A Phase 3b/4 Randomized, Blinded, Treat-to-Target and Dose-Flexibility Study of Upadacitinib in Adult Subjects With Moderate to Severe Atopic Dermatitis
Overview
- Phase
- Phase 4
- Intervention
- Upadacitinib
- Conditions
- Atopic Dermatitis
- Sponsor
- AbbVie
- Enrollment
- 461
- Locations
- 106
- Primary Endpoint
- Percentage of Participants Achieving ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 24
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
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 evaluates the dosing flexibility of upadacitinib in adult participants with moderate to severe AD. Adverse events and change in the disease activity will be assessed.
Upadacitinib is an approved drug for the treatment of moderate to severe/active immune-mediated inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis (UC), Crohn's Disease (CD), and AD. The study is comprised of a 35-day Screening Period, a 12-week double-blind period and a 12-week single-blind period. During the double-blind period, participants are placed in 1 of 2 groups, called treatment arms and will be randomized in a 1:1 ratio to receive upadacitinib. At 12 weeks during the single blind period, participants will be blinded to the upadacitinib dose based on their EASI response and reassigned to in 1 of 4 arms. After the last study visit, there is a 30-day follow-up visit. Approximately 454 adult participants ages 18 to 64 with moderate to severe AD who are candidates for systemic therapy will be enrolled at up to 160 sites worldwide.
The study is comprised of a 12-week double-blind period, followed by a 12-week single-blind period. Participants will receive upadacitinib oral tablets once daily for up to 24 weeks.
There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). 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.
Investigators
Eligibility Criteria
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, vIGA-AD score \>= 3 and \>= 10% Body Surface Area (BSA) of AD involvement at the Baseline Visit.
- •Baseline weekly average of daily Worst Pruritus NRS \>=
- •Candidate for systemic treatment defined as prior use of systemic treatment for AD, OR previous inadequate response to TCS, TCI or PDE-4 inhibitors, OR for whom topical treatments are otherwise medically inadvisable.
Exclusion Criteria
- •Participants with current or past history of infection including:
- •Two or more episodes of herpes zoster, or one or more episodes of disseminated herpes zoster;
- •One or more episodes of disseminated herpes simplex (including eczema herpeticum);
- •Human immunodeficiency virus (HIV) infection defined as confirmed positive anti-HIV antibody (HIV Ab) test;
- •Active tuberculosis (TB) or meet TB exclusionary parameters (protocol specified requirements for TB testing);
- •Japan only: Positive result of beta-D-glucan (screening for Pneumocystis jirovecii infection) or two consecutive indeterminate results of beta-D-glucan during the Screening Period;
- •Active infection(s) requiring treatment with intravenous anti-infectives within 30 days, or oral/intramuscular anti-infectives within 14 days prior to the Baseline Visit;
- •Chronic recurring infection and/or active viral infection that, based on the investigator's clinical assessment, makes the participant an unsuitable candidate for the study;
- •COVID-19 infection: In participants who tested positive for COVID, at least 5 days must have passed since a COVID-19 positive test result for study entry of asymptomatic participants. Participants with mild/moderate COVID-19 infection can be enrolled if fever is resolved without use of antipyretics for 24 hours and other symptoms improved, or if 5 days have passed since the COVID-19 positive test result (whichever comes last). Participants may be rescreened if judged to be in good general health, as determined by the investigator based upon the medical history and physical examination.
- •Evidence of Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
Arms & Interventions
UPA 30 mg Double-Blind Treatment Period --> UPA 30 mg Single-Blind Treatment Period
At Week 12 in the Double-Blind Treatment Period, participants receiving 30 mg upadacitinib orally once daily (QD) achieving a \< 90% reduction in the Eczema Area and Severity Index (EASI) (\< EASI 90) were allocated to receive 30 mg upadacitinib orally once daily (QD) for 12 weeks during the Single-Blind Treatment Period.
Intervention: Upadacitinib
UPA 15 mg Double-Blind Treatment Period
Participants received 15 mg upadacitinib orally once daily (QD) for 12 weeks during the Double-Blind Treatment Period.
Intervention: Upadacitinib
UPA 30 mg Double-Blind Treatment Period
Participants received 30 mg upadacitinib orally once daily (QD) for 12 weeks during the Double-Blind Treatment Period.
