A Study to Evaluate Upadacitinib in Adolescents and Adults With Moderate to Severe Atopic Dermatitis (Measure Up 2)
Sponsor
AbbVie (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03607422
Collaborator
(none)
912
196
3
88.2
4.7
0.1
Study Details
Study Description
Brief Summary
The objective of this study is to assess the efficacy and safety of upadacitinib for the treatment of adolescent and adult participants with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This study includes a 35-day screening period, a 16-week double-blind period, a blinded extension period up to Week 260, and a 30-day follow-up visit.
Participants who meet eligibility criteria in the main study will be randomized in a 1:1:1 ratio to receive a daily oral dose of upadacitinib 30 mg or upadacitinib 15 mg or matching placebo. Upon completion of enrollment of a minimum of 810 participants in the main study, a supplemental study will continue to enroll adolescents (adolescent sub-study) until a total of 180 adolescent participants are enrolled overall (main study + adolescent sub-study).
Randomization in the main study will be stratified by baseline disease severity (validated Investigator Global Assessment scale for Atopic Dermatitis [vIGA-AD] score of moderate [3] versus severe [4]), by geographic region (United States [US]/Puerto Rico/Canada, and Other), and by age (adolescent [ages 12 to 17] versus adult [ages 18 to 75]). The separate randomization for the adolescent sub-study will be stratified by baseline disease severity (moderate [vIGA-AD = 3] vs. severe [vIGA-AD = 4]) and by geographic region (US/Puerto Rico/Canada and Other).
At Week 16 of the main study and the adolescent sub-study, participants in the placebo group will be re-randomized in a 1:1 ratio to receive daily oral doses of upadacitinib 30 mg or upadacitinib 15 mg in the blinded extension period. In the main study the re-randomization at Week 16 will be stratified by Week 16 50% improvement in Eczema Area and Severity Index [EASI 50] responder [Yes/No], geographic region [US/Puerto Rico/Canada, and other], and age group [adolescent/adult]. For the adolescent sub-study, the re-randomization will be stratified by EASI 50 responder (Yes/No) and by geographic region (US/Puerto Rico/Canada and Other). Participants originally randomized to upadacitinib will continue upadacitinib in the extension period at the same dose.
Starting at the Week 4 visit, rescue treatment for AD may be provided at the discretion of the investigator if medically necessary.
The Primary Analysis for the main study will be conducted after all ongoing participants have completed Week 16. In addition, a Primary Analysis for the adolescent population (including the adolescent participants from the main study and the adolescent sub-study) will be conducted after all ongoing adolescent participants have completed Week 16.
Study Design
Study Type:
Interventional
Actual Enrollment
:
912 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Upadacitinib in Adolescent and Adult Subjects With Moderate to Severe Atopic Dermatitis
Actual Study Start Date
:
Jul 27, 2018
Actual Primary Completion Date
:
Mar 11, 2021
Anticipated Study Completion Date
:
Dec 3, 2025
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo / Upadacitinib Participants will receive placebo orally once a day (QD) for 16 weeks in the double-blind treatment period. At Week 16 participants will be re-randomized to receive either upadacitinib 15 mg or upadacitinib 30 mg QD up to Week 260. |
Drug: Placebo for Upadacitinib
Tablets taken orally once a day
Drug: Upadacitinib
Tablets taken orally once a day
Other Names:
|
| Experimental: Upadacitinib 15 mg QD Participants will receive upadacitinib 15 mg orally once a day for up to 260 weeks. |
Drug: Upadacitinib
Tablets taken orally once a day
Other Names:
|
| Experimental: Upadacitinib 30 mg QD Participants will receive upadacitinib 30 mg orally once a day for up to 260 weeks. |
Drug: Upadacitinib
Tablets taken orally once a day
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Main Study: Percentage of Participants Achieving at Least a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) From Baseline at Week 16 [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.
- Main Study: Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16 [Baseline and Week 16]
The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale: 0 - Clear: No inflammatory signs of AD; 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification, no oozing or crusting; 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification, no oozing or crusting; 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present; 4 - Severe: Marked erythema, induration/papulation and/or lichenification; Oozing or crusting may be present.
Secondary Outcome Measures
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus Numerical Rating Scale (NRS) at Week 16 [Baseline (last available rolling average before the first dose of study drug) and Week 16]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
- Main Study: Percentage of Participants Achieving a 90% Reduction From Baseline in EASI Score (EASI 90) at Week 16 [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.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4 [Baseline (last available rolling average before the first dose of study drug) and Week 4]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
- Main Study: Percentage of Participants Achieving an EASI 75 Response at Week 2 [Baseline and Week 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. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1 [Baseline (last available rolling average before the first dose of study drug) and Week 1]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 2 [Baseline and Day 2]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11- point scale from 0 (no itch) to 10 (worst imaginable itch). The percentage of participants who had a 4-point or greater improvement from Baseline in Worst Pruritus NRS score at Day 2 was pre-specified as a ranked secondary endpoint for participants in the upadacitinib 30 mg group versus placebo group only.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 3 [Baseline and Day 3]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). The percentage of participants who had a 4-point or greater improvement in Worst Pruritus NRS score from Baseline at Day 3 was pre-specified as a ranked secondary endpoint for participants in the upadacitinib 15 mg group versus placebo group only.
- Main Study: Percentage of Participants Experiencing a Flare During the Double-blind Treatment Period [From first dose of study drug to Week 16]
A flare, characterized as a clinically meaningful worsening in EASI, is defined as an increase in EASI score of ≥ 6.6 points from Baseline during the double-blind treatment period and prior to use of any rescue medication. Flare was assessed in participants with an EASI score of 65.4 or less at Baseline.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 12 Points From Baseline in Atopic Dermatitis Impact Scale (ADerm-IS) Sleep Domain Score at Week 16 [Baseline (last available rolling average before the first dose of study drug) and Week 16]
The ADerm-IS is a 10-item patient reported outcome (PRO) questionnaire designed to assess a variety of impacts that participants experience from their AD. The ADerm-IS sleep domain consists of 3 questions designed to assess the impact of AD on sleep on a daily basis over a 24-hour recall period. The items include difficulty falling asleep, impact on sleep, and waking at night. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The ADerm-IS sleep domain score is the sum of the 3 item scores and ranges from 0 (no impact) to 30 (worst impact). The ADerm-IS sleep domain was analyzed based on weekly rolling averages of daily scores. The minimal clinically important difference for ADerm-IS sleep domain score is 12.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain Score at Week 16 [Baseline (last available rolling average before the first dose of study drug) and Week 16]
The ADerm-SS is an 11-item PRO questionnaire designed to assess signs and symptoms that patients may experience due to AD using a 24-hour recall period. For the skin pain item participants were asked on a daily basis to indicate how bad their worst skin pain due to AD was in the past 24 hours on an NRS from 0 (no pain) to 10 (worst imaginable pain). The ADerm-SS skin pain score was analyzed using weekly rolling averages of daily scores. The minimal clinically important difference for ADerm-SS skin pain score is 4.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 28 Points From Baseline in ADerm-SS 7-Item Total Symptom Score (TSS-7) at Week 16 [Baseline and Week 16]
The ADerm-SS is an 11-item questionnaire designed to assess signs and symptoms that participants may experience due to AD using a 24-hour recall period. The 7-item total symptom score includes 7 symptoms (items 1-7 of the ADerm-SS), each assessed on a NRS from 0 (no symptom) to 10 (worst imaginable). The 7 symptoms included in the score are itch while asleep, itch while awake, skin pain (each assessed daily), skin cracking, skin cracking pain, dry skin, and skin flaking (assessed weekly). The TSS-7 score ranges from 0 to 70, with higher scores indicating worsening symptoms. The minimal clinically important difference for ADerm-SS TSS-7 is 28.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 11 Points From Baseline in ADerm-IS Emotional State Domain Score at Week 16 [Baseline and Week 16]
The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD. ADerm-IS emotional state sums three items [Items 8-10] measuring self-consciousness, embarrassment, and sadness with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The emotional state domain score ranges from 0 to 30, where higher scores represent worst impact. The minimal clinically important difference for ADerm-IS emotional state domain score is 11.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 14 Points From Baseline in ADerm-IS Daily Activities Domain Score at Week 16 [Baseline and Week 16]
The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD. ADerm-IS Daily Activities sums four items measuring limitations of household, physical, and social activities, and difficulty concentrating with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The daily activities domain score ranges from 0 to 40, where higher scores represent worst impact. The minimal clinically important difference for the ADerm-IS daily activities domain score is 14.
- Main Study: Percentage of Participants Achieving a 100% Reduction From Baseline in EASI Score (EASI 100) at Week 16 [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.
- Main Study: Percent Change From Baseline in Worst Pruritus NRS at Week 16 [Baseline (last available rolling average before the first dose of study drug) and Week 16]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores. A negative change from Baseline indicates improvement.
- Main Study: Percent Change From Baseline in EASI Score at Week 16 [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.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Patient Oriented Eczema Measure (POEM) Total Score at Week 16 [Baseline and Week 16]
The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults. Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema). A change in POEM score of 3.4 points is considered the minimal clinically important difference.
- Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 [Baseline and Week 16]
The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. 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 are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. the DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit.
- Main Study: Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 [Baseline and Week 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.
- Main Study: Percentage of Participants Achieving a Hospital Anxiety and Depression Scale-Anxiety (HADS-A) Score and Hospital Anxiety and Depression Scale-Depression (HADS-D) Score of < 8 at Week 16 [Week 16]
The HADS is a 14-item questionnaire, with seven items related to anxiety (HADS-A) and seven items related to depression (HADS-D). Each item is scored from 0 to 3; scores for each subscale range from 0 to 21, with higher scores indicating more distress. For each domain, scores 7 or lower are considered normal, 8 to 10 are borderline, and 11 or higher indicate clinical anxiety or depression.
- Main Study: Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 16 [Week 16]
The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. 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 are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. A score of 0 or 1 means that the disease has no effect at all. The DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit.
- Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 16 [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. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
- Adolescents: Percentage of Participants Achieving a vIGA-AD of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16 [Baseline and Week 16]
The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale: 0 - Clear: No signs of AD; 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification, no oozing or crusting;; 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification, no oozing or crusting; 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, possible oozing or crusting; 4 - Severe: Marked erythema, induration/papulation and/or lichenification; possible oozing or crusting.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 16 [Baseline (last available rolling average before the first dose of study drug) and Week 16]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.
