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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02925117




Registration number
NCT02925117
Ethics application status
Date submitted
4/10/2016
Date registered
5/10/2016
Date last updated
16/07/2020

Titles & IDs
Public title
A Study to Evaluate ABT-494 (Upadacitinib) in Adults With Moderate to Severe Atopic Dermatitis
Scientific 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
Secondary ID [1] 0 0
2016-002451-21
Secondary ID [2] 0 0
M16-048
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic Dermatitis 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Upadacitinib
Treatment: Drugs - Placebo

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.

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.

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.

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.


Treatment: Drugs: Upadacitinib
Tablet for oral use

Treatment: Drugs: Placebo
Tablet

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at 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.
Timepoint [1] 0 0
Baseline and Week 16
Secondary outcome [1] 0 0
Percentage of Participants Who Achieved a 75% Reduction in EASI Score (EASI 75) at 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).
Timepoint [1] 0 0
Baseline and Week 16
Secondary outcome [2] 0 0
Percentage of Participants Achieving an Investigator Global Assessment (IGA) of "0" or "1" at 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.
Timepoint [2] 0 0
Week 16
Secondary outcome [3] 0 0
Percent Change From Baseline to Weeks 2, 8, and 16 in Pruritus Numerical Rating Scale (NRS) - 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.
Timepoint [3] 0 0
Baseline and Weeks 2, 8, and 16
Secondary outcome [4] 0 0
Percent Change From Baseline in EASI Score at 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.
Timepoint [4] 0 0
Baseline and Week 8
Secondary outcome [5] 0 0
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at 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.
Timepoint [5] 0 0
Baseline and Weeks 8 and 16
Secondary outcome [6] 0 0
Percentage of Participants Who Achieved an EASI 75 Response at 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).
Timepoint [6] 0 0
Baseline and Week 8
Secondary outcome [7] 0 0
Percentage of Participants Who Achieved an EASI 50 Response at 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).
Timepoint [7] 0 0
Baseline and Weeks 8 and 16
Secondary outcome [8] 0 0
Percentage of Participants Who Achieved an EASI 90 Response at 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).
Timepoint [8] 0 0
Baseline and Weeks 8 and 16
Secondary outcome [9] 0 0
Percentage of Participants Who Achieved a SCORAD 50 Response at 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).
Timepoint [9] 0 0
Baseline and Weeks 8 and 16
Secondary outcome [10] 0 0
Percentage of Participants Who Achieved a SCORAD 75 Response at 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).
Timepoint [10] 0 0
Baseline and Weeks 8 and 16
Secondary outcome [11] 0 0
Percentage of Participants Who Achieved a SCORAD 90 Response at 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).
Timepoint [11] 0 0
Baseline and Weeks 8 and 16
Secondary outcome [12] 0 0
Percent Change From Re-randomization (Week 16) in EASI Score in Period 2 - 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.
Timepoint [12] 0 0
Re-randomization (Week 16) and Weeks 20, 24, 32, 40, 52, 64, 76, and 88
Secondary outcome [13] 0 0
Time to Loss of EASI 50 Response Relative to Baseline Among Participants Re-randomized as EASI 75 Responders at Week 16 - 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.
Timepoint [13] 0 0
From re-randomization at Week 16 until Week 88
Secondary outcome [14] 0 0
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 - 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.
Timepoint [14] 0 0
Weeks 20, 24, 32, 40, 52, 64, 76, and 88
Secondary outcome [15] 0 0
Percentage of Participants Who Achieved a Dermatology Life Quality Index (DLQI) of "0" or "1" at 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.
Timepoint [15] 0 0
Weeks 8 and 16
Secondary outcome [16] 0 0
Change From Baseline in DLQI at 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.
Timepoint [16] 0 0
Baseline and Weeks 8 and 16
Secondary outcome [17] 0 0
Change From Baseline in Percentage of Body Surface Area (BSA) Affected by Atopic Dermatitis at 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.
Timepoint [17] 0 0
Baseline and Week 16
Secondary outcome [18] 0 0
Percentage of Participants With Reduction of = 4 Points From Baseline in Pruritus NRS at 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).
Timepoint [18] 0 0
Baseline and Week 16

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 0 0
Woden Dermatology /ID# 157907 - Phillip
Recruitment hospital [2] 0 0
St George Hospital /ID# 157908 - Kogarah
Recruitment hospital [3] 0 0
Specialist Connect Pty Ltd /ID# 157909 - Woolloongabba
Recruitment hospital [4] 0 0
Skin Health Institute Inc /ID# 157906 - Carlton
Recruitment postcode(s) [1] 0 0
2606 - Phillip
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3053 - Carlton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Canada
State/province [8] 0 0
Alberta
Country [9] 0 0
Canada
State/province [9] 0 0
British Columbia
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Finland
State/province [11] 0 0
Varsinais-Suomi
Country [12] 0 0
Finland
State/province [12] 0 0
Mikkeli
Country [13] 0 0
Germany
State/province [13] 0 0
Hamburg
Country [14] 0 0
Japan
State/province [14] 0 0
Fukuoka
Country [15] 0 0
Japan
State/province [15] 0 0
Hokkaido
Country [16] 0 0
Japan
State/province [16] 0 0
Tokyo
Country [17] 0 0
Netherlands
State/province [17] 0 0
Gelderland
Country [18] 0 0
Netherlands
State/province [18] 0 0
Noord-Holland
Country [19] 0 0
Netherlands
State/province [19] 0 0
Groningen
Country [20] 0 0
Netherlands
State/province [20] 0 0
Utrecht
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT02925117
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications