E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012438 |
E.1.2 | Term | Dermatitis atopic |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | 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 patients with moderate to severe atopic dermatitis (AD) treated with dupilumab |
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E.2.2 | Secondary objectives of the trial |
- Evaluate changes in skin barrier function with TEWL assessed after STS in pre-defined lesional and non-lesional skin in patients with moderate to severe AD treated with dupilumab in reference to normal skin of healthy volunteers. - Evaluate time course of skin barrier function with TEWL assessed before and after STS in pre-defined lesional and non-lesional skin in patients with moderate to severe AD treated with dupilumab in reference to normal skin of healthy volunteers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant must be between 12 to 65 years of age (inclusive), at the time of signing the informed consent. Atopic dermatitis patients: - Male or female patients. - Patients with AD diagnosis according to Hanifin and Rajka criteria at least 1 year before screening. - IGA score of ≥3 at screening (on the 0-4 scale). - Patients with moderate to severe atopic dermatitis that are eligible to be treated with dupilumab according to product monograph - Patients with AD must have active lesions on the upper limbs or lower limbs, with severity for lesion erythema or edema/papulation ≥2 at screening on the 0-3 scale of the ISS. - Participants should have a non-lesional (normal looking) skin area 4 cm from the edge of the lesional area. If unable to identify non-lesional skin 4 cm from the lesional area, it is acceptable to identify normal looking skin as close to the lesion as possible. Healthy volunteers: - Age and gender matched to a selected AD patient. Adolescents aged 12 to 17 years will be matched by post puberty status, and adults aged 18 to 65 years will be matched by age as close as possible within 10 years of age.. |
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E.4 | Principal 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 (ie, skin atrophy, ichthyosis, Netherton syndrome, severe photo damage). - Cracked, crusted, oozing, or bleeding AD lesions in the designated lesional assessment area leaving insufficient skin that is adequate for TEWL assessments. - 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 dry eye syndrome that require daily use of supplemental lubrication; or individuals with ocular conditions that require the use of ocular corticosteroids or cyclosporine.
- Healthy volunteers with a personal history of an atopic condition. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change in TEWL after 5 STS on lesional skin in AD patients ; Percent change from baseline in TEWL after 5 STS assessed on lesional skin in AD patients |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1 - Percent change in TEWL after 20 STS on lesional skin in AD patients Absolute change in TEWL after 20 STS on lesional skin in AD patients 2 - Percent change in TEWL after 20 STS on non-lesional skin in AD patients Absolute change in TEWL after 20 STS on non-lesional skin in AD patients 3 - Percent change in TEWL after 20 STS on normal skin in healthy volunteers Absolute change in TEWL after 20 STS on normal skin in healthy volunteers 4 - Percent change in TEWL after 15 STS on lesional skin in AD patients Absolute change in TEWL after 15 STS on lesional skin in AD patients 5 - Percent change in TEWL after 15 STS on non-lesional skin in AD patients Absolute change in TEWL after 15 STS on non-lesional skin in AD patients 6 - Percent change in TEWL after 15 STS on normal skin in healthy volunteers Absolute change in TEWL after 15 STS on normal skin in healthy volunteers 7 - Percent change in TEWL after 10 STS on lesional skin in AD patients Absolute change in TEWL after 10 STS on lesional skin in AD patients 8 - Percent change in TEWL after 10 STS on non-lesional skin in AD patients Absolute change in TEWL after 10 STS on non-lesional skin in AD patients 9 - Percent change in TEWL after 10 STS on normal skin in healthy volunteers Absolute change in TEWL after 10 STS on normal skin in healthy volunteers 10 - Absolute change in TEWL after 5 STS on lesional skin in AD patients 11 - Percent change in TEWL after 5 STS on non-lesional skin in AD patients Absolute change in TEWL after 5 STS on non-lesional skin in AD patients 12 - Percent change in TEWL after 5 STS on normal skin in healthy volunteers Absolute change in TEWL after 5 STS on normal skin in healthy volunteers 13 - Percent change in TEWL before STS on lesional skin in AD patients over time Absolute change in TEWL before STS on lesional skin in AD patients over time 14 - Percent change in TEWL before STS on non-lesional skin in AD patients over time Absolute change in TEWL before STS on non-lesional skin in AD patients over time 15 - Percent change in TEWL before STS on normal skin in healthy volunteers over time Absolute change in TEWL before STS on normal skin in healthy volunteers over time 16 - Percent change in TEWL area under the curve (TEWL AUC: a composite measure before and after 5, 10, 15 and 20 STS) for skin barrier function in lesional skin in AD patients Absolute change in TEWL area under the curve (TEWL AUC: a composite measure before and after 5, 10, 15 and 20 STS) for skin barrier function in lesional skin in AD patients 17 - Percent change in TEWL AUC (a composite measure before and after 5, 10, 15, and 20 STS) for skin barrier function in non-lesional skin in AD patients Absolute change in TEWL AUC (a composite measure before and after 5, 10, 15, and 20 STS) for skin barrier function in non-lesional skin in AD patients 18 - Percent change in TEWL AUC (a composite measure before and after 5, 10, 15, and 20 STS) for skin barrier function in normal skin in healthy volunteers Absolute change in TEWL AUC (a composite measure before and after 5, 10, 15, and 20 STS) for skin barrier function in normal skin in healthy volunteers 19 - Percent change from baseline in TEWL after STS assessed on lesional skin in AD patients Absolute change from baseline in TEWL after STS assessed on lesional skin in AD patients 20 - Percent change from baseline in TEWL after STS assessed on non-lesional skin in AD patients Absolute change from baseline in TEWL after STS assessed on non-lesional skin in AD patients 21 - Percent change from baseline in TEWL after STS assessed on normal skin in healthy volunteers Absolute change from baseline in TEWL after STS assessed on normal skin in healthy volunteers |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 19 |