Dupilumab-PEdiatric Skin Barrier Function and LIpidomics STudy in Patients With Atopic Dermatitis

Sanofi41 enrolled

Overview

Primary Objective: \- Evaluate changes in skin barrier function with transepidermal water loss (TEWL) assessed after skin tape stripping (STS) in predefined lesional skin in pediatric participants with moderate to severe atopic dermatitis (AD) treated with dupilumab. Secondary Objectives: * Evaluate changes in skin barrier function with TEWL assessed after STS in predefined lesional and non-lesional skin in pediatric participants with moderate to severe AD treated with dupilumab in reference to normal skin of healthy volunteers. * Evaluate time course of change in skin barrier function with TEWL assessed before and after STS in predefined lesional and non-lesional skin in pediatric participants with moderate to severe AD during dupilumab treatment phase and follow-up period in reference to normal skin of healthy volunteers.

Total study duration including screening and follow-up was 32 weeks.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Dermatitis Atopic

Interventions

Eligibility

Sex: ALLMin age: 6 YearsMax age: 11 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria : * Participant must be between \>=6 to \<12 years of age (inclusive), at the time of signing the informed consent * 15 kg \<= body weight \<60 kg. Atopic dermatitis participants: * Male or female pediatric participants. * Participants with AD diagnosis according to Hanifin and Rajka criteria at least 1 year before screening. * Investigator Global Assessment (IGA) score of \>=3 (for US participants) or IGA \>=4 (for EU participants) at screening (on the 0-4 scale) depending on approved label indication in the country. * Participants with moderate to severe AD those were eligible to be treated with dupilumab according to product label. * Participants with AD must have had active lesions on the upper limbs or lower limbs (including trunk, if needed), with severity for lesion erythema or edema/papulation \>=2 at screening on the 0-3 scale of the Individual Signs Score. * Participants should have had a non-lesional (normal looking) skin area 4 centimeter (cm) from the edge of the lesional area. If unable to identify non-lesional skin 4 cm from the lesional area, it was acceptable to identify normal looking skin as close to the lesion as possible. Healthy volunteers: \- Age and gender matched (match on age ±2 years) to a selected AD participant by study site. Exclusion criteria: * Previous treatment with dupilumab within 6 months prior to screening. * Skin conditions other than AD that can confound assessments in the area of TEWL assessments in the opinion of the Investigator (i.e., skin atrophy, ichthyosis, tinea infection, contact dermatitis). * Cracked, crusted, oozing, or bleeding AD lesions in the designated lesional assessment area leaving insufficient skin that was adequate for TEWL assessments. * Hypersensitivity to the active substance or to any of the excipients of dupilumab. * Ocular disorder that in the opinion of the Investigator could adversely affect the individual's risk for study participation. Examples include -but are not limited to- individuals with a history of active cases of herpes keratitis; Sjogren's syndrome, keratoconjunctivitis sicca, or individuals with ocular conditions that require the use of ocular corticosteroids or cyclosporine. * Healthy volunteers with a personal history of an atopic condition. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Locations (3)

Investigational Site Number :8400002

Los Angeles, California, United States

Investigational Site Number :8400001

Denver, Colorado, United States

Investigational Site Number :8260001

Sheffield, United Kingdom

Outcomes

Primary Outcomes

Percent Change From Baseline in Transepidermal Water Loss (TEWL) After 5 Skin Tape Stripping (STS) on Lesional Skin (LS) in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize skin barrier function (SBF). TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. Lesional skin (LS) areas for TEWL assessment and STS was identified at Baseline ('predefined skin area'). Within the predefined LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined LS areas at specified time points. STS assessment at Baseline (Week 0, Day 1) and Week 16 was conducted on the first spot. Percent Change from Baseline at Week 16 in TEWL after 5 STS on LS (first spot) in AD participants were reported in this outcome measure (OM).

Time frame: Baseline, Week 16

Secondary Outcomes

Percent Change From Baseline in TEWL After 20 STS on Lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS areas for TEWL assessment and STS were identified at Baseline (predefined skin area). Within the predefined LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined LS areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from baseline at Week 16 in TEWL after 20 STS on LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 20 STS on Lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that was used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined LS areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Absolute change from Baseline at Week 16 in TEWL after 20 STS on LS (first spot) in AD participants were reported in this OM

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL After 20 STS on Non-lesional Skin (Non-LS) in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The non-LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined non-LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined non-LS areas at specified time points. STS assessment at Baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from Baseline at Week 16 in TEWL after 20 STS on non-LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 20 STS on Non-lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The non-LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined non-LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined non-LS areas at specified time points. STS assessment at Baseline (Week 0, Day 1) and Week 16 was conducted on the first spot. Absolute change from baseline at Week 16 in TEWL after 20 STS on non-LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL After 20 STS on Normal Skin in Healthy Volunteers at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The normal skin areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined normal skin areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined normal skin areas at specified time points. STS assessment at Baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from baseline at Week 16 in TEWL after 20 STS on normal skin (first spot) in healthy volunteers were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 20 STS on Normal Skin in Healthy Volunteers at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The normal skin areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined normal skin areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined normal skin areas at specified time points. STS assessment at Baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Absolute change from baseline at Week 16 in TEWL after 20 STS on normal skin (first spot) in healthy volunteers were reported in this OM.

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL After 15 STS on Lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined LS and non-LS areas at specified time points. STS assessment at Baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from baseline at Week 16 in TEWL after 15 STS on LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 15 STS on Lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined LS areas at specified time points. STS assessment at Baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Absolute change from baseline at Week 16 in TEWL after 15 STS on LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL After 15 STS on Non-lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The non-LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined non-LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined non-LS areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from baseline at Week 16 in TEWL after 15 STS on non-LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 15 STS on Non-lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The non-LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined non-LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined non-LS areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Absolute change from baseline at Week 16 in TEWL after 15 STS on non-LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL After 15 STS on Normal Skin in Healthy Volunteers at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The normal skin areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined normal skin areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined normal skin areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from baseline at Week 16 in TEWL after 15 STS on normal skin (first spot) in healthy volunteers were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 15 STS on Normal Skin in Healthy Volunteers at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The normal skin areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined normal skin areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined normal skin areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Absolute change from baseline at Week 16 in TEWL after 15 STS on normal skin (first spot) in healthy volunteers were reported in this OM.

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL After 10 STS on Lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined LS areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from baseline at Week 16 in TEWL after 10 STS on LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 10 STS on Lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined LS areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Absolute change from baseline at Week 16 in TEWL after 10 STS on LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL After 10 STS on Non-lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The non-LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined non-LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined non-LS areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from baseline at Week 16 in TEWL after 10 STS on non-LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 10 STS on Non-lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The non-LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined non-LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined non-LS areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Absolute change from baseline at Week 16 in TEWL after 10 STS on non-LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL After 10 STS on Normal Skin in Healthy Volunteers at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The normal skin areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined normal skin areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined normal skin areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from baseline at Week 16 in TEWL after 10 STS on normal skin (first spot) in healthy volunteers were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 10 STS on Normal Skin in Healthy Volunteers at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The normal skin areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined normal skin areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined normal skin areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Absolute change from baseline at Week 16 in TEWL after 10 STS on normal skin (first spot) in healthy volunteers were reported in this OM.

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL After 5 STS on Non-lesional Skin in AD Participants at Week16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The non-LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined non-LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined non-LS areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from baseline at Week 16 in TEWL after 5 STS on non-LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 5 STS on Non-lesional Skin in AD Participants at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The non-LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined non-LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined non-LS areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Absolute change from baseline at Week 16 in TEWL after 5 STS on non-LS (first spot) in AD participants were reported in this OM.

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL After 5 STS on Normal Skin in Healthy Volunteers at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The normal skin areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined normal skin areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined normal skin areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Percent change from baseline at Week 16 in TEWL after 5 STS on normal skin (first spot) in healthy volunteers were reported in this OM.

