesives.
7. A female who is pregnant.
8. The primary caregiver or share the same domicile of another child who has previously been or is currently enrolled in the study.