Clinical Trial Results:
Open Label Exploratory Study to Evaluate the Effect of Dupilumab on Skin Barrier Function in Patients With Moderate to Severe Atopic Dermatitis
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Summary
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EudraCT number |
2020-000314-15 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
17 Jun 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Jan 2022
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First version publication date |
11 Jan 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
LPS15991
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04447417 | ||
WHO universal trial number (UTN) |
U1111-1244-1409 | ||
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Sponsors
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Sponsor organisation name |
Sanofi-aventis Recherche & Développement
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Sponsor organisation address |
1 avenue Pierre Brossolette, Chilly-Mazarin Cedex, France, 91380
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Jul 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Jun 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluate changes in skin barrier function with transepidermal water loss (TEWL) assessed after skin tape stripping (STS) in pre-defined lesional skin in subjects with moderate to severe atopic dermatitis (AD) treated with dupilumab.
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Protection of trial subjects |
The study was conducted by investigators experienced in the treatment of adults and paediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimised. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimise distress and discomfort. Adult subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Jul 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 16
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Country: Number of subjects enrolled |
Canada: 36
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Worldwide total number of subjects |
52
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
12
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Adults (18-64 years) |
40
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Study was conducted at 2 centers in the United States and Canada. A total of 52 eligible subjects were enrolled between 16 July 2020 and 19 January 2021 under the AD subjects cohort or the healthy volunteers cohort. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Healthy volunteer’s cohort received no treatment and was considered as a reference comparator group. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Healthy Volunteer | |||||||||||||||||||||
Arm description |
Healthy volunteers with age, gender, location of targeted skin lesion area and study site matched to a selected atopic dermatitis (AD) subjects, received no treatment, but were monitored in similar way as AD subjects. | |||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Atopic Dermatitis Patients | |||||||||||||||||||||
Arm description |
Subjects with moderate to severe AD and aged 18 years and older received dupilumab 600 milligrams (mg) (loading dose) subcutaneous (SC) injection on Day 1, followed by dupilumab 300 mg SC injection every 2 weeks (Q2W) through Week 14 (i.e., at Day 15, 29, 43, 57 and 85). Subjects aged greater than or equal to (>=) 12 to less than (<) 18 years received treatment based on their body weight: <60 kilograms (kg) and >=60 kg - received dupilumab 400 mg and 600 mg (loading dose) SC injection on Day 1, respectively, followed by dupilumab 200 mg and 300 mg SC injection Q2W through Week 14 (i.e., at Day 15, 29, 43, 57 and 85). | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Dupilumab
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Investigational medicinal product code |
SAR231893
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Other name |
Dupixent®/REGN668
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Dupilumab loading dose 600 mg and 400 mg as SC injections, respectively on Day 1. Subsequent doses of dupilumab 200 mg and 300 mg SC injection Q2W through Week 14 (i.e., at Day 15, 29, 43, 57 and 85).