- Adolescents: Percentage of Participants Achieving an EASI 90 Response at Week 16 [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. An EASI 90 response is defined as at least a 90% reduction (improvement) from Baseline in EASI score.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4 [Baseline (last available rolling average before the first dose of study drug) and Week 4]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.
- Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 2 [Baseline and Week 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. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1 [Baseline (last available rolling average before the first dose of study drug) and Week 1]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 2 [Baseline and Day 2]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 3 [Baseline and Day 3]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).
- Adolescents: Percentage of Participants Experiencing a Flare During the Double-blind Treatment Period [From first dose of study drug to Week 16]
A flare, characterized as a clinically meaningful worsening in EASI, is defined as an increase in EASI score of ≥ 6.6 points from Baseline during the double-blind treatment period and prior to use of any rescue medication. Flares were assessed in participants with an EASI score of 65.4 or less at Baseline.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 12 Points From Baseline in ADerm-IS Sleep Domain Score at Week 16 [Baseline (last available rolling average before the first dose of study drug) and Week 16]
The ADerm-IS is a 10-item patient reported outcome questionnaire designed to assess a variety of impacts that participants experience from their AD. The ADerm-IS sleep domain consists of 3 questions designed to assess the impact of AD on sleep on a daily basis over a 24-hour recall period. The items include difficulty falling asleep, impact on sleep, and waking at night. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The ADerm-IS sleep domain score is the sum of the 3 item scores and ranges from 0 (no impact) to 30 (worst impact). The ADerm-IS sleep domain was analyzed based on weekly rolling averages of daily scores. The minimal clinically important difference for ADerm-IS sleep domain score is 12.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in ADerm-SS Skin Pain Score at Week 16 [Baseline (last available rolling average before the first dose of study drug) and Week 16]
The ADerm-SS is an 11-item PRO questionnaire designed to assess signs and symptoms that patients may experience due to AD using a 24-hour recall period. For the skin pain item participants were asked to indicate on a daily basis how bad their worst skin pain due to AD was in the past 24 hours on an NRS from 0 (no pain) to 10 (worst imaginable pain). The minimal clinically important difference for ADerm-SS skin pain score is 4. The ADerm-SS skin pain score was analyzed based on weekly rolling averages of daily scores.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 28 Points From Baseline in ADerm-SS TSS-7 at Week 16 [Baseline and Week 16]
The ADerm-SS is an 11-item questionnaire designed to assess signs and symptoms that participants may experience due to AD using a 24-hour recall period. The 7-item total symptom score includes 7 symptoms (items 1-7 of the ADerm-SS), each assessed on a NRS from 0 (no symptom) to 10 (worst imaginable). The 7 symptoms included in the score are itch while asleep, itch while awake, skin pain (each assessed daily), skin cracking, skin cracking pain, dry skin, and skin flaking (assessed weekly). The TSS-7 score ranges from 0 to 70, with higher scores indicating worsening symptoms. The minimal clinically important difference for ADerm-SS TSS-7 is 28.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 11 Points From Baseline in ADerm-IS Emotional State Domain Score at Week 16 [Baseline and Week 16]
The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD. ADerm-IS emotional state sums three items [Items 8-10] measuring self-consciousness, embarrassment, and sadness with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The emotional state domain score ranges from 0 to 30, where higher scores represent worst impact. The minimal clinically important difference for ADerm-IS emotional state domain score is 11.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 14 Points From Baseline in ADerm-IS Daily Activities Domain Score at Week 16 [Baseline and Week 16]
The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD. ADerm-IS daily activities sums four items measuring limitations of household, physical, and social activities, and difficulty concentrating with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The daily activities domain score ranges from 0 to 40, where higher scores represent worst impact. The minimal clinically important difference for the ADerm-IS daily activities domain score is 14.
- Adolescents: Percentage of Participants Achieving an EASI 100 Response at Week 16 [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. An EASI 100 response is defined as a 100% reduction (improvement) from Baseline in EASI score.
- Adolescents: Percent Change From Baseline in Worst Pruritus NRS at Week 16 [Baseline (last available rolling average before the first dose of study drug) and Week 16]
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores. A negative change from Baseline indicates improvement.
- Adolescents: Percent Change From Baseline in EASI Score at Week 16 [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.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in POEM Total Score at Week 16 [Baseline and Week 16]
The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults. Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema). A change in POEM score of 3.4 points is considered the minimal clinically important difference.
- Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in DLQI Score at Week 16 [Baseline and Week 16]
The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. 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 are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. the DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit.
- Adolescents: Percent Change From Baseline in SCORAD Score at Week 16 [Baseline and Week 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.
- Adolescents: Percentage of Participants Achieving HADS-A Score and HADS-D Score of < 8 at Week 16 [Week 16]
The HADS is a 14-item questionnaire, with seven items related to anxiety (HADS-A) and seven items related to depression (HADS-D). Each item is scored from 0 to 3; scores for each subscale range from 0 to 21, with higher scores indicating more distress. For each domain, scores 7 or lower are considered normal, 8 to 10 are borderline, and 11 or higher indicate clinical anxiety or depression.
- Adolescents: Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 16 [Week 16]
The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. 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 are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. A score of 0 or 1 means that the disease has no effect at all. the DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Body weight of ≥ 40 kg at Baseline Visit for participants ≥ 12 and < 18 years of age
-
Chronic atopic dermatitis (AD) with onset of symptoms at least 3 years prior to Baseline and subject meets Hanifin and Rajka criteria
-
Active moderate to severe AD defined by Eczema Area and Severity Index (EASI) ≥ 16, validated Investigator's Global Assessment (vIGA) ≥ 3, body surface area (BSA) affected by AD ≥ 10%, and weekly average of daily Worst Pruritus numerical rating scale (NRS) score ≥ 4.
-
Candidate for systemic therapy or have recently required systemic therapy for AD
-
Documented history (within 6 months prior to Baseline) of inadequate response to topical corticosteroid (TCS) or topical calcineurin inhibitor (TCI) or documented systemic treatment for AD or for whom topical treatments are otherwise medically inadvisable due to side effects or safety risks
Exclusion Criteria:
-
Prior exposure to any Janus kinase (JAK) inhibitor
-
Unable or unwilling to discontinue current AD treatments prior to the study
-
Requirement of prohibited medications during the study
-
Other active skin diseases or skin infections requiring systemic treatment or would interfere with appropriate assessment of atopic dermatitis lesions
-
Female subject who is pregnant, breastfeeding, or considering pregnancy during the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Total Skin and Beauty Derm Ctr /ID# 205129 | Birmingham | Alabama | United States | 35205 |
| 2 | Medical Dermatology Specialist /ID# 205516 | Phoenix | Arizona | United States | 85006-2722 |
| 3 | Arizona Research Center, Inc. /ID# 205795 | Phoenix | Arizona | United States | 85053-4061 |
| 4 | The Dermatology Clinic of Arkansas /ID# 218749 | Bryant | Arkansas | United States | 72022-7514 |
| 5 | Arkansas Research Trials /ID# 218469 | North Little Rock | Arkansas | United States | 72117 |
| 6 | Encino Research Center /ID# 207472 | Encino | California | United States | 91436 |
| 7 | University of California Irvine /ID# 205136 | Irvine | California | United States | 92697-1385 |
| 8 | Ark Clinical Research /ID# 218193 | Long Beach | California | United States | 90806-2325 |
| 9 | Keck School of Medicine of USC /ID# 206971 | Los Angeles | California | United States | 90033 |
| 10 | Wallace Medical Group /ID# 205701 | Los Angeles | California | United States | 90056 |
| 11 | Child Hosp of Orange County,CA /ID# 205735 | Orange | California | United States | 92868 |
| 12 | Palmtree Clinical Research Inc. /Id# 206184 | Palm Springs | California | United States | 92262 |
| 13 | Rady Children's Hospital San Diego /ID# 208244 | San Diego | California | United States | 92123 |
| 14 | Southern California Derma. Inc /ID# 205734 | Santa Ana | California | United States | 92701 |
| 15 | Innovative Clinical Research - Lafayette /ID# 208400 | Lafayette | Colorado | United States | 80026 |
| 16 | New England Research Associates, LLC /ID# 206896 | Bridgeport | Connecticut | United States | 06606-1827 |
| 17 | Ideal Clinical Research Inc. /ID# 209880 | Aventura | Florida | United States | 33180 |
| 18 | Skin Care Research, LLC /ID# 207099 | Boca Raton | Florida | United States | 33486-2269 |
| 19 | Midflorida Clinical Research, Inc. /ID# 213700 | Brandon | Florida | United States | 33511-5335 |
| 20 | Clinical Research of West Florida, Inc /ID# 206146 | Clearwater | Florida | United States | 33765 |
| 21 | Revival Research /ID# 208383 | Doral | Florida | United States | 33122-1902 |
| 22 | Universal Axon Clinical Research /ID# 213703 | Doral | Florida | United States | 33166 |
| 23 | Savin Medical Group, LLC /ID# 206902 | Miami Lakes | Florida | United States | 33014-2490 |
| 24 | Floridian Clinical Research /ID# 207433 | Miami Lakes | Florida | United States | 33016-1842 |
| 25 | Lakes Research, LLC /ID# 209156 | Miami | Florida | United States | 33014 |
| 26 | Miami Dade Medical Research Institute /ID# 209413 | Miami | Florida | United States | 33176 |
| 27 | Advanced Research for Health Improvement /ID# 217987 | Naples | Florida | United States | 34102-5430 |
