Clinical trial NCT02925117: A Study to Evaluate ABT-494 (Upadacitinib) in Adults With Moderate to Severe Atopic Dermatitis
Official title: A Phase 2b Multicenter, Randomized, Placebo-Controlled, Double-Blind Dose-Ranging Study to Evaluate ABT-494 (Upadacitinib) in Adult Subjects With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Keywords: ABT-494
Atopic Dermatitis
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-10-05
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Percentage of Participants Who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants Achieving an Investigator Global Assessment (IGA) of "0" or "1" at Week 16
timeFrame: Week 16
measure: Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS)
timeFrame: Baseline and Weeks 2, 8, and 16
measure: Percent Change From Baseline in EASI Score at Week 8
timeFrame: Baseline and Week 8
measure: Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16
timeFrame: Baseline and Weeks 8 and 16
measure: Percentage of Participants Who Achieved an EASI 75 Response at Week 8
timeFrame: Baseline and Week 8
measure: Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16
timeFrame: Baseline and Weeks 8 and 16
measure: Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16
timeFrame: Baseline and Weeks 8 and 16
measure: Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16
timeFrame: Baseline and Weeks 8 and 16
measure: Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16
timeFrame: Baseline and Weeks 8 and 16
measure: Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16
timeFrame: Baseline and Weeks 8 and 16
measure: Percent Change From Re-randomization (Week 16) in EASI Score in Period 2
timeFrame: Re-randomization (Week 16) and Weeks 20, 24, 32, 40, 52, 64, 76, and 88
measure: Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16
timeFrame: From re-randomization at Week 16 until Week 88
measure: Percentage of Participants With an EASI 75 Response in Period 2 in Participants Who Were Re-randomized as EASI 75 Non-responders at Week 16
timeFrame: Weeks 20, 24, 32, 40, 52, 64, 76, and 88
measure: Percentage of Participants Who Achieved a Dermatology Life Quality Index (DLQI) of "0" or "1" at Weeks 8 and 16
timeFrame: Weeks 8 and 16
measure: Change From Baseline in DLQI at Weeks 8 and 16
timeFrame: Baseline and Weeks 8 and 16
measure: Change From Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With Reduction of ≥ 4 Points From Baseline in Pruritus NRS at Week 16
timeFrame: Baseline and Week 16
Other outcomes:
Locations:
city: Tampa
country: United States
facility: ForCare Clinical Research /ID# 157974
state: Florida
city: Sandy Springs
country: United States
facility: Advanced Medical Research /ID# 154516
state: Georgia
city: Rockville
country: United States
facility: DermAssociates /ID# 153584
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center /ID# 153586
state: Massachusetts
city: East Windsor
country: United States
facility: Psoriasis Treatment Ctr NJ /ID# 153578
state: New Jersey
city: New York
country: United States
facility: Icahn School of Med Mt. Sinai /ID# 153582
state: New York
city: Rochester
country: United States
facility: Univ Rochester Med Ctr /ID# 154477
state: New York
city: Arlington
country: United States
facility: Arlington Research Center, Inc /ID# 154522
state: Texas
city: Dallas
country: United States
facility: Modern Research Associates, PL /ID# 154487
state: Texas
city: Houston
country: United States
facility: Center for Clinical Studies /ID# 153589
state: Texas
city: Phillip
country: Australia
facility: Woden Dermatology /ID# 157907
state: Australian Capital Territory
city: Kogarah
country: Australia
facility: St George Hospital /ID# 157908
state: New South Wales
city: Woolloongabba
country: Australia
facility: Specialist Connect Pty Ltd /ID# 157909
state: Queensland
city: Carlton
country: Australia
facility: Skin Health Institute Inc /ID# 157906
state: Victoria
city: Calgary
country: Canada
facility: Institute for Skin Advancement /ID# 153246
state: Alberta
city: Surrey
country: Canada
facility: Dr. Chih-ho Hong Medical Inc. /ID# 153241
state: British Columbia
city: Surrey
country: Canada
facility: Enverus Medical Research /ID# 153239
state: British Columbia
city: Ajax
country: Canada
facility: CCA Medical Research /ID# 155817
state: Ontario
city: Markham
country: Canada
facility: Lynderm Research Inc. /ID# 153242
state: Ontario
city: Ottawa
country: Canada
facility: Dermatology Ottawa Research Centre /ID# 153248
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research /ID# 153244
state: Ontario
city: Turku
country: Finland
facility: Mehiläinen Neo /ID# 154960
state: Varsinais-Suomi
city: Mikkeli
country: Finland
facility: Mikkeli Central Hospital /ID# 154959
city: Hamburg
country: Germany
facility: TFS Trial Form Support GmbH /ID# 155442
city: Fukuoka-shi
country: Japan
facility: Fukuoka University Hospital /ID# 152714
state: Fukuoka
city: Obihiro-shi
country: Japan
facility: Takagi Dermatological Clinic /ID# 152706
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Medical Cooperation Kojinkai Sapporo Skin Clinic /ID# 153781
state: Hokkaido
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital /ID# 153287
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum /ID# 153688
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum /ID# 153596
state: Noord-Holland
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen /ID# 153595
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht /ID# 153687
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau /ID# 153519
city: Barcelona
country: Spain
facility: Hospital Univ Germans Trias I /ID# 155598
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.