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Baseline characteristics reporting groups
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Reporting group title |
Healthy Volunteer
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Reporting group description |
Healthy volunteers with age, gender, location of targeted skin lesion area and study site matched to a selected atopic dermatitis (AD) subjects, received no treatment, but were monitored in similar way as AD subjects. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Atopic Dermatitis Patients
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Reporting group description |
Subjects with moderate to severe AD and aged 18 years and older received dupilumab 600 milligrams (mg) (loading dose) subcutaneous (SC) injection on Day 1, followed by dupilumab 300 mg SC injection every 2 weeks (Q2W) through Week 14 (i.e., at Day 15, 29, 43, 57 and 85). Subjects aged greater than or equal to (>=) 12 to less than (<) 18 years received treatment based on their body weight: <60 kilograms (kg) and >=60 kg - received dupilumab 400 mg and 600 mg (loading dose) SC injection on Day 1, respectively, followed by dupilumab 200 mg and 300 mg SC injection Q2W through Week 14 (i.e., at Day 15, 29, 43, 57 and 85). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Healthy Volunteer
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Reporting group description |
Healthy volunteers with age, gender, location of targeted skin lesion area and study site matched to a selected atopic dermatitis (AD) subjects, received no treatment, but were monitored in similar way as AD subjects. | ||
Reporting group title |
Atopic Dermatitis Patients
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Reporting group description |
Subjects with moderate to severe AD and aged 18 years and older received dupilumab 600 milligrams (mg) (loading dose) subcutaneous (SC) injection on Day 1, followed by dupilumab 300 mg SC injection every 2 weeks (Q2W) through Week 14 (i.e., at Day 15, 29, 43, 57 and 85). Subjects aged greater than or equal to (>=) 12 to less than (<) 18 years received treatment based on their body weight: <60 kilograms (kg) and >=60 kg - received dupilumab 400 mg and 600 mg (loading dose) SC injection on Day 1, respectively, followed by dupilumab 200 mg and 300 mg SC injection Q2W through Week 14 (i.e., at Day 15, 29, 43, 57 and 85). | ||
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End point title |
Percent Change From Baseline in Transepidermal Water Loss After 5 Skin Tape Stripping on Lesional Skin (LS) in AD Patients at Week 16 [1] [2] | ||||||||
End point description |
TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise skin barrier function (SBF). TEWL combined with STS measures SBF. With STS, the uppermost layers of skin are peeled away using adhesive discs. LS areas for TEWL assessment and STS was identified at Baseline (predefined skin area). Within predefined LS areas, 3 closely adjacent non-overlapping spots 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 1st spot. Percent Change from Baseline at Week 16 in TEWL after 5 STS on LS (1st spot) in AD subjects were reported in this endpoint. mITT:AD subjects, had at least 1 dose of IMP and healthy volunteers, had at least 1 TEWL/STS. If prohibited therapies used, only visits prior to rescue therapy were considered. Number of subjects analysed=subjects evaluable.
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End point type |
Primary
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End point timeframe |
Baseline, Week 16
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As the end-point was descriptive in nature no statistical analysis was provided. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent Change From Baseline in TEWL After 20 STS on Lesional and Non-lesional Skin (Non-LS) in AD Patients at Week 16 [3] | ||||||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS and non-LS areas for TEWL assessment and STS were identified at Baseline ('predefined skin area'). Within the predefined LS and non-LS areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment (3 spots on LS, 3 spots on non-LS). 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 20 STS on LS and non-LS (1st spot) in AD subjects were reported in this endpoint. Analysed on modified intent-to-treat (mITT) population. Here, 'n' = subjects with available data for each specified category.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Absolute Change in TEWL After 20 STS on Lesional and Non-lesional Skin in AD Patients at Week 16 [4] | ||||||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS and non-LS areas for TEWL assessment and STS were identified at Baseline ('predefined skin area'). Within the predefined LS and non-LS areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment (3 spots on LS, 3 spots on non-LS). 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. Absolute change from Baseline at Week 16 in TEWL after 20 STS on LS and non-LS (first spot) in AD subjects were reported in this endpoint. Analysis was performed on mITT population. Here, 'n'=subjects with available data for each specified category.