A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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This study will evaluate upadacitinib compared to dupilumab (Dupixent®) in adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Detailed Description
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The study is comprised of a 35-day screening period, a 24-week double-blinded treatment period, and a follow-up visit 12 weeks after the last dose. Participants who complete Week 24 have the option to enroll into an open-label study (Study M19-850; NCT04195698) of upadacitinib 30 mg once daily and receive treatment with upadacitinib for an additional 52 weeks. Participants who meet eligibility criteria will be randomized in a 1:1 ratio to receive either upadacitinib or dupilumab. Randomization will be stratified by Baseline disease severity (Validated Investigator Global Assessment scale for Atopic Dermatitis [vIGA-AD] score of moderate [3] versus severe [4]) and age (<40, ≥ 40 to < 65, ≥ 65 years).

Official Title
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A Phase 3b Multicenter, Randomized, Double-Blind, Double-Dummy, Active Controlled Study Comparing the Safety and Efficacy of Upadacitinib to Dupilumab in Adult Subjects With Moderate to Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Biological: Upadacitinib
* Biological: Dupilumab
* Drug: Placebo to dupilumab
* Drug: Placebo to upadacitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has active moderate to severe atopic dermatitis (AD) defined by Eczema Area and Severity Index (EASI) ≥ 16, Investigator's Global Assessment (IGA) ≥ 3, ≥ 10% body surface area (BSA) of AD involvement at the Screening and Baseline Visits, and Baseline weekly average of daily Worst Pruritus NRS ≥ 4. Participant is a candidate for systemic therapy or have recently required systemic therapy for AD. Exclusion Criteria: Participant has prior exposure to Janus Kinase (JAK) inhibitor. Participant has prior exposure to dupilumab. Participant is unable or unwilling to discontinue current AD treatments prior to the study. Participant has requirement of prohibited medications during the study. Participant has other active skin diseases or skin infections requiring systemic treatment or would interfere with appropriate assessment of AD lesions. Female participant who is pregnant, breastfeeding, or considering pregnancy during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upadacitinib 30 mg QD<br>Participants will receive 30 mg upadacitinib orally once a day (QD) up to Week 24 and placebo to dupilumab by subcutaneous injection every other week from Baseline to Week 22. | Biological: Upadacitinib<br>* Extended release tablet<br>* Other names: RINVOQ®;Drug: Placebo to dupilumab<br>* Placebo administered as a subcutaneous injection<br>|
| Experimental: Dupilumab 300 mg EOW<br>Participants will receive a loading dose of 600 mg dupilumab by subcutaneous (SC) injection on Day 1 followed by 300 mg dupilumab SC every other week (EOW) until Week 22 and placebo to upadacitinib orally QD up to Week 24. | Biological: Dupilumab<br>* Dupilumab is administered as a subcutaneous (SC) injection<br>* Other names: Dupixent®;Drug: Placebo to upadacitinib<br>* Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 16 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. | Baseline and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 16 | The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). The percent change from Baseline was calculated from a rolling weekly average; a negative change from Baseline indicates improvement. | Baseline (Week 0) to Week 16 | 
| Percentage of Participants Achieving a 100% Reduction From Baseline in EASI Score (EASI 100) at Week 16 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. | Baseline and Week 16 | 
| Percentage of Participants Achieving a 90% Reduction From Baseline in EASI Score (EASI 90) at Week 16 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. | Baseline and Week 16 | 
| Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 4 | The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). The percent change from Baseline was calculated from a rolling weekly average; a negative change from Baseline indicates improvement. | Baseline (Week 0) to Week 4 | 
| Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score at Week 2 | EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema). The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease. | Baseline and Week 2 | 
| Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 1 | The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). The percent change from Baseline was calculated from a rolling weekly average; a negative change from Baseline indicates improvement. | Baseline (Week 0) to Week 1 | 
| Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 16 | The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). | Baseline and Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABT-494, Upadacitinib, Dupilumab, Atopic Dermatitis