A Study to Evaluate ABT-494 (Upadacitinib) in Adults With Moderate to Severe Atopic Dermatitis
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| ClinicalTrials.gov Identifier: NCT02925117 |
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Recruitment Status :
Completed
First Posted : October 5, 2016
Results First Posted : July 16, 2020
Last Update Posted : July 16, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Atopic Dermatitis | Drug: Upadacitinib Drug: Placebo | Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 167 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | October 25, 2016 |
| Actual Primary Completion Date : | August 10, 2017 |
| Actual Study Completion Date : | January 31, 2019 |
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: 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.
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Drug: Upadacitinib
Tablet for oral use
Other Names:
Drug: Placebo Tablet |
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Experimental: 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.
|
Drug: Upadacitinib
Tablet for oral use
Other Names:
Drug: Placebo Tablet |
|
Experimental: 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.
|
Drug: Upadacitinib
Tablet for oral use
Other Names:
Drug: Placebo Tablet |
|
Experimental: 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.
|
Drug: Upadacitinib
Tablet for oral use
Other Names:
Drug: Placebo Tablet |
- 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.
- Percentage of Participants Who Achieved a 75% Reduction in EASI Score (EASI 75) at Week 16 [ Time Frame: Baseline and Week 16 ]
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease.
An EASI 75 response is defined as participants with at least a 75% reduction (improvement) in EASI score relative to the Baseline value.
Participants with missing values at Week 16 were counted as non-responders in this analysis (non-responder imputation).
- Percentage of Participants Achieving an Investigator Global Assessment (IGA) of "0" or "1" at Week 16 [ Time Frame: Week 16 ]
The Investigator's Global Assessment for Atopic Dermatitis (IGA) was scored on the following scale:
- 0: Clear (No inflammatory signs of atopic dermatitis)
- 1: Almost Clear (Just perceptible erythema and just perceptible papulation/infiltration)
- 2: Mild (Mild erythema and mild papulation/infiltration)
- 3: Moderate (Moderate erythema and moderate papulation/infiltration)
- 4: Severe (Severe erythema and severe papulation/infiltration with or without oozing/crusting)
The percentage of participants with a score of 0 or 1 at Week 16 is reported.
- Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) [ Time Frame: Baseline and Weeks 2, 8, and 16 ]Participants were asked to rate pruritus (itch) in the past 24 hours on a daily basis using a scale from 0 to 10, with 0 being no itch and 10 being the worst imaginable itch. The percent change from Baseline at each week was calculated from a rolling weekly average.
- Percent Change From Baseline in EASI Score at Week 8 [ Time Frame: Baseline and Week 8 ]
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.
- Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Weeks 8 and 16 [ Time Frame: Baseline and Weeks 8 and 16 ]SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst). A negative change from Baseline indicates improvement.
- Percentage of Participants Who Achieved an EASI 75 Response at Week 8 [ Time Frame: Baseline and Week 8 ]
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease.
An EASI 75 response is defined as participants with at least a 75% reduction (improvement) in EASI score relative to the Baseline value.
Participants with missing values at Week 8 were counted as non-responders in this analysis (non-responder imputation).
- Percentage of Participants Who Achieved an EASI 50 Response at Weeks 8 and 16 [ Time Frame: Baseline and Weeks 8 and 16 ]
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease.
An EASI 50 response is defined as participants with at least a 50% reduction (improvement) in EASI score relative to the Baseline value.
Participants with missing values at each time point were counted as non-responders in this analysis (non-responder imputation).
- Percentage of Participants Who Achieved an EASI 90 Response at Weeks 8 and 16 [ Time Frame: Baseline and Weeks 8 and 16 ]
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease.
An EASI 90 response is defined as participants with at least a 90% reduction (improvement) in EASI score relative to the Baseline value.
Participants with missing values at each time point were counted as non-responders in this analysis (non-responder imputation).
- Percentage of Participants Who Achieved a SCORAD 50 Response at Weeks 8 and 16 [ Time Frame: Baseline and Weeks 8 and 16 ]
SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst).
A SCORAD 50 response is defined as participants with at least a 50% reduction (improvement) in SCORAD score relative to the Baseline value.
Participants with missing values were counted as non-responders in this analysis (non-responder imputation).
- Percentage of Participants Who Achieved a SCORAD 75 Response at Weeks 8 and 16 [ Time Frame: Baseline and Weeks 8 and 16 ]
SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst).
A SCORAD 75 response is defined as participants with at least a 75% reduction (improvement) in SCORAD score relative to the Baseline value.
Participants with missing values were counted as non-responders in this analysis (non-responder imputation).
- Percentage of Participants Who Achieved a SCORAD 90 Response at Weeks 8 and 16 [ Time Frame: Baseline and Weeks 8 and 16 ]
SCORAD is a clinical tool used to assess the extent and severity of eczema (SCORing Atopic Dermatitis). The extent is assessed using the rule of 9 to calculate the affected area (A) as a percentage of the whole body (0-100%). The intensity part of the SCORAD (B) consists of 6 items: erythema, oedema/papulation, excoriations, lichenification, oozing/crusts and dryness, each graded on a scale from 0 (none) to 3 (severe), for a total score of 0 to 18. Subjective items (C) include daily pruritus and sleeplessness, each scored on a visual analogue scale (VAS) from 0 to 10 (total score 0-20). SCORAD is calculated as A/5 + 7B/2 + C, and ranges from 0 to 103 (worst).