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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| Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percent Change From Baseline in TEWL After 20 STS on Normal Skin in Healthy Volunteers at Week 16 [5] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Absolute Change From Baseline in TEWL After 20 STS on Normal Skin in Healthy Volunteers at Week 16 [6] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent Change From Baseline in TEWL After 15 STS on Lesional and Non-lesional Skin in AD Patients at Week 16 [7] | ||||||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS and non-LS areas for TEWL assessment and STS were identified at Baseline ('predefined skin area'). Within the predefined LS and non-LS areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment (3 spots on LS, 3 spots on non-LS). 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 and non-LS (first spot) in AD subjects were reported in this endpoint. Analysis was performed on mITT population. Here, 'n'=subjects with available data for each specified category.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Absolute Change From Baseline in TEWL After 15 STS on Lesional and Non-lesional Skin in AD Patients at Week 16 [8] | ||||||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS and non-LS areas for TEWL assessment and STS were identified at Baseline ('predefined skin area'). Within the predefined LS and non-LS areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment (3 spots on LS, 3 spots on non-LS). 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. Absolute change from Baseline at Week 16 in TEWL after 15 STS on LS and non-LS (first spot) in AD subjects were reported in this endpoint. Analysis was performed on mITT population. Here, 'n'=subjects with available data for each specified category.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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| Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percent Change From Baseline in TEWL After 15 STS on Normal Skin in Healthy Volunteers at Week 16 [9] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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| Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Absolute Change From Baseline in TEWL After 15 STS on Normal Skin in Healthy Volunteers at Week 16 [10] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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| Notes [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent Change From Baseline in TEWL After 10 STS on Lesional and Non-lesional Skin in AD Patients at Week 16 [11] | ||||||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS and non-LS areas for TEWL assessment and STS were identified at Baseline ('predefined skin area'). Within the predefined LS and non-LS areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment (3 spots on LS, 3 spots on non-LS). 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 10 STS on LS and non-LS (first spot) in AD subjects were reported in this endpoint. Analysis was performed on mITT population. Here, 'n'=subjects with available data for each specified category.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
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| Notes [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Absolute Change From Baseline in TEWL After 10 STS on Lesional and Non-lesional Skin in AD Patients at Week 16 [12] | ||||||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. TEWL combined with STS measures SBF. With STS, the uppermost layers of the skin are peeled away using adhesive discs. The LS and non-LS areas for TEWL assessment and STS were identified at Baseline ('predefined skin area'). Within the predefined LS and non-LS areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment (3 spots on LS, 3 spots on non-LS). 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. Absolute change from Baseline at Week 16 in TEWL after 10 STS on LS and non-LS (first spot) in AD subjects were reported in this endpoint. Anlysis was performed on mITT population. Here, 'n'=subjects with available data for each specified category.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 16
|
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| Notes [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Absolute Change From Baseline in TEWL After 10 STS on Normal Skin in Healthy Volunteers at Week 16 [13] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 16
|
||||||||
| Notes [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percent Change From Baseline in TEWL After 10 STS on Normal Skin in Healthy Volunteers at Week 16 [14] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 16
|
||||||||
| Notes [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percent Change From Baseline in TEWL After 5 STS on Non-lesional Skin in AD Patients at Week 16 [15] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 subjects were reported in this endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 16
|
||||||||
| Notes [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change From Baseline in TEWL After 5 STS on Lesional Skin in AD Patients at Week 16 [16] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 5 STS on LS (first spot) in AD subjects were reported in this endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 16
|
||||||||
| Notes [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change From Baseline in TEWL After 5 STS on Non-lesional Skin in AD Patients at Week 16 [17] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 subjects were reported in this endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 16
