E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate and Severe Atopic Dermatitis |
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E.1.1.1 | Medical condition in easily understood language |
Atopic Dermatitis, also known as Atopic Eczema |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
To assess the efficacy and safety of upadacitinib combined with topical corticosteroids (TCS) for the treatment of adolescent and adult subjects with moderate to severe AD who are candidates for systemic therapy. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
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E.3 | Principal inclusion criteria |
• Male or female subjects 12-75 years of age • Active moderate to severe atopic dermatitis defined by EASI, IGA, BSA, and pruritus • Candidate for systemic therapy or have recently required systemic therapy for atopic dermatitis • Able to tolerate topical corticosteroids for atopic dermatitis lesions
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E.4 | Principal exclusion criteria |
• Prior exposure to any JAK inhibitor • Unable or unwilling to discontinue current AD treatments prior to the study • Requirement of prohibited medications during the study • Other active skin diseases or skin infections requiring systemic treatment or would interfere with appropriate assessment of atopic dermatitis lesions • Female subject who is pregnant, breastfeeding, or considering pregnancy during the study
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E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of subjects achieving validated IGA scale for Atopic Dermatitis (vIGA-AD) of 0 or 1 with at least two grades of reduction from baseline at Week 16; • Proportion of subjects achieving improvement from baseline of at least 75% on Eczema Area Severity Index (EASI 75) at Week 16. |
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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) |
The following key secondary endpoints will be analyzed to demonstrate superiority of each upadacitinib dose vs. placebo, unless otherwise specified. Key secondary endpoints for EU/EMA regulatory purposes are: • Proportion of subjects achieving an improvement (reduction) in Worst Pruritus Numerical Rating Scale (NRS) ≥ 4 from Baseline at Week 16 for subjects with Worst Pruritus NRS ≥ 4 at baseline; • Proportion of subjects achieving a 90% reduction in EASI (EASI 90) at Week 16; • Percent change from Baseline of Worst Pruritus NRS at Week 16; • Percent change in EASI score from Baseline at Week 16. • Proportion of subjects achieving an improvement (reduction) in Worst Pruritus NRS ≥ 4 from Baseline at Week 4 for subjects with Worst Pruritus NRS ≥ 4 at baseline; • Proportion of subjects achieving EASI 75 at Week 4; • Proportion of subjects achieving EASI 75 at Week 2; • Proportion of subjects achieving EASI 90 at Week 4; • Proportion of subjects achieving EASI 100 at Week 16 for 30 mg; • Proportion of subjects achieving vIGA-AD of 0 at Week 16 for 30 mg; • Proportion of subjects achieving an improvement (reduction) in Worst Pruritus NRS ≥ 4 from Baseline at Week 1 for subjects with Worst Pruritus NRS ≥ 4 at baseline.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 16 Week 16 Week 16 Week 16 Week 4 Week 4 Week 2 Week 4 Week 16 Week 1 |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 83 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
China |
Hong Kong |
Israel |
Japan |
New Zealand |
Puerto Rico |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |