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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 167
- Locations
- 34
- Primary Endpoint
- Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: Placebo (Drug)
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.
Intervention: Upadacitinib (Drug)
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.
Intervention: Placebo (Drug)
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.
Intervention: Upadacitinib (Drug)
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.
Intervention: Placebo (Drug)
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.
Intervention: Upadacitinib (Drug)
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.
Intervention: Upadacitinib (Drug)
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 16
Time Frame: Baseline and 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; a negative change from baseline indicates improvement.
Secondary Outcomes
- Percentage of Participants Achieving an Investigator Global Assessment (IGA) of "0" or "1" at Week 16(Week 16)
- Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16(Baseline and Weeks 8 and 16)
- Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16(Baseline and Weeks 8 and 16)
- Percentage of Participants Who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16(Baseline and Week 16)
- Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS)(Baseline and Weeks 2, 8, and 16)
- Percent Change From Baseline in EASI Score at Week 8(Baseline and Week 8)
- Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16(Baseline and Weeks 8 and 16)
- Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16(From re-randomization at Week 16 until Week 88)
- 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(Weeks 20, 24, 32, 40, 52, 64, 76, and 88)
- Change From Baseline in DLQI at Weeks 8 and 16(Baseline and Weeks 8 and 16)
- Percentage of Participants Who Achieved an EASI 75 Response at Week 8(Baseline and Week 8)
- Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16(Baseline and Weeks 8 and 16)
- Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16(Baseline and Weeks 8 and 16)
- Percentage of Participants Who Achieved a Dermatology Life Quality Index (DLQI) of "0" or "1" at Weeks 8 and 16(Weeks 8 and 16)
- Change From Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16(Baseline and Week 16)
- Percentage of Participants With Reduction of ≥ 4 Points From Baseline in Pruritus NRS at Week 16(Baseline and Week 16)
- Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16(Baseline and Weeks 8 and 16)
- Percent Change From Re-randomization (Week 16) in EASI Score in Period 2(Re-randomization (Week 16) and Weeks 20, 24, 32, 40, 52, 64, 76, and 88)