A Study to Evaluate ABT-494 (Upadacitinib) in Adults With Moderate to Severe Atopic Dermatitis

NCT ID: NCT02925117

Last Updated: 2020-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 167 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-25
• Study Completion Date: 2019-01-31

Brief Summary

The objective of this study was to evaluate the safety and efficacy of multiple doses of upadacitinib monotherapy versus placebo in the treatment of adults with moderate to severe atopic dermatitis (AD).

Detailed Description

The study was to include a 16-week double-blind treatment period (Period 1) and a 72-week double-blind treatment period (Period 2) for a total of 88 weeks of treatment. Participants who met eligibility criteria were to be randomized in a 1:1:1:1 ratio to one of the four treatment groups. Participants who completed Period 1 were re-randomized at Week 16 into a 72-week double-blind, placebo-controlled treatment period (Period 2) in a 1:1 ratio:

• Group 1: Upadacitinib 7.5 mg once daily (QD) (Day 1 to Week 16) → upadacitinib 7.5 mg QD or placebo (Week 16 - and thereafter)
• Group 2: Upadacitinib 15 mg QD (Day 1 to Week 16) → upadacitinib 15 mg QD or placebo (Week 16 and thereafter)
• Group 3: Upadacitinib 30 mg QD (Day 1 to Week 16) → upadacitinib 30 mg QD or placebo (Week 16 - and thereafter)
• Group 4: Matching placebo (Day 1 to Week 16) → upadacitinib 30 mg QD or placebo (Week 16 and thereafter)

In Period 1, discontinuation from study drug was mandatory for any participant with an Eczema Area and Severity Index (EASI) score worsening of 25% or more compared with their Baseline EASI score at any 2 consecutive scheduled study visits from Week 4 to Week 12.

In Period 2, blinded rescue therapy with upadacitinib 30 mg QD was provided after the first instance of a < EASI 50 response starting at the Week 20 visit (4 weeks after re-randomization into Period 2) for the remainder of the study.

Conditions

Atopic Dermatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Participants randomized to receive placebo once daily (QD) for 16 weeks in Period 1. At Week 16 participants were re-randomized to receive 30 mg upadacitinib or placebo once a day for 72 weeks in Period 2.

Group Type: PLACEBO_COMPARATOR

Upadacitinib

Intervention Type: DRUG

Tablet for oral use

Placebo

Intervention Type: DRUG

Tablet

Upadacitinib 7.5 mg

Participants randomized to receive upadacitinib 7.5 mg QD for 16 weeks in Period 1. At Week 16 participants were re-randomized to receive 7.5 mg upadacitinib or placebo QD for 72 weeks in Period 2.

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablet for oral use

Placebo

Intervention Type: DRUG

Tablet

Upadacitinib 15 mg

Participants randomized to receive upadacitinib 15 mg QD for 16 weeks in Period 1. At Week 16 participants were re-randomized to receive 15 mg upadacitinib or placebo QD for 72 weeks in Period 2.

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablet for oral use

Placebo

Intervention Type: DRUG

Tablet

Upadacitinib 30 mg

Participants randomized to receive upadacitinib 30 mg QD for 16 weeks in Period 1. At Week 16 participants were re-randomized to receive 30 mg upadacitinib or placebo QD for 72 weeks in Period 2.

Group Type: EXPERIMENTAL

Upadacitinib

Intervention Type: DRUG

Tablet for oral use

Placebo

Intervention Type: DRUG

Tablet

Interventions

Upadacitinib

Tablet for oral use

Intervention Type: DRUG

Placebo

Tablet

Intervention Type: DRUG

Other Intervention Names

RINVOQ™; ABT-494

Eligibility Criteria

Inclusion Criteria

• Atopic dermatitis with a diagnosis confirmed by a dermatologist (according to the Hanifin and Rajka criteria) and onset of symptoms at least 1 year prior to Baseline.
• Moderate to severe atopic dermatitis defined by an Eczema Area and Severity Index (EASI) ≥ 16, body surface area (BSA) ≥ 10% and an Investigators Global Assessment (IGA) score ≥ 3 at the Baseline visit.
• Documented history (within 1 year prior to the screening visit) of inadequate response to treatment with topical corticosteroids (TCS), or topical calcineurin inhibitors (TCI), or for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks).
• Twice daily use of an additive-free, bland emollient for at least 7 days prior to Baseline.

