E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Atopic Dermatitis |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to Severe Atopic Dermatitis |
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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 |
1. Sub-Study 1 (SS1): The primary study objective for SS1 is to evaluate the efficacy and safety of dose escalation to upadacitinib 30 mg QD in subjects who do not achieve Eczema Area and Severity Index (EASI) 90 on upadacitinib 15 mg QD after 12 weeks. 2. Sub-Study 2 (SS2): The primary study objective for SS2 is to evaluate the efficacy and safety of dose reduction to upadacitinib 15 mg QD in subjects who achieve EASI 90 on upadacitinib 30 mg QD after 12 weeks. No hypothesis testing will be performed in this study. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female subjects ≥18 and < 65 years of age at the Screening Visit • Chronic AD with onset of symptoms at least 3 years prior to Baseline and subject meets Hanifin and Rajka criteria • Candidate for systemic treatment |
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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 treatment • 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) |
The primary endpoints is: Achievement of EASI 90 at Week 24.
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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 secondary endpoints are: 1. Achievement of EASI 75 / 100 at Week 24. 2. Achievement of EASI 75 / 90 / 100 at Week 12. 3. Achievement of EASI 90 and a Worst Pruritus NRS of 0 or 1 for subjects with Worst Pruritus NRS > 1 at Baseline at Week 12 and Week 24. 4. Achievement of a vIGA-AD of 0 or 1 at Week 12. 5. Achievement of vIGA-AD of 0 or 1 at Week 24. 6. Achievement of an improvement (reduction) in Worst Pruritus NRS ≥ 4 for subjects with Worst Pruritus NRS ≥ 4 at Baseline at Week 12. 7. Achievement of an improvement (reduction) in Worst Pruritus NRS ≥ 4 for subjects with Worst Pruritus NRS ≥ 4 at Baseline at Week 24. 8. Achievement of Worst Pruritus NRS of 0 or 1 for subjects with Worst Pruritus NRS > 1 at Baseline at Week 12. 9. Achievement of Worst Pruritus NRS of 0 or 1 for subjects with Worst Pruritus NRS > 1 at Baseline at Week 24. 10. Achievement of an improvement (reduction) from Baseline in DLQI ≥ 4 for subjects with DLQI ≥ 4 at Baseline at Week 12. 11. Achievement of an improvement (reduction) from Baseline in DLQI ≥ 4 for subjects with DLQI ≥ 4 at Baseline at Week 24. 12. Achievement of DLQI 0/1 for subjects with DLQI > 1 at Baseline at Week 12. 13. Achievement of DLQI 0/1 for subjects with DLQI > 1 at Baseline at Week 24. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Blinded- better defines the study design, as there is a double-blind and single-blind period |
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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 | 4 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 107 |
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 |
Israel |
Japan |
Korea, Republic of |
New Zealand |
Taiwan |
Belgium |
Bulgaria |
Czechia |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Portugal |
Slovakia |
Spain |
United Kingdom |
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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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The end-of-study is defined as the date of end of study participation by the last subject in the last country where the study was conducted. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |