A Study to Assess Treat-to-Target and Dosing Flexibility of Oral Upadacitinib Tablets in Adult Participants With Moderate to Severe Atopic Dermatitis

Phase 4

Completed

Conditions: Atopic Dermatitis

Interventions: Drug: Upadacitinib

Registration Number: NCT05507580

Lead Sponsor: AbbVie

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 461

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 >= 4.
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).
Any of the following medical diseases or disorders:
- Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, and aorto-coronary bypass surgery;
- History of an organ transplant which requires continued immunosuppression;
- History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class;
- History of gastrointestinal perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for gastrointestinal perforation per investigator judgment;
- Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery; participants with a history of gastric banding/segmentation are not excluded;
- History of malignancy except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
UPA 15 mg Double-Blind Treatment Period	Upadacitinib	Participants received 15 mg upadacitinib orally once daily (QD) for 12 weeks during the Double-Blind Treatment Period.
UPA 30 mg Double-Blind Treatment Period	Upadacitinib	Participants received 30 mg upadacitinib orally once daily (QD) for 12 weeks during the Double-Blind Treatment Period.
UPA 15 mg Double-Blind Treatment Period --> UPA 15 mg Single-Blind Treatment Period	Upadacitinib	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.
UPA 15 mg Double-Blind Treatment Period --> UPA 30 mg Single-Blind Treatment Period	Upadacitinib	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.
UPA 30 mg Double-Blind Treatment Period --> UPA 15 mg Single-Blind Treatment Period	Upadacitinib	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.
UPA 30 mg Double-Blind Treatment Period --> UPA 30 mg Single-Blind Treatment Period	Upadacitinib	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 24	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 Outcome Measures

Name	Time	Method
Percentage of Participants Achieving ≥ 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 24	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%).
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	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%).
Percentage of Participants Achieving ≥ 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 12	Baseline and Week 12	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%).
Percentage of Participants Achieving ≥ 90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 90) at Week 12	Baseline and Week 12	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%).
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	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%).
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	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) 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%). The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
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	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) 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%). The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vlGA-AD) of 0 or 1 at Week 12	At Week 12	vIGA-AD is a validated assessment instrument used in clinical studies to rate the severity of AD globally. A 5-point scale is used to measure the severity of disease at the time of the investigator's evaluation of the participant ranging from 0 - Clear (no inflammatory signs of atopic dermatitis \[no erythema, no induration/papulation, no lichenification, no oozing/crusting\] Post-inflammatory hyperpigmentation and/or hypopigmentation may be present) to 4 - Severe (marked erythema \[deep or bright red\], marked induration/papulation, and/or marked lichenification).
Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vlGA-AD) of 0 or 1 at Week 24	At Week 24	vIGA-AD is a validated assessment instrument used in clinical studies to rate the severity of AD globally. A 5-point scale is used to measure the severity of disease at the time of the investigator's evaluation of the participant ranging from 0 - Clear (no inflammatory signs of atopic dermatitis \[no erythema, no induration/papulation, no lichenification, no oozing/crusting\] Post-inflammatory hyperpigmentation and/or hypopigmentation may be present) to 4 - Severe (marked erythema \[deep or bright red\], marked induration/papulation, and/or marked lichenification).
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	The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
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	The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
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	The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
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	The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants rated itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
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	DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of atopic dermatitis (AD) disease symptoms and treatment on health-related quality of life (HRQoL). It consists of 10 questions assessing impact of skin diseases on different aspects of participant's QoL over the prior week. Each item is scored on a 4-point scale: 0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much. Item scores (0 to 3) are added to provide a total score range of 0 to 30. Higher scores indicate greater impairment of HRQoL.
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	DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of atopic dermatitis (AD) disease symptoms and treatment on health-related quality of life (HRQoL). It consists of 10 questions assessing impact of skin diseases on different aspects of participant's QoL over the prior week. Each item is scored on a 4-point scale: 0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much. Item scores (0 to 3) are added to provide a total score range of 0 to 30. Higher scores indicate greater impairment of HRQoL.
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	DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of atopic dermatitis (AD) disease symptoms and treatment on health-related quality of life (HRQoL). It consists of 10 questions assessing impact of skin diseases on different aspects of participant's QoL over the prior week. Each item is scored on a 4-point scale: 0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much. Item scores (0 to 3) are added to provide a total score range of 0 to 30. Higher scores indicate greater impairment of HRQoL.
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	DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of atopic dermatitis (AD) disease symptoms and treatment on health-related quality of life (HRQoL). It consists of 10 questions assessing impact of skin diseases on different aspects of participant's QoL over the prior week. Each item is scored on a 4-point scale: 0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much. Item scores (0 to 3) are added to provide a total score range of 0 to 30. Higher scores indicate greater impairment of HRQoL.

Trial Locations

Locations (106): Momentum Clinical Research /ID# 254028
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Darlinghurst, New South Wales, Australia
Premier Specialist /ID# 246150
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Kogarah, New South Wales, Australia
Veracity Clinical Research /ID# 246154
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Woolloongabba, Queensland, Australia
North Eastern Health Specialists /ID# 246153
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Campbelltown, South Australia, Australia
Skin Health Institute Inc /ID# 246146
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Carlton, Victoria, Australia
Cliniques Universitaires UCL Saint-Luc /ID# 245842
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Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium
Grand Hôpital De Charleroi - Notre Dame /ID# 245837
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Charleroi, Hainaut, Belgium
AZ Sint-Lucas /ID# 253708
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Gent, Oost-Vlaanderen, Belgium
Dermatologie Maldegem /ID# 245840
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Maldegem, Oost-Vlaanderen, Belgium
CHU de Liege /ID# 245839
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Liege, Belgium
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Momentum Clinical Research /ID# 254028
🇦🇺Darlinghurst, New South Wales, Australia