Exclusion Criteria

• Prior exposure to any systemic or topical Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, ruxolitinib, and filgotinib).
• Treatment with topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin within 10 days prior to the Baseline visit.
• Prior exposure to dupilumab or exposure to systemic therapies for AD including corticosteroids, methotrexate, cyclosporine, azathioprine, phosphodiesterase type 4 (PDE4)-inhibitors and mycophenolate mofetil within 4 weeks prior to Baseline.
• Prior exposure to any investigational systemic treatment within 30 days or 5 half-lives (whichever is longer) of the Baseline visit or is currently enrolled in another clinical study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

ForCare Clinical Research /ID# 157974

Tampa, Florida, United States

Advanced Medical Research /ID# 154516

Sandy Springs, Georgia, United States

DermAssociates /ID# 153584

Rockville, Maryland, United States

Tufts Medical Center /ID# 153586

Boston, Massachusetts, United States

Psoriasis Treatment Ctr NJ /ID# 153578

East Windsor, New Jersey, United States

Icahn School of Med Mt. Sinai /ID# 153582

New York, New York, United States

Univ Rochester Med Ctr /ID# 154477

Rochester, New York, United States

Arlington Research Center, Inc /ID# 154522

Arlington, Texas, United States

Modern Research Associates, PL /ID# 154487

Dallas, Texas, United States

Center for Clinical Studies /ID# 153589

Houston, Texas, United States

Woden Dermatology /ID# 157907

Phillip, Australian Capital Territory, Australia

St George Hospital /ID# 157908

Kogarah, New South Wales, Australia

Specialist Connect Pty Ltd /ID# 157909

Woolloongabba, Queensland, Australia

Skin Health Institute Inc /ID# 157906

Carlton, Victoria, Australia

Institute for Skin Advancement /ID# 153246

Calgary, Alberta, Canada

Dr. Chih-ho Hong Medical Inc. /ID# 153241

Surrey, British Columbia, Canada

Enverus Medical Research /ID# 153239

Surrey, British Columbia, Canada

CCA Medical Research /ID# 155817

Ajax, Ontario, Canada

Lynderm Research Inc. /ID# 153242

Markham, Ontario, Canada

Dermatology Ottawa Research Centre /ID# 153248

Ottawa, Ontario, Canada

K. Papp Clinical Research /ID# 153244

Waterloo, Ontario, Canada

Mehiläinen Neo /ID# 154960

Turku, Southwest Finland, Finland

Mikkeli Central Hospital /ID# 154959

Mikkeli, , Finland

TFS Trial Form Support GmbH /ID# 155442

Hamburg, , Germany

Fukuoka University Hospital /ID# 152714

Fukuoka, Fukuoka, Japan

Takagi Dermatological Clinic /ID# 152706

Obihiro-shi, Hokkaido, Japan

Medical Cooperation Kojinkai Sapporo Skin Clinic /ID# 153781

Sapporo, Hokkaido, Japan

Nippon Medical School Hospital /ID# 153287

Tokyo, , Japan

Radboud Universitair Medisch Centrum /ID# 153688

Nijmegen, Gelderland, Netherlands

Academisch Medisch Centrum /ID# 153596

Amsterdam, North Holland, Netherlands

Universitair Medisch Centrum Groningen /ID# 153595

Groningen, , Netherlands

Universitair Medisch Centrum Utrecht /ID# 153687

Utrecht, , Netherlands

Hospital Santa Creu i Sant Pau /ID# 153519

Barcelona, , Spain

Hospital Univ Germans Trias I /ID# 155598

Barcelona, , Spain

Countries

United States; Australia; Canada; Finland; Germany; Japan; Netherlands; Spain

References

Guttman-Yassky E, Thaci D, Pangan AL, Hong HC, Papp KA, Reich K, Beck LA, Mohamed MF, Othman AA, Anderson JK, Gu Y, Teixeira HD, Silverberg JI. Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020 Mar;145(3):877-884. doi: 10.1016/j.jaci.2019.11.025. Epub 2019 Nov 29.

Reference Type: RESULT

PMID: 31786154 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-002451-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M16-048

Identifier Type: -

Identifier Source: org_study_id