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 (Level Up)

AbbVie

Status and phase: Completed; Phase 3

Conditions: Atopic Dermatitis

Treatments: Drug: Upadacitinib; Drug: Dupilumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05601882

M23-696

2022-002482-15 (EudraCT Number)

Details and patient eligibility

About

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. Participants are randomly assigned to 1 of 2 groups called treatment arms to receive upadacitinib Dose A or dupilumab in Period 1. There is a 30-day or 12-week follow-up visit for those on upadacitinib or dupilumab respectively, who will not enter Period 2. In Period 2, participants will receive upadacitinib Dose A or Dose B for 16 weeks, followed by a 30-day follow-up visit. 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.

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.

Enrollment: 920 patients

Sex: All

Ages: 12 to 64 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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920 participants in 4 patient groups

Dupilumab (Period 1)

Experimental group

Description:

Adult participants received a loading dose of 600 mg dupilumab by subcutaneous (SC) injection at the Baseline visit followed by 300 mg dupilumab SC every other week (EOW) until Week 16. Adolescents (12 to 17 years of age and weighing at least 40 kg) received treatment according to their body weight. Participants weighing 40 to \< 60 kg received a loading dose of 400 mg dupilumab SC at the Baseline visit followed by 200 mg SC EOW until Week 16. Those weighing 60 kg or more received a loading dose of 600 mg dupilumab SC at the Baseline visit followed by 300 mg dupilumab SC EOW until Week 16.

Treatment:

Drug: Dupilumab

Upadacitinib (Period 1)

Experimental group

Description:

Participants received 15 mg upadacitinib orally once a day (QD) up to Week 16. Starting at Week 4, participants had their dose increased to 30 mg QD if they had a \< 50% reduction from Baseline in Eczema Area and Severity Index (EASI 50) response or a \< 4-point improvement from Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS; weekly average). Starting at Week 8, participants had their dose increased to 30 mg QD if they had a \< EASI 75 response.

Treatment:

Drug: Upadacitinib

Dupilumab -> Upadacitinib (Period 2)

Experimental group

Description:

At Week 16, participants receiving dupilumab as per its label in Period 1 were reassigned based on their Eczema Area and Severity Index (EASI) response. Those with \< EASI 75 were offered the option to receive oral doses of upadacitinib 15 mg QD in Period 2 up to Week 32. Those with ≥ EASI 75 completed the end of study procedures. Starting at Week 20, participants with \< EASI 75 or a \< 4-point improvement from Baseline in Worst Pruritus Numerical Rating Scale (WP-NRS; weekly average) had their dose increased to 30 mg QD up to Week 32.

Treatment:

Drug: Upadacitinib

Upadacitinib -> Upadacitinib 30 mg (Period 2)

Experimental group

Description:

At Week 16, participants receiving upadacitinib in Period 1 were reassigned based on their Eczema Area and Severity Index (EASI) response. Those with \< EASI 75 were allocated or continued to receive upadacitinib 30 mg QD in Period 2. Those with ≥ EASI 75 completed the end of study procedures.

Treatment:

Drug: Upadacitinib