Time frame: Baseline, Week 16

Absolute Change From Baseline in TEWL After 5 STS on Normal Skin in Healthy Volunteers at Week 16

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The normal skin areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined normal skin areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined normal skin areas at specified time points. STS assessment at baseline (Week 0, Day 1) and Week 16 was conducted on first spot. Absolute change from baseline at Week 16 in TEWL after 5 STS on normal skin (first spot) in healthy volunteers were reported in this OM.

Time frame: Baseline, Week 16

Percent Change From Baseline in TEWL Before STS on Lesional Skin in AD Participants at Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. LS areas for TEWL assessment were identified at baseline ('predefined skin area'). Within predefined LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS on pre-defined LS areas at specified time points. At each visit, before STS, all three spots were assessed. Percent change from Baseline at specified time points in TEWL before STS on LS (at each spot) in AD participants were reported in this OM.

Time frame: Baseline, Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

Absolute Change From Baseline in TEWL Before STS on Lesional Skin in AD Participants at Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. LS areas for TEWL assessment were identified at baseline (predefined skin area). Within predefined LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS on pre-defined LS areas at specified time points. At each visit, before STS, all three spots were assessed. Absolute change from baseline at specified time points in TEWL before STS on LS (at each spot) in AD participants were reported in this OM.

Time frame: Baseline, Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

Percent Change From Baseline in TEWL Before STS on Non-lesional Skin in AD Participants at Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. Non-LS areas for TEWL assessment were identified at baseline (predefined skin area). Within predefined non-LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS on pre-defined non-LS areas at specified time points. At each visit, before STS, all three spots were assessed. Percent change from baseline at specified time points in TEWL before STS on non-LS (at each spot) in AD participants were reported in this OM.

Time frame: Baseline, Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

Absolute Change From Baseline in TEWL Before STS on Non-lesional Skin in AD Participants at Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. Non-LS areas for TEWL assessment were identified at baseline (predefined skin area). Within predefined non-LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS on pre-defined non-LS areas at specified time points. At each visit, before STS, all three spots were assessed. Absolute change from baseline at specified time points in TEWL before STS on non-LS (at each spot) in AD participants were reported in this OM.

Time frame: Baseline, Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

Percent Change From Baseline in TEWL Before STS on Normal Skin in Healthy Volunteers at Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. Normal skin areas for TEWL assessment were identified at baseline (predefined skin area). Within predefined normal skin areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS on pre-defined normal skin areas at specified time points. At each visit, before STS, all three spots were assessed. Percent change from Baseline at specified time points in TEWL before STS on normal skin (at each spot) in healthy volunteers were reported in this OM.

Time frame: Baseline, Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

Absolute Change From Baseline in TEWL Before STS on Normal Skin in Healthy Volunteers at Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. Normal skin areas for TEWL assessment were identified at baseline (predefined skin area). Within predefined normal skin areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS on pre-defined normal skin areas at specified time points. At each visit, before STS, all three spots were assessed. Absolute change from baseline at specified time points in TEWL before STS on normal skin (at each spot) in healthy volunteers were reported in this OM.

Time frame: Baseline, Days 8, 15, 22, 29, 43, 57, 85, 113, 155 and 197

Percent Change From Baseline in Area Under the Curve (AUC) of TEWL on Lesional Skin in AD Participants at Days 57, 113 and 197

TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterize SBF. TEWL combined with STS measures SBF. TEWL AUC done over defined number of STS was used to reflect the overall integrity of the stratum corneum. LS areas for TEWL assessment and STS were identified at baseline (predefined skin area). Within the predefined LS areas, 3 closely adjacent non-overlapping spots were identified for subsequent SBF assessment. TEWL was measured prior to STS and after 5, 10, 15 and 20 STS on pre-defined LS areas at specified time points. TEWL AUC was a composite measure before and after 5, 10, 15 and 20 STS at each specified time point. AUC of TEWL: calculated for each visit using trapezoidal method. STS assessment at baseline (Week 0, Day 1), Days 57, 113 and 197 was conducted on first spot. Percent change from baseline at specified time points in TEWL AUC (first spot) in AD participants were reported in this OM.