|
||||||||
| Notes [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Absolute Change From Baseline in TEWL After 5 STS on Normal Skin in Healthy Volunteers at Week 16 [18] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 16
|
||||||||
| Notes [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percent Change From Baseline in TEWL After 5 STS on Normal Skin in Healthy Volunteers at Week 16 [19] | ||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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 endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline, Week 16
|
||||||||
| Notes [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percent Change From Baseline in TEWL Before STS on Lesional and Non-lesional Skin in AD Patients at Day 4, 8, 11, 15, 22, 29, 43, 57, 85 and Week 16 [20] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. LS and non-LS areas for TEWL assessment were identified at Baseline ('predefined skin area'). Within predefined LS and non-LS areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment (3 spots on LS, 3 spots on non-LS). TEWL was measured prior to STS on pre-defined LS and non-LS areas at specified time points. At each visit, before STS, all three spots were assessed, and their value was averaged to derive a single value. Percent change from Baseline at specified time points in TEWL before STS on LS and non-LS in AD subjects were reported in this endpoint. Analysis was performed on mITT population. Here, 'n' = subjects with available data for each specified category.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Day 4, 8, 11, 15, 22, 29, 43, 57, 85 and Week 16
|
||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Absolute Change From Baseline up to Week 16 in TEWL Before STS on Lesional and Non-lesional Skin in AD Patients at Day 4, 8, 11, 15, 22, 29, 43, 57, 85 and Week 16 [21] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. LS and non-LS areas for TEWL assessment were identified at Baseline ('predefined skin area'). Within predefined LS and non-LS areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment (3 spots on LS, 3 spots on non-LS). TEWL was measured prior to STS on pre-defined LS and non-LS areas at specified time points. At each visit, before STS, all three spots were assessed, and their value was averaged to derive a single value. Absolute change from Baseline at specified time points in TEWL before STS on LS and non-LS in AD subjects were reported in this endpoint. Analysis was performed on mITT population. Here, 'n' = subjects with available data for each specified category.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Day 4, 8, 11, 15, 22, 29, 43, 57, 85 and Week 16
|
||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Percent Change From Baseline in TEWL Before STS on Normal Skin in Healthy Volunteers at Day 4, 8, 11, 15, 22, 29, 43, 57, 85 and Week 16 [22] | ||||||||||||||||||||||||||||
End point description |
TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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, and their value was averaged to derive a single value. Percent change from Baseline at specified time points in TEWL before STS on normal skin in healthy volunteers were reported in this endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint and 'n' = subjects with available data for each specified category.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Baseline, Day 4, 8, 11, 15, 22, 29, 43, 57, 85 and Week 16
|
||||||||||||||||||||||||||||
| Notes [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
|||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Absolute Change From Baseline in TEWL Before STS on Normal Skin in Healthy Volunteers at Day 4, 8, 11, 15, 22, 29, 43, 57, 85 and Week 16 [23] | ||||||||||||||||||||||||||||
End point description |
TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 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, and their value was averaged to derive a single value. Absolute change from Baseline at specified time points in TEWL before STS on normal skin in healthy volunteers were reported in this endpoint. Analysis was performed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint and 'n' = subjects with available data for each specified category.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Baseline, Day 4, 8, 11, 15, 22, 29, 43, 57, 85 and Week 16
|
||||||||||||||||||||||||||||
| Notes [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
|||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percent Change From Baseline in TEWL After 5, 10, 15 and 20 STS on Lesional and Non-lesional Skin in AD Patients at Day 15, 29, 57, 85 and Week 16 [24] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. TEWL combined with STS measures SBF. With STS, uppermost layers of skin are peeled away using adhesive discs. LS and non-LS areas for TEWL assessment and STS were identified at Baseline ('predefined skin area'). Within predefined LS and non-LS areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment(3 spots on LS, 3 spots on non-LS). TEWL: 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 was done at Baseline (Week 0, Day 1), Day 57 and Week 16 on 1st spot; at Day 15 on 2nd spot and at Day 29 and Day 85 on 3rd spot. Percent change from Baseline at specified time points in TEWL after STS on LS and non-LS in AD subjects were reported in this endpoint. mITT population. Here, 'n' = subjects with available data.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Day 15, 29, 57, 85 and Week 16