Intervention: Upadacitinib
UPA 15 mg Double-Blind Treatment Period --> UPA 15 mg Single-Blind Treatment Period
At Week 12 in the Double-Blind Treatment Period, participants receiving 15 mg upadacitinib orally once daily (QD) achieving a ≥ 90% reduction in the Eczema Area and Severity Index (EASI) (≥ EASI 90) were allocated to receive 15 mg upadacitinib orally once daily (QD) for 12 weeks during the Single-Blind Treatment Period.
Intervention: Upadacitinib
UPA 15 mg Double-Blind Treatment Period --> UPA 30 mg Single-Blind Treatment Period
At Week 12 in the Double-Blind Treatment Period, participants receiving 15 mg upadacitinib orally once daily (QD) achieving a \< 90% reduction in the Eczema Area and Severity Index (EASI) (\< EASI 90) were allocated to receive 30 mg upadacitinib orally once daily (QD) for 12 weeks during the Single-Blind Treatment Period.
Intervention: Upadacitinib
UPA 30 mg Double-Blind Treatment Period --> UPA 15 mg Single-Blind Treatment Period
At Week 12 in the Double-Blind Treatment Period, participants receiving 30 mg upadacitinib orally once daily (QD) achieving a ≥ 90% reduction in the Eczema Area and Severity Index (EASI) (≥ EASI 90) were allocated to receive 15 mg upadacitinib orally once daily (QD) for 12 weeks during the Single-Blind Treatment Period.
Intervention: Upadacitinib
Outcomes
Primary Outcomes
Percentage of Participants Achieving ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 24
Time Frame: Baseline and Week 24
The EASI is a composite index with scores ranging from 0 to 72. Four atopic dermatitis (AD) disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) are assessed for severity on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement is assessed as a percentage by body area of head, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks), and converted to a score of 0 to 6. In each body region, the area is expressed as 0, 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%).
Secondary Outcomes
- Percentage of Participants Achieving ≥ 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 24(Baseline and Week 24)
- Percentage of Participants Achieving a 100% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 100) at Week 24(Baseline and Week 24)
- Percentage of Participants Achieving ≥ 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving a 100% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 100) at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) and Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 12 Among Those With WP-NRS > 1 at Baseline(Baseline and Week 12)
- Percentage of Participants Achieving a ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) and Worst Pruritus Numerical Rating Scale of 0 or 1 (WP-NRS 0/1) at Week 24 Among Those With WP-NRS > 1 at Baseline(Baseline and Week 24)
- Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vlGA-AD) of 0 or 1 at Week 12(At Week 12)
- Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vlGA-AD) of 0 or 1 at Week 24(At Week 24)
- Percentage of Participants Achieving an Improvement (Reduction) in Worst Pruritus Numerical Rating Scale (WP-NRS) ≥4 at Week 12 Among Those With Baseline WP-NRS ≥4(Baseline and Week 12)
- Percentage of Participants Achieving an Improvement (Reduction) in Worst Pruritus Numerical Rating Scale (WP-NRS) ≥4 at Week 24 Among Those With Baseline WP-NRS ≥4(Baseline and Week 24)
- Percentage of Participants Achieving Worst Pruritus Numerical Rating Scale (WP-NRS) of 0 or 1 at Week 12 Among Those With Baseline WP-NRS >1(Baseline and Week 12)
- Percentage of Participants Achieving Worst Pruritus Numerical Rating Scale (WP-NRS) of 0 or 1 at Week 24 Among Those With Baseline WP-NRS >1(Baseline and Week 24)
- Percentage of Participants Achieving Improvement (Reduction) in Dermatology Life Quality Index (DLQI) ≥4 at Week 12 Among Those With Baseline DLQI ≥4(Baseline and Week 12)
- Percentage of Participants Achieving Improvement (Reduction) in Dermatology Life Quality Index (DLQI) ≥4 at Week 24 Among Those With Baseline DLQI ≥4(Baseline and Week 24)
- Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) of 0 or 1 At Week 12 Among Those With Baseline DLQI >1(Baseline and Week 12)
- Percentage of Participants Achieving Dermatology Life Quality Index (DLQI) of 0 or 1 At Week 24 Among Those With Baseline DLQI >1(Baseline and Week 24)