A Study to Evaluate Upadacitinib in Combination With Topical Corticosteroids in Adolescent and Adult Participants With Moderate to Severe Atopic Dermatitis (AD Up)

AbbVie

Status and phase: Invitation-only; Phase 3

Conditions: Atopic Dermatitis

Treatments: Drug: Placebo; Drug: Upadacitinib; Drug: Topical corticosteroids (TCS)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03568318

M16-047

2017-005126-37 (EudraCT Number)

Details and patient eligibility

About

The objective of this study is to assess the efficacy and safety of upadacitinib combined with topical corticosteroids (TCS) for the treatment of adolescent and adult participants with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Full description

This study includes a 35-day screening period, a 16-week double-blind period, a blinded extension period up to Week 260, a blinded Long-term Extension (LTE) Period after Week 260 to Week 524, and a 30-day follow-up visit. Participants who meet eligibility criteria in the Main Study will be randomly assigned in a 1:1:1 ratio to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily, in combination with topical corticosteroids.

Upon completion of enrollment of 810 participants in the Main Study, a supplemental study will continue to enroll adolescent participants (Adolescent Sub-study) until a total of 180 adolescent participants are enrolled in the overall study (Main Study + Adolescent Sub-study).

Approximately 1000 participants from M16-045 or M18-891 and approximately 500 participants from M16-047 will have the opportunity to enroll into the blinded Long-Term Extension (LTE) period (Week 260 - Week 524) after reaching Week 260 in their respective studies.

Randomization for the Main Study will be stratified by Baseline disease severity (validated Investigator Global Assessment Scale for Atopic Dermatitis [vIGA-AD] score of moderate [3] versus severe [4]), by geographic region (US/Puerto Rico/Canada, Japan, China, and Other), and by age (adolescent [ages 12 to 17] versus adult [ages 18 to 75]). The separate randomization for the Adolescent Sub-study will be stratified by Baseline disease severity (moderate [vIGA-AD 3] versus severe [vIGA-AD 4]) and by geographic region (US/Puerto Rico/Canada and Other).

At Week 16 of both the Main Study and the Adolescent Sub-study, participants in the placebo group will be re-randomized in a 1:1 ratio to receive daily oral doses of upadacitinib 30 mg or upadacitinib 15 mg in the blinded extension period, and participants originally randomized to upadacitinib will continue upadacitinib in the extension period at the same dose. For the Main Study, the re-randomization will be stratified by Eczema Area and Severity Index (EASI) 50 responder status (Yes/No), by geographic region (US/Puerto Rico/Canada, Japan, China, and Other) and by age (adolescent [ages 12 to 17] versus adult [ages 18 to 75]). For the Adolescent Sub-study, the re-randomization will be stratified by EASI 50 responder (Yes/No) and by geographic region (US/Puerto Rico/Canada and Other).

Starting at Week 4, rescue treatment for AD may be provided at the discretion of the investigator if medically necessary The Primary Analysis for the Main Study will be conducted after all ongoing participants have completed Week 16. In addition, a Primary Analysis for the adolescent population (including the adolescent participants from the Main Study and the Adolescent Sub-study) will be conducted after all ongoing adolescent participants have completed Week 16.

Enrollment: 1,500 estimated patients

Sex: All

Ages: 12 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Body weight of ≥ 40 kg at Baseline Visit for participants ≥ 12 and < 18 years of age
• Chronic atopic dermatitis (AD) with onset of symptoms at least 3 years prior to Baseline Visit and subject meets Hanifin and Rajka criteria.
• Active moderate to severe atopic dermatitis defined by Eczema Area and Severity Index (EASI) ≥ 16, validated Investigator's Global Assessment (vIGA) ≥ 3, ≥ 10% of body surface area (BSA) with AD involvement, and weekly average of daily Worst Pruritus numerical rating scale (NRS) ≥ 4.
• Subject has applied a topical emollient (moisturizer) twice daily for at least 7 days before the Baseline Visit.
• Documented history of inadequate response to topical corticosteroids or topical calcineurin inhibitor OR documented systemic treatment for AD within 6 months prior to Baseline Visit

Exclusion criteria

• Prior exposure to any Janus kinase (JAK) inhibitor
• Unable or unwilling to discontinue current atopic dermatitis (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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,500 participants in 4 patient groups, including a placebo group

Placebo / Upadacitinib + Topical Corticosteroids

Placebo Comparator group

Description:

Participants will receive placebo orally once a day (QD) for 16 weeks in the double-blind treatment period. At Week 16 participants will be re-randomized to receive either upadacitinib 15 mg or upadacitinib 30 mg QD up to Week 260. Participants will also receive concomitant topical corticosteroids following a step-down regimen through Week 52.

Treatment:

Drug: Placebo

Drug: Upadacitinib

Drug: Topical corticosteroids (TCS)

Upadacitinib 15 mg QD + Topical Corticosteroids

Experimental group

Description:

Participants will receive upadacitinib 15 mg orally once a day for up to 260 weeks. Participants will also receive concomitant topical corticosteroids following a step-down regimen through Week 52.

Treatment:

Drug: Upadacitinib

Drug: Topical corticosteroids (TCS)

Upadacitinib 30 mg QD + Topical Corticosteroids

Experimental group

Description:

Participants will receive upadacitinib 30 mg orally once a day for up to 260 weeks. Participants will also receive concomitant topical corticosteroids following a step-down regimen through Week 52.

Treatment:

Drug: Upadacitinib

Drug: Topical corticosteroids (TCS)

Long-Term Extension

Experimental group

Description:

Participants who reach Week 260 in Studies M16-045, M18-891, and M16-047 will have the opportunity to roll over into the blinded LTE period of M16-047 to continue receiving the same daily dose of upadacitinib for up to Week 524.

Treatment:

Drug: Upadacitinib

Drug: Topical corticosteroids (TCS)