A SCORAD 90 response is defined as participants with at least a 90% reduction (improvement) in SCORAD score relative to the Baseline value.
Participants with missing values were counted as non-responders in this analysis (non-responder imputation).
- Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 [ Time Frame: Re-randomization (Week 16) and Weeks 20, 24, 32, 40, 52, 64, 76, and 88 ]
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.
- Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 [ Time Frame: From re-randomization at Week 16 until Week 88 ]
Time to loss of EASI 50 response in Period 2 relative to Baseline among those who were re-randomized as EASI 75 responders at Week 16.
Time to loss of EASI 50 response was measured from Week 16 to the date of the first assessment in Period 2 where a participant's EASI score was higher than 50% of their Baseline score.
Participants with no loss of response were censored at their last treatment visit or the start of rescue treatment, whichever occurred first.
- 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 [ Time Frame: Weeks 20, 24, 32, 40, 52, 64, 76, and 88 ]
EASI is a tool to measure the extent and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the percentage of skin affected, and the severity of eczema (scored as none [0], mild [1], moderate [2], or severe [3]) for redness, thickness, scratching, and lichenification are assessed. The EASI score is the sum of the scores for each region and ranges from 0 to 72, where higher scores represent worse disease.
An EASI 75 response is defined as at least a 75% reduction (improvement) in EASI score relative to the Baseline value, and was analyzed in participants who were re-randomized at Week 16 and were EASI 75 non-responders at Week 16.
- Percentage of Participants Who Achieved a Dermatology Life Quality Index (DLQI) of "0" or "1" at Weeks 8 and 16 [ Time Frame: Weeks 8 and 16 ]
The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week in the following 6 aspects: symptoms and feelings, daily activities, leisure, work or school activities, personal relationships and treatment related feelings. Participants answer the 10 questions on a scale from 0 (not at all) to 3 (very much). The DLQI is calculated by summing the scores of the 10 questions, resulting in a maximum of 30 and a minimum of 0 with higher scores indicating more impaired quality of life. A score of 0 or 1 means that the disease has no effect at all.
Dermatology Life Quality Index outcomes were defined but are not reported because of an error in the programming of the electronic device used to administer the questionnaire that precluded determination of these outcomes.
- Change From Baseline in DLQI at Weeks 8 and 16 [ Time Frame: Baseline and Weeks 8 and 16 ]
The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week in the following 6 aspects: symptoms and feelings, daily activities, leisure, work or school activities, personal relationships and treatment related feelings. Participants answer the 10 questions on a scale from 0 (not at all) to 3 (very much). The DLQI is calculated by summing the scores of the 10 questions, resulting in a maximum of 30 and a minimum of 0 with higher scores indicating more impaired quality of life. A negative change from Baseline indicates improvement.
Dermatology Life Quality Index outcomes were defined but are not reported because of an error in the programming of the electronic device used to administer the questionnaire that precluded determination of these outcomes.
- Change From Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at Week 16 [ Time Frame: Baseline and Week 16 ]
Body surface area (BSA) affected by atopic dermatitis was assessed by the physician and is expressed as a percentage of the total BSA. For purposes of the estimation, the total surface of the participant's palm plus five digits was assumed to be approximately equivalent to 1% BSA.
Last observation carried forward imputation was used.
- Percentage of Participants With Reduction of ≥ 4 Points From Baseline in Pruritus NRS at Week 16 [ Time Frame: Baseline and Week 16 ]Participants were asked to rate pruritus (itch) in the past 24 hours on a daily basis using a scale from 0 to 10, with 0 being no itch and 10 being the worst imaginable itch. The percentage of participants with reduction of ≥ 4 points from Baseline in pruritus NRS was assessed in participants with a baseline pruritus NRS of ≥ 4. Participants with missing values at Week 16 were counted as non-responders in this analysis (non-responder imputation).
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02925117
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| Study Director: | AbbVie Inc. | AbbVie |
Documents provided by AbbVie:
| Responsible Party: | AbbVie |
| ClinicalTrials.gov Identifier: | NCT02925117 |
| Other Study ID Numbers: |
M16-048 2016-002451-21 ( EudraCT Number ) |
| First Posted: | October 5, 2016 Key Record Dates |
| Results First Posted: | July 16, 2020 |
| Last Update Posted: | July 16, 2020 |
| Last Verified: | July 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. |
| Access Criteria: | Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link. |
| URL: | https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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ABT-494 Atopic Dermatitis |
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Dermatitis, Atopic Dermatitis Eczema Skin Diseases Skin Diseases, Genetic Genetic Diseases, Inborn Skin Diseases, Eczematous Hypersensitivity, Immediate |
Hypersensitivity Immune System Diseases Upadacitinib Janus Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antirheumatic Agents |