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 for the treatment of adolescent and adult subjects with moderate to severe Atopic Dermatitis who are candidates for systemic therapy. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy and safety of 15 mg and 30mg upadacitinib for the treatment of adolescent and adult subjects with moderate to severe Atopic Dermatitis through up to 260 weeks in subjects who have completed week 16. |
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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
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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 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 EASI 75 at Week 2; • 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; • Proportion of subjects achieving an improvement (reduction) in Patient Oriented Eczema Measure (POEM) ≥ 4 from Baseline at Week 16 for subjects with POEM ≥ 4 at Baseline • Proportion of subjects age ≥ 16 years old at screening achieving an improvement (reduction) in Dermatology Life Quality Index (DLQI) ≥ 4 from Baseline at Week 16 for subjects with DLQI ≥ 4 at Baseline; • Proportion of subjects achieving an improvement (reduction) in Worst Pruritus NRS ≥ 4 from Baseline at Day 2 for subjects with Worst Pruritus NRS ≥ 4 at Baseline (upadacitinib 30 mg vs. placebo); • Proportion of subjects achieving an improvement (reduction) in Worst Pruritus NRS ≥ 4 from Baseline at Day 3 for subjects with Worst Pruritus NRS ≥ 4 at Baseline (upadacitinib 15 mg vs. placebo); • Proportion of subjects experiencing a flare, characterized as a clinically meaningful worsening in EASI, defined as an increase of EASI by ≥ 6.6 from Baseline for subjects with EASI ≤ 65.4 at Baseline, during double-blind treatment period (DB Period); • Percent change in Scoring Atopic Dermatitis (SCORAD) from Baseline at Week 16; • Proportion of subjects achieving a Hospital Anxiety and Depression Scale-anxiety (HADS-A) < 8 and Hospital Anxiety and Depression Scale-depression (HADS-D) < 8 at Week 16 among subjects with HADS-A ≥ 8 or HADS-D ≥ 8 at Baseline; • Proportion of subjects achieving an improvement (reduction) in Atopic Dermatitis Impact Scale (ADerm-IS) sleep domain score ≥ 12 (minimal clinically important difference [MCID]) from Baseline at Week 16 for subjects with ADerm-IS sleep domain score ≥12 at Baseline; • Proportion of subjects achieving an improvement (reduction) in Atopic Dermatitis Symptom Scale (ADerm-SS) skin pain score ≥ 4 (MCID) from Baseline at Week 16 for subjects with ADerm-SS skin pain score ≥ 4 at Baseline; • Proportion of subjects achieving an improvement (reduction) in ADerm-SS 7-item total symptom score (TSS-7) ≥ 28 (MCID) from Baseline at Week 16 for subjects with ADerm-SS TSS-7 ≥ 28 at Baseline; ADerm-SS TSS-7 is defined as the algebraic sum of the responses to items 1 – 7 of the ADerm-SS; • Proportion of subjects achieving an improvement (reduction) in ADerm-IS emotional state domain score ≥ 11 (MCID) from Baseline at Week 16 for subjects with ADerm-IS emotional state domain score ≥ 11 at Baseline; • Proportion of subjects achieving an improvement (reduction) in ADerm-IS daily activities domain score ≥ 14 (MCID) from Baseline at Week 16 for subjects with ADerm-IS daily activities domain score ≥ 14 at Baseline; • Proportion of subjects achieving EASI 100 at Week 16; • Proportion of subjects age ≥ 16 years old at screening achieving DLQI score of 0 or 1 at Week 16 for subjects with DLQI > 1 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 2 Week 1 Week 16 Week 16 Day 2 Day 3 DB Period Week 16 Week 16 Week 16 Week 16 Week 16 Week 16 Week 16 Week 16 Week 16 |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 |
Korea, Republic of |
New Zealand |
Singapore |
Taiwan |
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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The end-of-study is defined as the date of the last subject's last visit 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 | 5 |
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 | 5 |
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 |