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Absolute Change From Baseline in TEWL After 5, 10, 15 and 20 STS on Lesional and Non-lesional Skin in AD Patients at Day 15, 29, 57, 85 and Week 16 [25] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. TEWL combined with STS measures SBF. With STS, uppermost layers of skin are peeled away using adhesive discs. LS and non-LS areas for TEWL assessment and STS were identified at Baseline ('predefined skin area'). Within predefined LS and non-LS areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment(3 spots on LS, 3 spots on non-LS). TEWL: 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 was done at Baseline (Week 0, Day 1), Day 57 and Week 16 on 1st spot; at Day 15 on 2nd spot and at Day 29 and Day 85 on 3rd spot. Absolute change from Baseline at specified time points in TEWL after STS on LS and non-LS in AD subjects were reported in this endpoint. mITT population. Here, 'n'=subjects with available data for each specified category.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Day 15, 29, 57, 85 and Week 16
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percent Change From Baseline in TEWL After 5, 10, 15 and 20 STS on Normal Skin in Healthy Volunteers at Day 15, 29, 57, 85 and Week 16 [26] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. TEWL combined with STS measures SBF. With STS, uppermost layers of skin are peeled away using adhesive discs. Normal skin areas for TEWL assessment and STS were identified at Baseline ('predefined skin area'). Within predefined normal skin areas, 3 closely adjacent non-overlapping spots 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 was done at Baseline (Week 0, Day 1), Day 57 and Week 16 on 1st spot; at Day 15 on 2nd spot and at Day 29 and Day 85 on 3rd spot. Percent change from Baseline at specified time points in TEWL after STS on normal skin in healthy volunteers were reported in this endpoint. mITT population. Here, number of subjects analysed=subjects evaluable and 'n'=subjects with data a for each specified category.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Day 15, 29, 57, 85 and Week 16
|
||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Absolute Change From Baseline in TEWL After 5, 10, 15 and 20 STS on Normal Skin in Healthy Volunteers at Day 15, 29, 57, 85 and Week 16 [27] | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise SBF. TEWL combined with STS measures SBF. With STS, uppermost layers of skin are peeled away using adhesive discs. Normal skin areas for TEWL assessment and STS were identified at Baseline ('predefined skin area'). Within predefined normal skin areas, 3 closely adjacent non-overlapping spots 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 was done at Baseline (Week 0, Day 1), Day 57 and Week 16 on 1st spot; at Day 15 on 2nd spot and at Day 29 and Day 85 on 3rd spot. Absolute change from Baseline at specified time points in TEWL after STS on normal skin in healthy volunteers were reported in this endpoint. mITT population. Here, number of subjects analysed=subjects evaluable and 'n'=subjects with data a for each specified category.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Day 15, 29, 57, 85 and Week 16
|
||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Percent Change From Baseline in Area Under the Curve (AUC) of TEWL on Lesional and Non-lesional Skin in AD Patients at Day 15, 29, 57, 85 and Week 16 [28] | ||||||||||||||||||||||||||||
End point description |
TEWL assessment: noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 and non-LS areas for TEWL assessment and STS was identified at Baseline ('predefined skin area'). Within the predefined LS and non-LS areas, 3 closely adjacent nonoverlapping spots identified for subsequent SBF assessment (3 spots on LS, 3 spots on non-LS). 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. 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 rule. Percent change from Baseline at specified time points in TEWL AUC in AD subjects were reported in this endpoint. mITT population. Here, 'n'=subjects with available data for each category.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 15, 29, 57, 85 and Week 16
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| Notes [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Absolute Change From Baseline in Area Under the Curve of TEWL on Lesional and Non-lesional Skin in AD Patients at Day 15, 29, 57, 85 and Week 16 [29] | ||||||||||||||||||||||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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 and non-LS areas for TEWL assessment and STS was identified at Baseline ('predefined skin area'). Within the predefined LS and non-LS areas, 3 closely adjacent nonoverlapping spots identified for subsequent SBF assessment (3 spots on LS, 3 spots on non-LS). 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. 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 rule. Absolute change from Baseline at specified time points in TEWL AUC in AD subjects were reported in this endpoint. Analysed on mITT population. Here, 'n'=subjects with available data.
