A Study to Evaluate Adverse Events and Change in Disease Activity Comparing Oral Upadacitinib to Subcutaneous Dupilumab in Adolescent and Adult Participants With Moderate to Severe Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
Atopic dermatitis (AD) is a skin condition that may cause a rash and itching due to inflammation of the skin. Therapies spread over the skin may not be enough to control the AD in trial participants who require systemic anti-inflammatory treatment. This study compares upadacitinib to dupilumab in adolescent and adult participants with moderate to severe AD who have inadequate response to systemic therapies. Adverse events and change in the disease activity will be assessed. Upadacitinib and dupilumab are approved drugs for the treatment of moderate to severe atopic dermatitis (AD). The study is comprised of a 35-day Screening Period, a 16-week treatment period 1 and a 16-week treatment period 2. During period 1, participants are randomly assigned in 1 of 2 groups, called treatment arms to receive upadacitinib Dose A or dupilumab. In Period 2, participants will receive upadacitinib Dose A or Dose B. Approximately 880 adolescent and adult participants ages 12 to 64 with moderate to severe AD who are candidates for systemic therapy will be enrolled at up to 330 sites worldwide. Participants will receive upadacitinib oral tablets once daily or dupilumab as per its label for 32 weeks and followed for 30 days. There may be higher treatment burden for participants in this trial compared to their standard of care . Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Official Title
-----------------
A Phase 3b/4 Randomized, Open-label, Efficacy Assessor Blinded Study, Comparing the Safety and Assessor Blinded Efficacy of Upadacitinib to Dupilumab in Subjects With Moderate to Severe Atopic Dermatitis (Level-Up)

Conditions
-----------------
Atopic Dermatitis

Intervention / Treatment
-----------------
* Drug: Upadacitinib
* Drug: Dupilumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chronic atopic dermatitis (AD) with onset of symptoms at least 3 years prior to baseline and participant meets Hanifin and Rajka criteria. Eczema area and severity index (EASI) score ≥ 16;validated Investigator´s Global Assessment for AD (vIGA-AD) score ≥ 3 and ≥ 10% Body Surface Area Involvement of Atopic Dermatitis (BSA of AD) involvement at the Baseline Visit. Baseline weekly average of daily Worst Pruritus Numerical Rating Scale (WP-NRS) ≥ 4. Documented history of inadequate response to previous systemic treatment defined as documented history of previous inadequate response to at least one prior systemic treatment for AD OR for whom other systemic treatments are otherwise medically inadvisable. Exclusion Criteria: History of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months. History of an organ transplant which requires continued immunosuppression.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upadacitinib<br>Participants will receive upadacitinib dose A daily in period 1. Eligible participants will receive upadacitinib dose B daily in period 2. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: RINVOQ;|
| Experimental: Dupilumab followed by Upadacitinib<br>Participants will receive dupilumab as per its label in period 1. Eligible participants will receive upadacitinib dose A in period 2. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: RINVOQ;Drug: Dupilumab<br>* Subcutaneous Injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving both 90% Eczema Area and Severity Index (EASI 90) and Worst Pruritus Numerical Rating Scale of 0 or 1 (WPNRS 0/1) | The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72. The WP-NRS is an assessment tool that participants used to report the intensity of their pruritus during a daily recall period. On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst imaginable itch'. | At week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving at least 90% of Eczema Area and Severity Index (EASI 90) | The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of Atopic Dermatitis (AD). The EASI is a composite index with scores ranging from 0 to 72. | Up to week 16 | 
| Percentage of Participants Achieving a Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) among Participants with Baseline WP-NRS > 1 | The WP-NRS is an assessment tool that participants used to report the intensity of their pruritus during a daily recall period. On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst imaginable itch'. | Up to week 16 | 
| Percentage of Participants Achieving an improvement in Worst Pruritus Numerical Rating Scale (WP-NRS) ≥ 4 among those with Baseline WP-NRS ≥ 4 | The WP-NRS is an assessment tool that participants used to report the intensity of their pruritus during a daily recall period. On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst imaginable itch'. | At week 16 | 
| Percentage of Participants Achieving 75% of Eczema Area and Severity Index (EASI 75) | The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of Atopic Dermatitis (AD). The EASI is a composite index with scores ranging from 0 to 72. | At week 2 | 
| Percentage of Participants Achieving 100% of Eczema Area and Severity Index (EASI 100) | The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of Atopic Dermatitis (AD). The EASI is a composite index with scores ranging from 0 to 72. | At week 16 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Atopic Dermatitis, AD, Level-Up, Upadacitinib, Dupilumab, RINVOQ