|
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End point type |
Secondary
|
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End point timeframe |
Baseline, Day 15, 29, 57, 85 and Week 16
|
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| Notes [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Healthy Volunteer arm as pre-specified in protocol. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
|
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End point title |
Percent Change From Baseline in Area Under the Curve of TEWL on Normal Skin in Healthy Volunteers at Day 15, 29, 57, 85 and Week 16 [30] | ||||||||||||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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. Normal skin areas for TEWL assessment and STS was identified at Baseline ('predefined skin area'). Within the predefined normal skin areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment. TEWL measured prior to STS and after 5,10,15 and 20 STS on pre-defined normal skin 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 rule. Percent Change from Baseline at specified time points in TEWL AUC in healthy volunteers were reported in this endpoint. Analysed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
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End point type |
Secondary
|
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End point timeframe |
Baseline, Day 15, 29, 57, 85 and Week 16
|
||||||||||||||||||
| Notes [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
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| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Absolute Change From Baseline in TEWL Area Under the Curve (AUC) on Normal Skin in Healthy Volunteers at Day 15, 29, 57, 85 and Week 16 [31] | ||||||||||||||||||
End point description |
TEWL assessment: a noninvasive in vivo measurement of water loss across stratum corneum that is used to characterise 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. Normal skin areas for TEWL assessment and STS was identified at Baseline ('predefined skin area'). Within the predefined normal skin areas, 3 closely adjacent non-overlapping spots identified for subsequent SBF assessment. TEWL measured prior to STS and after 5,10,15 and 20 STS on pre-defined normal skin 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 rule. Absolute change from Baseline at specified time points in TEWL AUC in healthy volunteers were reported in this endpoint. Analysed on mITT population. Here, number of subjects analysed = subjects evaluable for this endpoint.
|
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End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Day 15, 29, 57, 85 and Week 16
|
||||||||||||||||||
| Notes [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Data for this endpoint was not planned to be collected and analysed for Atopic Dermatitis Patients arm as pre-specified in the protocol. |
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
For AD subjects: from first dose (i.e., Day 1) of IMP administration up to end of treatment visit (i.e., Day 113). For healthy volunteers: from signature of consent form to end of study (i.e., from screening to Day 141)
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Adverse event reporting additional description |
Reported adverse events (AEs) and deaths were treatment-emergent AEs (TEAEs) that occurred, worsened or became serious during TEAE period of AD subjects (defined as time from 1st IMP administration to end of treatment) and for healthy volunteers: from signature of consent form to end of study. Analysis was performed on safety population.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Atopic Dermatitis Patients
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Reporting group description |
Subjects with moderate to severe AD and aged 18 years and older received dupilumab 600 milligrams (mg) (loading dose) subcutaneous (SC) injection on Day 1, followed by dupilumab 300 mg SC injection every 2 weeks (Q2W) through Week 14 (i.e., at Day 15, 29, 43, 57 and 85). Subjects aged greater than or equal to (>=) 12 to less than (<) 18 years received treatment based on their body weight: <60 kilograms (kg) and >=60 kg - received dupilumab 400 mg and 600 mg (loading dose) SC injection on Day 1, respectively, followed by dupilumab 200 mg and 300 mg SC injection Q2W through Week 14 (i.e., at Day 15, 29, 43, 57 and 85). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Healthy volunteer
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Reporting group description |
Healthy volunteers with age, gender, location of targeted skin lesion area and study site matched to a selected atopic dermatitis (AD) subjects, received no treatment, but were monitored in similar way as AD subjects. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
28 Jul 2020 |
The following changes were done:
• To further characterise the treatment effect of dupilumab in adolescent and adult subjects with moderate to severe AD in reference to matched healthy controls, a proteomics assessment and a transcriptomics assessment from skin tape strips were added.
• These assessments allowed for better assessment of the mechanism of dupilumab in AD. To have comparable data in lesional skin and nonlesional skin of AD subjects as well as in normal skin of healthy volunteers, the number of skin tape strips collected was set to 20
for each skin area.
• In response to the global COVID-19 pandemic, benefit-risk assessment in the context of COVID-19 was introduced. Implementation of temporary or alternative mechanisms such as phone contact, virtual visits, online meetings, use of local clinic or laboratory locations, and home visits by skilled staff (as permitted per local regulations) were allowed to ensure the study continuity and protect subjects’ safety. No waivers to deviate from protocol enrollment criteria due to COVID‑19 were granted. Remote monitoring was implemented when onsite monitoring was not allowed. All temporary mechanisms utilised and deviations from planned study procedures were documented as being related to the COVID-19 pandemic. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