| 28 | Advanced Research for Health Improvement /ID# 218003 | Naples | Florida | United States | 34102-5430 |
| 29 | Complete Health Research /ID# 213459 | Ormond Beach | Florida | United States | 32174-6302 |
| 30 | Precision Clinical Research /ID# 207364 | Sunrise | Florida | United States | 33351-7311 |
| 31 | Clinical Research Trials of Florida, Inc. /ID# 206840 | Tampa | Florida | United States | 33607 |
| 32 | ForCare Clinical Research /ID# 205120 | Tampa | Florida | United States | 33613-1244 |
| 33 | Georgia Pollens Clinical Research Centers, Inc /ID# 218567 | Albany | Georgia | United States | 31707-1282 |
| 34 | Marietta Dermatology Clinical Research /ID# 210317 | Marietta | Georgia | United States | 30060-1047 |
| 35 | Agile Clinical Research Trials /ID# 218080 | Sandy Springs | Georgia | United States | 30342 |
| 36 | Treasure Valley Medical Research /ID# 210298 | Boise | Idaho | United States | 83706 |
| 37 | Great Lakes Clinical Trials /ID# 205830 | Chicago | Illinois | United States | 60640 |
| 38 | Ashira Dermatology /ID# 205512 | Gurnee | Illinois | United States | 60031-3393 |
| 39 | Clinical Investigation Specialists, Inc. /ID# 206898 | Gurnee | Illinois | United States | 60031 |
| 40 | Northshore University Health System Dermatology Clinical Trials Unit /ID# 205135 | Skokie | Illinois | United States | 60077 |
| 41 | Raga Clinical Studies, LLC. /ID# 206749 | Crown Point | Indiana | United States | 46307 |
| 42 | Hutchinson Clinic /ID# 205970 | Hutchinson | Kansas | United States | 67502-1131 |
| 43 | Continental Clinical Solutions /ID# 210327 | Towson | Maryland | United States | 21204 |
| 44 | Beacon Clinical Research, LLC /ID# 206894 | Quincy | Massachusetts | United States | 02169 |
| 45 | David Fivenson, MD, PLC /ID# 206903 | Ann Arbor | Michigan | United States | 48103 |
| 46 | University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 206895 | Ann Arbor | Michigan | United States | 48109 |
| 47 | Allergy, Asthma & Immunology Associates, PC /ID# 218169 | Lincoln | Nebraska | United States | 68505-2343 |
| 48 | Skin Specialists, PC /ID# 205515 | Omaha | Nebraska | United States | 68144 |
| 49 | Duplicate_Summit Medical Group /ID# 213863 | Clifton | New Jersey | United States | 07012-1647 |
| 50 | Skin Laser and Surgery Specialists of NY and NJ /ID# 206754 | Hackensack | New Jersey | United States | 07601-1997 |
| 51 | Care Access Research /ID# 218476 | Hoboken | New Jersey | United States | 07030-2757 |
| 52 | University of New Mexico School of Medicine /ID# 206756 | Albuquerque | New Mexico | United States | 87131-0001 |
| 53 | Fordham Dermatology /ID# 218508 | Bronx | New York | United States | 10458-5046 |
| 54 | PMG Research of Wilmington LLC /ID# 205968 | Wilmington | North Carolina | United States | 28401 |
| 55 | University Hospitals Case Medical Center /ID# 206639 | Cleveland | Ohio | United States | 44106 |
| 56 | Awasty Research Network, LLC /ID# 206748 | Marion | Ohio | United States | 43302-6225 |
| 57 | Southside Dermatology /ID# 214451 | Tulsa | Oklahoma | United States | 74132 |
| 58 | Vital Prospects Clinical Research Institute, PC /ID# 205824 | Tulsa | Oklahoma | United States | 74136-7049 |
| 59 | Cyn3rgy Research /ID# 218064 | Gresham | Oregon | United States | 97030-8316 |
| 60 | Velocity Clinical Research Hallandale Beach /ID# 207544 | Medford | Oregon | United States | 97504 |
| 61 | Clinical Research Solutions, LLC /ID# 218416 | Jackson | Tennessee | United States | 38305-2163 |
| 62 | Stones River Dermatology /ID# 205178 | Murfreesboro | Tennessee | United States | 37129-3194 |
| 63 | Metroplex Dermatology /ID# 213307 | Arlington | Texas | United States | 76014-3105 |
| 64 | Bellaire Dermatology /ID# 205470 | Bellaire | Texas | United States | 77401 |
| 65 | Center for Clinical Studies /ID# 213186 | Cypress | Texas | United States | 77433 |
| 66 | Dermatology Treatment and Research Center, PA /ID# 205473 | Dallas | Texas | United States | 75230 |
| 67 | Epiphany Dermatology - Fort Worth /ID# 210073 | Fort Worth | Texas | United States | 76244-6548 |
| 68 | Styde Research, LLC /ID# 213469 | Lewisville | Texas | United States | 75067 |
| 69 | Austin Institute for Clinical Research /ID# 206640 | Pflugerville | Texas | United States | 78660 |
| 70 | Derm Clin Res Ctr San Antonio /ID# 205469 | San Antonio | Texas | United States | 78229 |
| 71 | EPIC Medical Research /ID# 206382 | Murray | Utah | United States | 84123-5632 |
| 72 | Aspen Clinical Research /ID# 208399 | Orem | Utah | United States | 84058 |
| 73 | Timber Lane Allergy & Asthma Research, LLC /ID# 206897 | South Burlington | Vermont | United States | 05403-7204 |
| 74 | The Education & Research Foundation, Inc. /ID# 206900 | Lynchburg | Virginia | United States | 24501-1403 |
| 75 | Bellingham Asthma Allergy and Immunology Clinic /ID# 210357 | Bellingham | Washington | United States | 98225-1945 |
| 76 | Clinical Investigation Specialist, Inc - Kenosha /ID# 215933 | Kenosha | Wisconsin | United States | 53144-1782 |
| 77 | The Skin Hospital /ID# 217846 | Westmead | New South Wales | Australia | 2145 |
| 78 | The Skin Centre /ID# 205922 | Benowa | Queensland | Australia | 4217 |
| 79 | Box Hill Hospital /ID# 206023 | Box Hill | Victoria | Australia | 3128 |
| 80 | Monash Children's Hospital /ID# 217917 | Clayton | Victoria | Australia | 3168 |
| 81 | Sinclair Dermatology /ID# 217791 | East Melbourne | Victoria | Australia | 3002 |
| 82 | The Royal Melbourne Hospital /ID# 205919 | Parkville | Victoria | Australia | 3050 |
| 83 | Murdoch Children's Research Institute /ID# 205667 | Parkville | Victoria | Australia | 3052 |
| 84 | Universitaetsklinikum St. Poelten /ID# 206909 | Sankt Poelten | Niederoesterreich | Austria | 3100 |
| 85 | Ordensklinikum Linz GmbH Elisabethinen /ID# 206573 | Linz | Oberoesterreich | Austria | 4010 |
| 86 | Klinik Donaustadt /ID# 206572 | Vienna | Wien | Austria | 1220 |
| 87 | Landeskrankenhaus Salzburg-Universitätsklinikum der PMU (LKH) /ID# 208281 | Salzburg | Austria | 5020 | |
| 88 | UCL Saint-Luc /ID# 205537 | Woluwe-Saint-Lambert | Bruxelles-Capitale | Belgium | 1200 |
| 89 | UZ Gent /ID# 205181 | Gent | Oost-Vlaanderen | Belgium | 9000 |
| 90 | Centre Hospitalier Universitaire du Sart Tilman CHU de Liege /ID# 204938 | Liege | Belgium | 4000 | |
| 91 | Medical center Sveti Panteleimon /ID# 210414 | Sofia | Bulgaria | 1000 | |
| 92 | Acibadem City Clinic Tokuda University Hospital EAD /ID# 205292 | Sofia | Bulgaria | 1407 | |
| 93 | Military Medical Academy Multiprofile Hospital /ID# 205291 | Sofia | Bulgaria | 1606 | |
| 94 | Medical complex Doverie /ID# 211289 | Sofia | Bulgaria | 1632 | |
| 95 | Stratica Medical /ID# 205415 | Edmonton | Alberta | Canada | T5K 1X3 |
| 96 | Alberta DermaSurgery Centre /ID# 205422 | Edmonton | Alberta | Canada | T6G 1C3 |
| 97 | UBC Department of Dermatology and Skin Science The Skin Care Centre /ID# 207837 | Vancouver | British Columbia | Canada | V5Z 4E8 |
| 98 | Pacific Derm /ID# 206797 | Vancouver | British Columbia | Canada | V6H 4E1 |
| 99 | Skin Care Studio /ID# 205420 | St. John's | Newfoundland and Labrador | Canada | A1E 1V4 |
| 100 | SimcoDerm Medical and Surgical Dermatology Center /ID# 206333 | Barrie | Ontario | Canada | L4M 7G1 |
| 101 | Kingsway Clinical Research /ID# 206005 | Etobicoke | Ontario | Canada | M8X 1Y9 |
| 102 | Dr. Dusan Sajic Medicine Professional Corporation /ID# 206890 | Guelph | Ontario | Canada | N1L 0B7 |
| 103 | The Guenther Dermatology Research Centre /ID# 206772 | London | Ontario | Canada | N6A 3H7 |
| 104 | DermEdge Research Inc. /ID# 206036 | Mississauga | Ontario | Canada | L5H 1G9 |
| 105 | Dr. S.K. Siddha Medicine Professional Corporation /ID# 207138 | Newmarket | Ontario | Canada | L3Y 5G8 |
| 106 | Allergy Research Canada Inc. /ID# 213547 | Niagara Falls | Ontario | Canada | L2H 1H5 |
| 107 | Dr. Lyne Giroux Medicine Professional Corporation /ID# 206771 | Sudbury | Ontario | Canada | P3C 1X8 |
| 108 | Niakosari Medicine Professional Corporation /ID# 206004 | Toronto | Ontario | Canada | M2M 4J5 |
| 109 | Skinsense Medical Research /ID# 206873 | Saskatoon | Saskatchewan | Canada | S7K 0H6 |
| 110 | DermaPlus - Poliklinika za dermatologiju i venerologiju /ID# 205429 | Zagreb | Grad Zagreb | Croatia | 10000 |
| 111 | Djecja bolnica Srebrnjak /ID# 205926 | Zagreb | Grad Zagreb | Croatia | 10000 |
| 112 | Poliklinika Vlatka Cavka d.o.o. /ID# 211126 | Zagreb | Grad Zagreb | Croatia | 10000 |
| 113 | Naftalan - Specijalna bolnica za medicinsku rehabilitaciju /ID# 203448 | Ivanic-Grad | Zagrebacka Zupanija | Croatia | 10310 |
| 114 | Fakultni nemocnice Plzen /ID# 205096 | Plzen | Czechia | 305 99 | |
| 115 | Sanatorium profesora Arenbergera /ID# 205098 | Praha | Czechia | 110 00 | |
| 116 | Vseobecna fakultni nemocnice v Praze /ID# 205201 | Praha | Czechia | 128 08 | |
| 117 | Fakultni Nemocnice v Motole /ID# 218192 | Praha | Czechia | 150 06 | |
| 118 | Krajska zdravotni, a.s. - Masarykova nemocnice v Usti nad Labem, o. z. /ID# 205097 | Usti nad Labem | Czechia | 400 11 | |
| 119 | Aarhus University Hospital /ID# 205524 | Aarhus N | Midtjylland | Denmark | 8200 |
| 120 | Sjællands Universitetshospital /ID# 205960 | Roskilde | Sjælland | Denmark | 4000 |
| 121 | Hopital Prive d'Antony /ID# 206553 | Antony | Ile-de-France | France | 92160 |
| 122 | Hopital Saint-Andre /ID# 206554 | Bordeaux | France | 33075 | |
| 123 | CHRU de Brest - Hopital Morvan /ID# 206555 | Brest | France | 29200 | |
| 124 | C.H. de Bretagne Sud /ID# 206910 | Lorient | France | 56322 | |
| 125 | AP-HP - Hopital Saint-Louis /ID# 206552 | Paris | France | 75010 | |
| 126 | Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 206658 | Kiel | Schleswig-Holstein | Germany | 24105 |
| 127 | Klinikum Darmstadt /ID# 207483 | Darmstadt | Germany | 64283 | |
| 128 | Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 205767 | Dresden | Germany | 01307 | |
| 129 | Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 207982 | Hamburg | Germany | 20246 | |
| 130 | Dermatologische Gemeinschaftspraxis Mahlow /ID# 205765 | Mahlow | Germany | 15831 | |
| 131 | Haut- und Laserzentrum Hunsrück /ID# 205768 | Simmern | Germany | 55469 | |
| 132 | Hautarztpraxis Dr. med. Matthias Hoffmann /ID# 205766 | Witten | Germany | 58453 | |
| 133 | CentroDerm GmbH /ID# 206861 | Wuppertal | Germany | 42287 | |
| 134 | 251 Airforce General Hospital /ID# 205841 | Athens | Attiki | Greece | 11525 |
| 135 | 401 GSNA - 401 Army General Hospital /ID# 205352 | Athens | Attiki | Greece | 11525 |
| 136 | General Hospital Andreas Syggros /ID# 204527 | Athens | Attiki | Greece | 16121 |
| 137 | Papageorgiou General Hospital Thessaloniki /ID# 204526 | Stavroupoli (Thessalonikis) | Thessaloniki | Greece | 55536 |
| 138 | Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz /ID# 218072 | Miskolc | Borsod-Abauj-Zemplen | Hungary | 3526 |
| 139 | Bugat Pal Korhaz /ID# 211247 | Gyöngyös | Heves | Hungary | 3200 |
| 140 | Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 205611 | Kaposvár | Somogy | Hungary | 7400 |
| 141 | Drug Research Center /ID# 217855 | Balatonfured | Veszprem | Hungary | 8230 |
| 142 | Clinexpert Kft /ID# 211246 | Budapest | Hungary | 1033 | |
| 143 | Synexus Magyarorszag Kft. /ID# 206008 | Budapest | Hungary | 1036 | |
| 144 | Pecsi Tudomanyegyetem Klinikai Kozpont /ID# 205085 | Pecs | Hungary | 7624 | |
| 145 | St James Hospital /ID# 204264 | Dublin 8 | Dublin | Ireland | D08 NHY1 |
| 146 | South Infirmary Victoria University Hospital /ID# 204265 | Cork | Ireland | T12 X23H | |
| 147 | University Hospital Galway /ID# 209965 | Galway | Ireland | H91 YR71 | |
| 148 | University Hospital Waterford /ID# 204266 | Waterford | Ireland | X91 ER8E | |
| 149 | IRCCS Istituti Fisioterapici Ospitalieri-Istituto Dermatologico San Gallicano /ID# 205986 | Rome | Lazio | Italy | 00144 |
| 150 | Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 205987 | Rome | Lazio | Italy | 00168 |
| 151 | ASST Spedali civili di Brescia /ID# 205927 | Brescia | Italy | 25123 | |
| 152 | Azienda Ospedaliero Universitaria di Cagliari- Presidio Ospedaliero /ID# 205168 | Cagliari | Italy | 09124 | |
| 153 | Presidio Ospedaliero San Salvatore /ID# 205167 | L'Aquila | Italy | 67100 | |
| 154 | Azienda Ospedaliero-Universitaria di Modena /ID# 205169 | Modena | Italy | 41124 | |
| 155 | Korea University Ansan Hospital /ID# 206342 | Ansan | Gyeonggido | Korea, Republic of | 15355 |
| 156 | SoonChunHyang University Buchon Hospital /ID# 206391 | Buncheon | Gyeonggido | Korea, Republic of | 14584 |
| 157 | Ajou University Hospital /ID# 206341 | Suwon | Gyeonggido | Korea, Republic of | 16499 |
| 158 | The Catholic University of Korea Incheon St.Mary's Hospital /ID# 206529 | Incheon | Korea, Republic of | 21431 | |
| 159 | Seoul National University Hospital /ID# 206396 | Seoul | Korea, Republic of | 03080 | |
| 160 | Chung-Ang University Hostipal /ID# 206397 | Seoul | Korea, Republic of | 06973 | |
| 161 | Hallym University Kangnam Sacred Heart Hospital /ID# 206343 | Seoul | Korea, Republic of | 07441 | |
| 162 | Bravis Ziekenhuis /ID# 206676 | Bergen op Zoom | Noord-Brabant | Netherlands | 4624 VT |
| 163 | Centrum Oosterwal /ID# 209640 | Alkmaar | Netherlands | 1817 MS | |
| 164 | Reinier de Graaf /ID# 205811 | Delft | Netherlands | 2625 AD | |
| 165 | Universitair Medisch Centrum Groningen /ID# 205162 | Groningen | Netherlands | 9713 GZ | |
| 166 | Greenlane Clinical Centre /ID# 205664 | Epsom | Auckland | New Zealand | 1051 |
| 167 | CCA Braga - Hospital de Braga /ID# 205854 | Braga | Portugal | 4710-243 | |
| 168 | Centro Hospitalar de Leiria, EPE /ID# 209906 | Leiria | Portugal | 2410-197 | |
| 169 | Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital de Santa Maria /ID# 205839 | Lisboa | Portugal | 1649-035 | |
| 170 | Hospital CUF Descobertas /ID# 205431 | Lisboa | Portugal | 1998-018 | |
| 171 | CHP, EPE- Hospital Geral de Sa /ID# 205187 | Porto | Portugal | 4050 | |
| 172 | Centro Hospitalar Universitario de Sao Joao, EPE /ID# 205679 | Porto | Portugal | 4200-319 | |
| 173 | National Skin Centre /ID# 205222 | Singapore | Central Singapore | Singapore | 308205 |
| 174 | National University Hospital /ID# 205224 | Singapore | Singapore | 119074 | |
| 175 | Singapore General Hospital /ID# 205225 | Singapore | Singapore | 169608 | |
| 176 | KK Women's & Children Hospital /ID# 206693 | Singapore | Singapore | 229899 | |
| 177 | Changi General Hospital /ID# 205223 | Singapore | Singapore | 529889 | |
| 178 | Hospital Vital Alvarez Buylla /ID# 205770 | Mieres | Asturias | Spain | 33611 |
| 179 | Hospital Sant Joan de Deu /ID# 218047 | Esplugues de Llobregat | Barcelona | Spain | 08950 |
| 180 | Hospital Parc de Salut del Mar /ID# 204709 | Barcelona | Spain | 08003 | |
| 181 | Hospital Clinic de Barcelona /ID# 210564 | Barcelona | Spain | 08036 | |
| 182 | Hospital Universitario Reina Sofia /ID# 204712 | Cordoba | Spain | 14004 | |
| 183 | Hospital Campus de la Salud /ID# 205544 | Granada | Spain | 18016 | |
| 184 | Hospital General Universitario Gregorio Maranon /ID# 204380 | Madrid | Spain | 28007 | |
| 185 | Hospital Infantil Universitario Nino Jesus /ID# 210437 | Madrid | Spain | 28009 | |
| 186 | Hospital Universitario Infanta Leonor /ID# 204710 | Madrid | Spain | 28031 | |
| 187 | Hospital General Universitario de Valencia /ID# 210565 | Valencia | Spain | 46014 | |
| 188 | Taipei Medical University Shuang Ho Hospital /ID# 204804 | New Taipei City | Taiwan | 23561 | |
| 189 | Chung Shan Medical University Hospital /ID# 205092 | Taichung | Taiwan | 40201 | |
| 190 | National Taiwan University Hospital /ID# 204803 | Taipei City | Taiwan | 100 | |
| 191 | Linkou Chang Gung Memorial Ho /ID# 204783 | Taoyuan City | Taiwan | 333 | |
| 192 | University Hospital Southampton NHS Foundation Trust /ID# 205711 | Southampton | Hampshire | United Kingdom | SO16 6YD |
| 193 | Northwick Park Hospital /ID# 205250 | Middlesex | Harrow | United Kingdom | HA1 3UJ |
| 194 | Barts Health NHS Trust /ID# 206491 | London | London, City Of | United Kingdom | E1 2ES |
| 195 | The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 204993 | Newcastle Upon Tyne | United Kingdom | NE7 7DN | |
| 196 | University Hospital Plymouth NHS Trust /ID# 204649 | Plymouth | United Kingdom | PL6 8DH |
Sponsors and Collaborators
- AbbVie
Investigators
- Study Director: ABBVIE INC., AbbVie
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT03607422
Other Study ID Numbers:
- M18-891
- 2018-001383-28
First Posted:
Jul 31, 2018
Last Update Posted:
Mar 28, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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
Keywords provided by AbbVie
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at 154 study sites in 23 countries across Europe, North America, Oceania, and the Asia-Pacific region. The study included a 16-week double-blind treatment period followed by an ongoing blinded extension period. The first 836 adults and adolescents enrolled constituted the Main Study; additional adolescents were enrolled in the Adolescent Substudy to ensure enrollment of a total of 180 adolescent participants overall. Results are reported up to Week 16. |
|---|---|
| Pre-assignment Detail | Participants were randomized equally into 1 of 3 treatment groups, stratified by disease severity (validated Investigator Global Assessment Scale for Atopic Dermatitis [vIGA-AD] moderate [3] vs severe [4]), geographic region (US/Puerto Rico/Canada vs Other), and age (adolescent [ages 12 to 17] vs adult [ages 18 to 75]). Randomization for the adolescent substudy was stratified by disease severity (vIGA-AD 3 vs vIGA-AD 4) and geographic region (US/Puerto Rico/Canada vs Other). |
| Arm/Group Title | Adults: Placebo | Adults: Upadacitinib 15 mg QD | Adults: Upadacitinib 30 mg QD | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants ≥ 18 years old received placebo orally once a day (QD) for 16 weeks. | Participants ≥ 18 years old received upadacitinib 15 mg orally once a day for 16 weeks. | Participants ≥ 18 years old received upadacitinib 30 mg orally once a day for 16 weeks. | Adolescent participants (12 - 17 years old) received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Period Title: Overall Study | ||||||
| STARTED | 242 | 243 | 247 | 60 | 58 | 62 |
| COMPLETED | 204 | 233 | 235 | 55 | 55 | 59 |
| NOT COMPLETED | 38 | 10 | 12 | 5 | 3 | 3 |
Baseline Characteristics
| Arm/Group Title | Adults: Placebo | Adults: Upadacitinib 15 mg QD | Adults: Upadacitinib 30 mg QD | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants ≥ 18 years old received placebo orally once a day for 16 weeks. | Participants ≥ 18 years old received upadacitinib 15 mg orally once a day for 16 weeks. | Participants ≥ 18 years old received upadacitinib 30 mg orally once a day for 16 weeks. | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. | Total of all reporting groups |
| Overall Participants | 242 | 243 | 247 | 60 | 58 | 62 | 912 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
36.0
(14.08)
|
35.7
(15.15)
|
36.7
(15.36)
|
15.5
(1.67)
|
15.2
(1.79)
|
15.8
(1.70)
|
32.1
(15.66)
|
| Age, Customized (Count of Participants) | |||||||
| 12 - 14 years |
0
0%
|
0
0%
|
0
0%
|
18
30%
|
23
39.7%
|
15
24.2%
|
56
6.1%
|
| 15 - 17 years |
0
0%
|
0
0%
|
0
0%
|
42
70%
|
35
60.3%
|
47
75.8%
|
124
13.6%
|
| 18 - < 40 years |
161
66.5%
|
165
67.9%
|
161
65.2%
|
0
0%
|
0
0%
|
0
0%
|
487
53.4%
|
| 40 - < 65 years |
70
28.9%
|
63
25.9%
|
67
27.1%
|
0
0%
|
0
0%
|
0
0%
|
200
21.9%
|
| ≥ 65 years |
11
4.5%
|
15
6.2%
|
19
7.7%
|
0
0%
|
0
0%
|
0
0%
|
45
4.9%
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
104
43%
|
102
42%
|
103
41.7%
|
35
58.3%
|
38
65.5%
|
26
41.9%
|
408
44.7%
|
| Male |
138
57%
|
141
58%
|
144
58.3%
|
25
41.7%
|
20
34.5%
|
36
58.1%
|
504
55.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||
| Hispanic or Latino |
25
10.3%
|
18
7.4%
|
17
6.9%
|
10
16.7%
|
12
20.7%
|
11
17.7%
|
93
10.2%
|
| Not Hispanic or Latino |
217
89.7%
|
225
92.6%
|
230
93.1%
|
50
83.3%
|
46
79.3%
|
51
82.3%
|
819
89.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||||
| American Indian or Alaska Native |
5
2.1%
|
4
1.6%
|
1
0.4%
|
0
0%
|
2
3.4%
|
1
1.6%
|
13
1.4%
|
| Asian |
52
21.5%
|
62
25.5%
|
55
22.3%
|
6
10%
|
5
8.6%
|
12
19.4%
|
192
21.1%
|
| Native Hawaiian or Other Pacific Islander |
1
0.4%
|
0
0%
|
0
0%
|
1
1.7%
|
2
3.4%
|
0
0%
|
4
0.4%
|
| Black or African American |
15
6.2%
|
16
6.6%
|
17
6.9%
|
7
11.7%
|
5
8.6%
|
3
4.8%
|
63
6.9%
|
| White |
165
68.2%
|
160
65.8%
|
172
69.6%
|
45
75%
|
42
72.4%
|
46
74.2%
|
630
69.1%
|
| More than one race |
4
1.7%
|
1
0.4%
|
2
0.8%
|
1
1.7%
|
2
3.4%
|
0
0%
|
10
1.1%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Study Enrollment (Count of Participants) | |||||||
| Main Study |
242
100%
|
243
100%
|
247
100%
|
36
60%
|
33
56.9%
|
35
56.5%
|
836
91.7%
|
| Adolescent Substudy |
0
0%
|
0
0%
|
0
0%
|
24
40%
|
25
43.1%
|
27
43.5%
|
76
8.3%
|
| Geographic Region (Count of Participants) | |||||||
| US/Puerto Rico/Canada |
95
39.3%
|
95
39.1%
|
99
40.1%
|
25
41.7%
|
24
41.4%
|
27
43.5%
|
365
40%
|
| Other |
147
60.7%
|
148
60.9%
|
148
59.9%
|
35
58.3%
|
34
58.6%
|
35
56.5%
|
547
60%
|
| vIGA-AD (Count of Participants) | |||||||
| 3 (Moderate) |
110
45.5%
|
111
45.7%
|
111
44.9%
|
26
43.3%
|
27
46.6%
|
29
46.8%
|
414
45.4%
|
| 4 (Severe) |
132
54.5%
|
132
54.3%
|
136
55.1%
|
34
56.7%
|
31
53.4%
|
33
53.2%
|
498
54.6%
|
| Eczema Area and Severity Index (EASI) Score (score on a scale) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [score on a scale] |
28.74
(11.865)
|
28.65
(11.633)
|
29.61
(12.030)
|
30.12
(13.263)
|
28.01
(12.216)
|
31.15
(13.998)
|
29.16
(12.112)
|
| Disease Duration since Diagnosis (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
22.263
(14.0798)
|
19.802
(13.8089)
|
21.911
(14.8401)
|
12.169
(4.7104)
|
11.184
(4.5479)
|
12.128
(4.6414)
|
19.452
(13.4892)
|
Outcome Measures
| Title | Main Study: Percentage of Participants Achieving at Least a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) From Baseline at Week 16 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population for the main study (ITT_M) includes all participants who were randomized in the main study (adults and adolescents). Non-responder imputation incorporating multiple imputation to handle missing data due to coronavirus disease 2019 pandemic (COVID-19) (NRI-C) was used. The pre-specified primary analysis included participants enrolled in the main study only; Efficacy analyses of adolescent participants were conducted separately and are reported below. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 278 | 276 | 282 |
| Number (95% Confidence Interval) [percentage of participants] |
13.3
5.5%
|
60.1
24.7%
|
72.9
29.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 59.6 | |
| Confidence Interval |
(2-Sided) 95% 53.1 to 66.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 46.9 | |
| Confidence Interval |
(2-Sided) 95% 39.9 to 53.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16 |
|---|---|
| Description | The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale: 0 - Clear: No inflammatory signs of AD; 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification, no oozing or crusting; 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification, no oozing or crusting; 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, oozing or crusting may be present; 4 - Severe: Marked erythema, induration/papulation and/or lichenification; Oozing or crusting may be present. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 278 | 276 | 282 |
| Number (95% Confidence Interval) [percentage of participants] |
4.7
1.9%
|
38.8
16%
|
52.0
21.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 47.4 | |
| Confidence Interval |
(2-Sided) 95% 41.0 to 53.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 34.0 | |
| Confidence Interval |
(2-Sided) 95% 27.8 to 40.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus Numerical Rating Scale (NRS) at Week 16 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 274 | 270 | 280 |
| Number (95% Confidence Interval) [percentage of participants] |
9.1
3.8%
|
41.9
17.2%
|
59.6
24.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 50.4 | |
| Confidence Interval |
(2-Sided) 95% 43.8 to 57.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 32.6 | |
| Confidence Interval |
(2-Sided) 95% 25.8 to 39.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a 90% Reduction From Baseline in EASI Score (EASI 90) at Week 16 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 278 | 276 | 282 |
| Number (95% Confidence Interval) [percentage of participants] |
5.4
2.2%
|
42.4
17.4%
|
58.5
23.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 53.1 | |
| Confidence Interval |
(2-Sided) 95% 46.7 to 59.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 36.9 | |
| Confidence Interval |
(2-Sided) 95% 30.6 to 43.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 274 | 270 | 280 |
| Number (95% Confidence Interval) [percentage of participants] |
3.6
1.5%
|
48.9
20.1%
|
60.7
24.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 57.0 | |
| Confidence Interval |
(2-Sided) 95% 50.9 to 63.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 45.2 | |
| Confidence Interval |
(2-Sided) 95% 38.9 to 51.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving an EASI 75 Response at Week 2 |
|---|---|
| Description | 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. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score. |
| Time Frame | Baseline and Week 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 278 | 276 | 282 |
| Number (95% Confidence Interval) [percentage of participants] |
3.6
1.5%
|
33.0
13.6%
|
44.0
17.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 40.4 | |
| Confidence Interval |
(2-Sided) 95% 34.2 to 46.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 29.4 | |
| Confidence Interval |
(2-Sided) 95% 23.5 to 35.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 274 | 270 | 280 |
| Number (95% Confidence Interval) [percentage of participants] |
0.7
0.3%
|
7.4
3%
|
15.7
6.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 14.9 | |
| Confidence Interval |
(2-Sided) 95% 10.6 to 19.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 6.7 | |
| Confidence Interval |
(2-Sided) 95% 3.4 to 10.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 2 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11- point scale from 0 (no itch) to 10 (worst imaginable itch). The percentage of participants who had a 4-point or greater improvement from Baseline in Worst Pruritus NRS score at Day 2 was pre-specified as a ranked secondary endpoint for participants in the upadacitinib 30 mg group versus placebo group only. |
| Time Frame | Baseline and Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 (NRI-NC) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 267 | 269 | 278 |
| Number (95% Confidence Interval) [percentage of participants] |
0.7
0.3%
|
7.4
3%
|
7.9
3.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 7.2 | |
| Confidence Interval |
(2-Sided) 95% 3.8 to 10.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 3 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). The percentage of participants who had a 4-point or greater improvement in Worst Pruritus NRS score from Baseline at Day 3 was pre-specified as a ranked secondary endpoint for participants in the upadacitinib 15 mg group versus placebo group only. |
| Time Frame | Baseline and Day 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 (NRI-NC) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 267 | 269 | 278 |
| Number (95% Confidence Interval) [percentage of participants] |
3.0
1.2%
|
11.5
4.7%
|
17.3
7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 8.6 | |
| Confidence Interval |
(2-Sided) 95% 4.3 to 12.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Experiencing a Flare During the Double-blind Treatment Period |
|---|---|
| Description | A flare, characterized as a clinically meaningful worsening in EASI, is defined as an increase in EASI score of ≥ 6.6 points from Baseline during the double-blind treatment period and prior to use of any rescue medication. Flare was assessed in participants with an EASI score of 65.4 or less at Baseline. |
| Time Frame | From first dose of study drug to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with an EASI score ≤ 65.4 at Baseline and at least one EASI post-baseline assessment prior to use of rescue medication. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 269 | 274 | 277 |
| Number (95% Confidence Interval) [percentage of participants] |
24.5
10.1%
|
2.2
0.9%
|
1.4
0.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | -23.1 | |
| Confidence Interval |
(2-Sided) 95% -28.4 to -17.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | -22.4 | |
| Confidence Interval |
(2-Sided) 95% -27.8 to -16.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 12 Points From Baseline in Atopic Dermatitis Impact Scale (ADerm-IS) Sleep Domain Score at Week 16 |
|---|---|
| Description | The ADerm-IS is a 10-item patient reported outcome (PRO) questionnaire designed to assess a variety of impacts that participants experience from their AD. The ADerm-IS sleep domain consists of 3 questions designed to assess the impact of AD on sleep on a daily basis over a 24-hour recall period. The items include difficulty falling asleep, impact on sleep, and waking at night. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The ADerm-IS sleep domain score is the sum of the 3 item scores and ranges from 0 (no impact) to 30 (worst impact). The ADerm-IS sleep domain was analyzed based on weekly rolling averages of daily scores. The minimal clinically important difference for ADerm-IS sleep domain score is 12. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with ADerm-IS Sleep Domain score ≥ 12 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 233 | 219 | 228 |
| Number (95% Confidence Interval) [percentage of participants] |
12.4
5.1%
|
50.2
20.7%
|
62.3
25.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 49.8 | |
| Confidence Interval |
(2-Sided) 95% 42.2 to 57.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 37.9 | |
| Confidence Interval |
(2-Sided) 95% 30.1 to 45.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain Score at Week 16 |
|---|---|
| Description | The ADerm-SS is an 11-item PRO questionnaire designed to assess signs and symptoms that patients may experience due to AD using a 24-hour recall period. For the skin pain item participants were asked on a daily basis to indicate how bad their worst skin pain due to AD was in the past 24 hours on an NRS from 0 (no pain) to 10 (worst imaginable pain). The ADerm-SS skin pain score was analyzed using weekly rolling averages of daily scores. The minimal clinically important difference for ADerm-SS skin pain score is 4. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with ADerm-SS Skin Pain Score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 247 | 237 | 238 |
| Number (95% Confidence Interval) [percentage of participants] |
13.4
5.5%
|
49.4
20.3%
|
65.1
26.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 51.8 | |
| Confidence Interval |
(2-Sided) 95% 44.4 to 59.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 35.9 | |
| Confidence Interval |
(2-Sided) 95% 28.2 to 43.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 28 Points From Baseline in ADerm-SS 7-Item Total Symptom Score (TSS-7) at Week 16 |
|---|---|
| Description | The ADerm-SS is an 11-item questionnaire designed to assess signs and symptoms that participants may experience due to AD using a 24-hour recall period. The 7-item total symptom score includes 7 symptoms (items 1-7 of the ADerm-SS), each assessed on a NRS from 0 (no symptom) to 10 (worst imaginable). The 7 symptoms included in the score are itch while asleep, itch while awake, skin pain (each assessed daily), skin cracking, skin cracking pain, dry skin, and skin flaking (assessed weekly). The TSS-7 score ranges from 0 to 70, with higher scores indicating worsening symptoms. The minimal clinically important difference for ADerm-SS TSS-7 is 28. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with ADerm-SS TSS-7 ≥ 28 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 244 | 230 | 234 |
| Number (95% Confidence Interval) [percentage of participants] |
12.7
5.2%
|
53.0
21.8%
|
66.2
26.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 53.3 | |
| Confidence Interval |
(2-Sided) 95% 46.0 to 60.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 40.3 | |
| Confidence Interval |
(2-Sided) 95% 32.7 to 48.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 11 Points From Baseline in ADerm-IS Emotional State Domain Score at Week 16 |
|---|---|
| Description | The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD. ADerm-IS emotional state sums three items [Items 8-10] measuring self-consciousness, embarrassment, and sadness with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The emotional state domain score ranges from 0 to 30, where higher scores represent worst impact. The minimal clinically important difference for ADerm-IS emotional state domain score is 11. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with ADerm-IS Emotional State domain score ≥ 11 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 234 | 228 | 228 |
| Number (95% Confidence Interval) [percentage of participants] |
16.7
6.9%
|
57.0
23.5%
|
71.5
28.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 54.8 | |
| Confidence Interval |
(2-Sided) 95% 47.2 to 62.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 40.3 | |
| Confidence Interval |
(2-Sided) 95% 32.3 to 48.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 14 Points From Baseline in ADerm-IS Daily Activities Domain Score at Week 16 |
|---|---|
| Description | The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD. ADerm-IS Daily Activities sums four items measuring limitations of household, physical, and social activities, and difficulty concentrating with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The daily activities domain score ranges from 0 to 40, where higher scores represent worst impact. The minimal clinically important difference for the ADerm-IS daily activities domain score is 14. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with ADerm-IS Daily Activities Domain Score ≥ 14 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 227 | 207 | 223 |
| Number (95% Confidence Interval) [percentage of participants] |
18.9
7.8%
|
57.0
23.5%
|
69.5
28.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 50.6 | |
| Confidence Interval |
(2-Sided) 95% 42.8 to 58.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 37.9 | |
| Confidence Interval |
(2-Sided) 95% 29.5 to 46.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a 100% Reduction From Baseline in EASI Score (EASI 100) at Week 16 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 278 | 276 | 282 |
| Number (95% Confidence Interval) [percentage of participants] |
0.7
0.3%
|
14.1
5.8%
|
18.8
7.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 18.1 | |
| Confidence Interval |
(2-Sided) 95% 13.5 to 22.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 13.4 | |
| Confidence Interval |
(2-Sided) 95% 9.2 to 17.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percent Change From Baseline in Worst Pruritus NRS at Week 16 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores. A negative change from Baseline indicates improvement. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements (MMRM) including observed measurements at all visits, except that measurements after any rescue medication were excluded. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 119 | 224 | 235 |
| Least Squares Mean (95% Confidence Interval) [percent change] |
-17.04
|
-51.20
|
-66.49
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model. | |
| Method of Estimation | Estimation Parameter | Least Squares (LS) Mean Difference |
| Estimated Value | -49.45 | |
| Confidence Interval |
(2-Sided) 95% -56.05 to -42.84 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.364 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -34.16 | |
| Confidence Interval |
(2-Sided) 95% -40.81 to -27.51 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.386 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percent Change From Baseline in EASI Score at Week 16 |
|---|---|
| Description | 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 Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements (MMRM) including observed measurements at all visits, except that measurements after any rescue medication were excluded. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 142 | 246 | 250 |
| Least Squares Mean (95% Confidence Interval) [percent change] |
-34.51
|
-74.13
|
-84.65
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -50.14 | |
| Confidence Interval |
(2-Sided) 95% -56.28 to -44.00 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.127 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -39.62 | |
| Confidence Interval |
(2-Sided) 95% -45.79 to -33.46 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 3.139 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Patient Oriented Eczema Measure (POEM) Total Score at Week 16 |
|---|---|
| Description | The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults. Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema). A change in POEM score of 3.4 points is considered the minimal clinically important difference. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with POEM score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 268 | 268 | 269 |
| Number (95% Confidence Interval) [percentage of participants] |
28.7
11.9%
|
70.9
29.2%
|
83.5
33.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 54.7 | |
| Confidence Interval |
(2-Sided) 95% 47.7 to 61.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 42.1 | |
| Confidence Interval |
(2-Sided) 95% 34.5 to 49.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 |
|---|---|
| Description | The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. 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 are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. the DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study who were ≥ 16 years old at Screening with DLQI score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 250 | 251 | 251 |
| Number (95% Confidence Interval) [percentage of participants] |
28.4
11.7%
|
71.7
29.5%
|
77.6
31.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 49.0 | |
| Confidence Interval |
(2-Sided) 95% 41.4 to 56.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 42.8 | |
| Confidence Interval |
(2-Sided) 95% 35.0 to 50.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements (MMRM) including observed measurements at all visits, except that measurements after any rescue medication were excluded. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 136 | 245 | 241 |
| Least Squares Mean (95% Confidence Interval) [percent change] |
-28.43
|
-57.90
|
-68.44
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -40.01 | |
| Confidence Interval |
(2-Sided) 95% -45.80 to -34.22 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.949 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, Baseline vIGA-AD category and age in the model. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -29.47 | |
| Confidence Interval |
(2-Sided) 95% -35.24 to -23.69 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.941 |
|
| Estimation Comments | ||
| Title | Main Study: Percentage of Participants Achieving a Hospital Anxiety and Depression Scale-Anxiety (HADS-A) Score and Hospital Anxiety and Depression Scale-Depression (HADS-D) Score of < 8 at Week 16 |
|---|---|
| Description | The HADS is a 14-item questionnaire, with seven items related to anxiety (HADS-A) and seven items related to depression (HADS-D). Each item is scored from 0 to 3; scores for each subscale range from 0 to 21, with higher scores indicating more distress. For each domain, scores 7 or lower are considered normal, 8 to 10 are borderline, and 11 or higher indicate clinical anxiety or depression. |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study with HADS-A ≥ 8 or HADS-D ≥ 8 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 140 | 137 | 146 |
| Number (95% Confidence Interval) [percentage of participants] |
11.4
4.7%
|
46.0
18.9%
|
56.1
22.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 44.5 | |
| Confidence Interval |
(2-Sided) 95% 35.0 to 54.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 34.4 | |
| Confidence Interval |
(2-Sided) 95% 24.7 to 44.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Main Study: Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 16 |
|---|---|
| Description | The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. 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 are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. A score of 0 or 1 means that the disease has no effect at all. The DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit. |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for the main study who were ≥ 16 years old at Screening with DLQI score > 1 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Placebo | Upadacitinib 15 mg QD | Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Participants received placebo orally once a day for 16 weeks. | Participants received upadacitinib 15 mg orally once a day for 16 weeks. | Participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 257 | 252 | 256 |
| Number (95% Confidence Interval) [percentage of participants] |
4.7
1.9%
|
23.8
9.8%
|
37.9
15.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 30 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 33.3 | |
| Confidence Interval |
(2-Sided) 95% 26.9 to 39.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and secondary endpoints for upadacitinib 15 mg was strongly controlled using a graphical multiple testing procedure at the two-sided 0.05 level following a pre-specified α transfer path which includes downstream transfer along the endpoints sequence within each dose as well as cross-dose transfer. This endpoint was a multiplicity-controlled key secondary endpoint for EU/EMA regulatory purposes only. | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for strata (Baseline vIGA-AD categories and age [adolescent vs. adult]) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 19.1 | |
| Confidence Interval |
(2-Sided) 95% 13.3 to 24.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 16 |
|---|---|
| Description | 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. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population for adolescents (ITT_A) consists of all adolescent participants who were randomized in the main study or the adolescent sub-study. Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 60 | 58 | 62 |
| Number (95% Confidence Interval) [percentage of participants] |
13.3
5.5%
|
69.0
28.4%
|
73.4
29.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 59.9 | |
| Confidence Interval |
(2-Sided) 95% 45.9 to 73.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 55.8 | |
| Confidence Interval |
(2-Sided) 95% 41.1 to 70.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a vIGA-AD of 0 or 1 With a Reduction From Baseline of ≥ 2 Points at Week 16 |
|---|---|
| Description | The vIGA-AD is a validated assessment instrument to rate the severity of atopic dermatitis globally, based on the following scale: 0 - Clear: No signs of AD; 1 - Almost clear: Barely perceptible erythema, induration/papulation and/or lichenification, no oozing or crusting;; 2 - Mild: Slight but definite erythema, induration/papulation and/or minimal lichenification, no oozing or crusting; 3 - Moderate: Clearly perceptible erythema, induration/papulation and/or lichenification, possible oozing or crusting; 4 - Severe: Marked erythema, induration/papulation and/or lichenification; possible oozing or crusting. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 60 | 58 | 62 |
| Number (95% Confidence Interval) [percentage of participants] |
5.0
2.1%
|
44.8
18.4%
|
59.4
24%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 53.9 | |
| Confidence Interval |
(2-Sided) 95% 40.6 to 67.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 39.4 | |
| Confidence Interval |
(2-Sided) 95% 25.7 to 53.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 16 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 59 | 55 | 60 |
| Number (95% Confidence Interval) [percentage of participants] |
3.4
1.4%
|
38.2
15.7%
|
56.7
23%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 53.1 | |
| Confidence Interval |
(2-Sided) 95% 40.0 to 66.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 35.0 | |
| Confidence Interval |
(2-Sided) 95% 21.8 to 48.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving an EASI 90 Response at Week 16 |
|---|---|
| Description | 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. An EASI 90 response is defined as at least a 90% reduction (improvement) from Baseline in EASI score. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 60 | 58 | 62 |
| Number (95% Confidence Interval) [percentage of participants] |
1.7
0.7%
|
48.3
19.9%
|
62.0
25.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 60.2 | |
| Confidence Interval |
(2-Sided) 95% 47.5 to 72.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 46.7 | |
| Confidence Interval |
(2-Sided) 95% 33.4 to 59.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 4 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 59 | 55 | 60 |
| Number (95% Confidence Interval) [percentage of participants] |
3.4
1.4%
|
38.2
15.7%
|
50.0
20.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 46.4 | |
| Confidence Interval |
(2-Sided) 95% 33.2 to 59.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 34.9 | |
| Confidence Interval |
(2-Sided) 95% 21.4 to 48.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving an EASI 75 Response at Week 2 |
|---|---|
| Description | 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. An EASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in EASI score. |
| Time Frame | Baseline and Week 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 60 | 58 | 62 |
| Number (95% Confidence Interval) [percentage of participants] |
6.7
2.8%
|
37.9
15.6%
|
53.2
21.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 46.2 | |
| Confidence Interval |
(2-Sided) 95% 32.4 to 60.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 31.3 | |
| Confidence Interval |
(2-Sided) 95% 17.3 to 45.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 1 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst pruritus NRS was analyzed based on weekly rolling averages of daily scores. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with Worst Pruritus NRS (weekly average) ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 59 | 55 | 60 |
| Number (95% Confidence Interval) [percentage of participants] |
0.0
0%
|
12.7
5.2%
|
5.0
2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.075 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 5.0 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 10.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 12.7 | |
| Confidence Interval |
(2-Sided) 95% 3.9 to 21.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 2 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). |
| Time Frame | Baseline and Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 59 | 56 | 62 |
| Number (95% Confidence Interval) [percentage of participants] |
0.0
0%
|
8.9
3.7%
|
3.2
1.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.151 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 3.2 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 7.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Day 3 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). |
| Time Frame | Baseline and Day 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with Worst Pruritus NRS (daily score) ≥ 4 at Baseline; Non-responder imputation with no special data handling for missing data due to COVID-19 was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 59 | 56 | 62 |
| Number (95% Confidence Interval) [percentage of participants] |
1.7
0.7%
|
14.3
5.9%
|
9.7
3.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 12.9 | |
| Confidence Interval |
(2-Sided) 95% 3.4 to 22.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Experiencing a Flare During the Double-blind Treatment Period |
|---|---|
| Description | A flare, characterized as a clinically meaningful worsening in EASI, is defined as an increase in EASI score of ≥ 6.6 points from Baseline during the double-blind treatment period and prior to use of any rescue medication. Flares were assessed in participants with an EASI score of 65.4 or less at Baseline. |
| Time Frame | From first dose of study drug to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with an EASI score ≤ 65.4 at Baseline and at least one EASI post-baseline assessment prior to use of rescue medication. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 60 | 58 | 61 |
| Number (95% Confidence Interval) [percentage of participants] |
20.0
8.3%
|
1.7
0.7%
|
1.6
0.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | -18.0 | |
| Confidence Interval |
(2-Sided) 95% -28.0 to -8.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | -17.9 | |
| Confidence Interval |
(2-Sided) 95% -28.1 to -7.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 12 Points From Baseline in ADerm-IS Sleep Domain Score at Week 16 |
|---|---|
| Description | The ADerm-IS is a 10-item patient reported outcome questionnaire designed to assess a variety of impacts that participants experience from their AD. The ADerm-IS sleep domain consists of 3 questions designed to assess the impact of AD on sleep on a daily basis over a 24-hour recall period. The items include difficulty falling asleep, impact on sleep, and waking at night. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The ADerm-IS sleep domain score is the sum of the 3 item scores and ranges from 0 (no impact) to 30 (worst impact). The ADerm-IS sleep domain was analyzed based on weekly rolling averages of daily scores. The minimal clinically important difference for ADerm-IS sleep domain score is 12. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with ADerm-IS Sleep Domain score ≥ 12 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 42 | 40 | 44 |
| Number (95% Confidence Interval) [percentage of participants] |
9.5
3.9%
|
37.5
15.4%
|
61.4
24.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 51.5 | |
| Confidence Interval |
(2-Sided) 95% 34.8 to 68.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 29.2 | |
| Confidence Interval |
(2-Sided) 95% 11.8 to 46.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in ADerm-SS Skin Pain Score at Week 16 |
|---|---|
| Description | The ADerm-SS is an 11-item PRO questionnaire designed to assess signs and symptoms that patients may experience due to AD using a 24-hour recall period. For the skin pain item participants were asked to indicate on a daily basis how bad their worst skin pain due to AD was in the past 24 hours on an NRS from 0 (no pain) to 10 (worst imaginable pain). The minimal clinically important difference for ADerm-SS skin pain score is 4. The ADerm-SS skin pain score was analyzed based on weekly rolling averages of daily scores. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with ADerm-SS Skin Pain score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 53 | 48 | 51 |
| Number (95% Confidence Interval) [percentage of participants] |
7.5
3.1%
|
39.6
16.3%
|
60.8
24.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 53.2 | |
| Confidence Interval |
(2-Sided) 95% 38.4 to 68.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 31.8 | |
| Confidence Interval |
(2-Sided) 95% 16.5 to 47.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 28 Points From Baseline in ADerm-SS TSS-7 at Week 16 |
|---|---|
| Description | The ADerm-SS is an 11-item questionnaire designed to assess signs and symptoms that participants may experience due to AD using a 24-hour recall period. The 7-item total symptom score includes 7 symptoms (items 1-7 of the ADerm-SS), each assessed on a NRS from 0 (no symptom) to 10 (worst imaginable). The 7 symptoms included in the score are itch while asleep, itch while awake, skin pain (each assessed daily), skin cracking, skin cracking pain, dry skin, and skin flaking (assessed weekly). The TSS-7 score ranges from 0 to 70, with higher scores indicating worsening symptoms. The minimal clinically important difference for ADerm-SS TSS-7 is 28. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with ADerm-SS TSS-7 ≥ 28 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 55 | 48 | 55 |
| Number (95% Confidence Interval) [percentage of participants] |
10.9
4.5%
|
47.9
19.7%
|
60.0
24.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 48.9 | |
| Confidence Interval |
(2-Sided) 95% 33.8 to 64.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 37.3 | |
| Confidence Interval |
(2-Sided) 95% 21.1 to 53.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 11 Points From Baseline in ADerm-IS Emotional State Domain Score at Week 16 |
|---|---|
| Description | The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD. ADerm-IS emotional state sums three items [Items 8-10] measuring self-consciousness, embarrassment, and sadness with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The emotional state domain score ranges from 0 to 30, where higher scores represent worst impact. The minimal clinically important difference for ADerm-IS emotional state domain score is 11. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with ADerm-IS Emotional State Domain score ≥ 11 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 50 | 45 | 50 |
| Number (95% Confidence Interval) [percentage of participants] |
18.0
7.4%
|
60.0
24.7%
|
72.0
29.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 53.8 | |
| Confidence Interval |
(2-Sided) 95% 37.4 to 70.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 42.0 | |
| Confidence Interval |
(2-Sided) 95% 24.3 to 59.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 14 Points From Baseline in ADerm-IS Daily Activities Domain Score at Week 16 |
|---|---|
| Description | The ADerm-IS is a 10-item PRO questionnaire designed to assess a variety of impacts that participants experience from their AD. ADerm-IS daily activities sums four items measuring limitations of household, physical, and social activities, and difficulty concentrating with a 7-day recall. Each question is scored on an 11-point NRS from 0 (no impact) to 10 (extreme impact). The daily activities domain score ranges from 0 to 40, where higher scores represent worst impact. The minimal clinically important difference for the ADerm-IS daily activities domain score is 14. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with ADerm-IS Daily Activities Domain Score ≥ 14 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 49 | 40 | 50 |
| Number (95% Confidence Interval) [percentage of participants] |
22.4
9.3%
|
52.5
21.6%
|
68.0
27.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 45.3 | |
| Confidence Interval |
(2-Sided) 95% 28.0 to 62.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 29.8 | |
| Confidence Interval |
(2-Sided) 95% 10.7 to 48.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving an EASI 100 Response at Week 16 |
|---|---|
| Description | 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. An EASI 100 response is defined as a 100% reduction (improvement) from Baseline in EASI score. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population for adolescents; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 60 | 58 | 62 |
| Number (95% Confidence Interval) [percentage of participants] |
1.7
0.7%
|
15.5
6.4%
|
19.4
7.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 17.1 | |
| Confidence Interval |
(2-Sided) 95% 7.5 to 26.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.006 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 13.7 | |
| Confidence Interval |
(2-Sided) 95% 3.9 to 23.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percent Change From Baseline in Worst Pruritus NRS at Week 16 |
|---|---|
| Description | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Worst Pruritus NRS was analyzed based on weekly rolling averages of daily scores. A negative change from Baseline indicates improvement. |
| Time Frame | Baseline (last available rolling average before the first dose of study drug) and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements including observed measurements at all visits, except that measurements after any rescue medication were excluded. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 27 | 49 | 55 |
| Least Squares Mean (95% Confidence Interval) [percent change] |
-11.02
|
-47.56
|
-66.95
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, and Baseline vIGA-AD category in the model. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -55.93 | |
| Confidence Interval |
(2-Sided) 95% -70.32 to -41.55 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.284 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, and Baseline vIGA-AD category in the model. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -36.54 | |
| Confidence Interval |
(2-Sided) 95% -51.12 to -21.96 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.384 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percent Change From Baseline in EASI Score at Week 16 |
|---|---|
| Description | 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 Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements including observed measurements at all visits, except that measurements after any rescue medication were excluded. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 31 | 53 | 52 |
| Least Squares Mean (95% Confidence Interval) [percent change] |
-42.19
|
-77.85
|
-84.81
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-Effect Model Repeat Measurement with Baseline, treatment, visit, treatment by visit interaction, and Baseline vIGA-AD category in the model. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -42.62 | |
| Confidence Interval |
(2-Sided) 95% -55.34 to -29.90 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.432 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-Effect Model Repeat Measurement with Baseline, treatment, visit, treatment by visit interaction, and Baseline vIGA-AD category in the model. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -35.66 | |
| Confidence Interval |
(2-Sided) 95% -48.41 to -22.90 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.447 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in POEM Total Score at Week 16 |
|---|---|
| Description | The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults. Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema). A change in POEM score of 3.4 points is considered the minimal clinically important difference. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with POEM score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 57 | 56 | 57 |
| Number (95% Confidence Interval) [percentage of participants] |
28.1
11.6%
|
66.1
27.2%
|
80.7
32.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 52.5 | |
| Confidence Interval |
(2-Sided) 95% 36.9 to 68.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 38.1 | |
| Confidence Interval |
(2-Sided) 95% 21.2 to 54.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in DLQI Score at Week 16 |
|---|---|
| Description | The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. 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 are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. the DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents who were ≥ 16 years old at Screening with DLQI score ≥ 4 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 26 | 22 | 30 |
| Number (95% Confidence Interval) [percentage of participants] |
19.2
7.9%
|
68.2
28.1%
|
73.3
29.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 55.9 | |
| Confidence Interval |
(2-Sided) 95% 35.5 to 76.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 49.6 | |
| Confidence Interval |
(2-Sided) 95% 26.3 to 72.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percent Change From Baseline in SCORAD Score at Week 16 |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with non-missing Baseline and Week 16 values; missing data were handled using a mixed-effect model with repeated measurements including observed measurements at all visits, except that measurements after any rescue medication were excluded. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 30 | 54 | 49 |
| Least Squares Mean (95% Confidence Interval) [percent change] |
-27.91
|
-57.89
|
-72.81
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, and Baseline vIGA-AD category | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -44.90 | |
| Confidence Interval |
(2-Sided) 95% -57.74 to -32.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.492 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | Mixed-effect model repeat measurement with Baseline, treatment, visit, treatment by visit interaction, and Baseline vIGA-AD category | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -29.98 | |
| Confidence Interval |
(2-Sided) 95% -42.60 to -17.36 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.383 |
|
| Estimation Comments | Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving HADS-A Score and HADS-D Score of < 8 at Week 16 |
|---|---|
| Description | The HADS is a 14-item questionnaire, with seven items related to anxiety (HADS-A) and seven items related to depression (HADS-D). Each item is scored from 0 to 3; scores for each subscale range from 0 to 21, with higher scores indicating more distress. For each domain, scores 7 or lower are considered normal, 8 to 10 are borderline, and 11 or higher indicate clinical anxiety or depression. |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents with HADS-A ≥ 8 or HADS-D ≥ 8 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 25 | 24 | 32 |
| Number (95% Confidence Interval) [percentage of participants] |
16.0
6.6%
|
37.5
15.4%
|
43.8
17.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.016 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 27.8 | |
| Confidence Interval |
(2-Sided) 95% 5.2 to 50.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.062 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 22.3 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 45.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Adolescents: Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 16 |
|---|---|
| Description | The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. 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 are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. A score of 0 or 1 means that the disease has no effect at all. the DLQI was administered to participants who were ≥ 16 (16 to 75) years old at the time of the Screening visit. |
| Time Frame | Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat population for adolescents who were ≥ 16 years old at Screening with DLQI score > 1 at Baseline; Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 (NRI-C) was used. |
| Arm/Group Title | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD |
|---|---|---|---|
| Arm/Group Description | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. |
| Measure Participants | 26 | 22 | 32 |
| Number (95% Confidence Interval) [percentage of participants] |
7.7
3.2%
|
13.6
5.6%
|
46.9
19%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 38.9 | |
| Confidence Interval |
(2-Sided) 95% 18.4 to 59.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.510 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusted for stratum (Baseline vIGA-AD categories) | |
| Method of Estimation | Estimation Parameter | Adjusted Response Rate Difference |
| Estimated Value | 5.9 | |
| Confidence Interval |
(2-Sided) 95% -11.7 to 23.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Adverse Events
| Time Frame | From first dose of study drug up to Week 16, or 30 days after last dose for participants who did not enter the blinded extension period. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| Arm/Group Title | Adults: Placebo | Adults: Upadacitinib 15 mg QD | Adults: Upadacitinib 30 mg QD | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD | ||||||
| Arm/Group Description | Participants ≥ 18 years old received placebo orally once a day for 16 weeks. | Participants ≥ 18 years old received upadacitinib 15 mg orally once a day for 16 weeks. | Participants ≥ 18 years old received upadacitinib 30 mg orally once a day for 16 weeks. | Adolescent participants received placebo orally once a day for 16 weeks. | Adolescent participants received upadacitinib 15 mg orally once a day for 16 weeks. | Adolescent participants received upadacitinib 30 mg orally once a day for 16 weeks. | ||||||
All Cause Mortality |
||||||||||||
| Adults: Placebo | Adults: Upadacitinib 15 mg QD | Adults: Upadacitinib 30 mg QD | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/242 (0%) | 0/243 (0%) | 0/247 (0%) | 0/60 (0%) | 0/58 (0%) | 0/62 (0%) | ||||||
Serious Adverse Events |
||||||||||||
| Adults: Placebo | Adults: Upadacitinib 15 mg QD | Adults: Upadacitinib 30 mg QD | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/242 (2.5%) | 3/243 (1.2%) | 7/247 (2.8%) | 3/60 (5%) | 2/58 (3.4%) | 0/62 (0%) | ||||||
| Eye disorders | ||||||||||||
| RETINAL DETACHMENT | 0/242 (0%) | 0 | 1/243 (0.4%) | 1 | 0/247 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| RETINAL TEAR | 0/242 (0%) | 0 | 1/243 (0.4%) | 1 | 0/247 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| General disorders | ||||||||||||
| INFLUENZA LIKE ILLNESS | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 1/247 (0.4%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| Infections and infestations | ||||||||||||
| CELLULITIS | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 0/247 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| ECZEMA HERPETICUM | 0/242 (0%) | 0 | 1/243 (0.4%) | 1 | 0/247 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| IMPETIGO | 1/242 (0.4%) | 1 | 0/243 (0%) | 0 | 0/247 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| ORCHITIS | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 1/247 (0.4%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| PNEUMONIA | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 1/247 (0.4%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| SUBCUTANEOUS ABSCESS | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 0/247 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||
| FALL | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 1/247 (0.4%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| HEAT STROKE | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 1/247 (0.4%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| ARTHRALGIA | 1/242 (0.4%) | 1 | 0/243 (0%) | 0 | 0/247 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| RHABDOMYOLYSIS | 0/242 (0%) | 0 | 1/243 (0.4%) | 1 | 0/247 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| ANAL SQUAMOUS CELL CARCINOMA | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 1/247 (0.4%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| MIGRAINE | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 0/247 (0%) | 0 | 1/60 (1.7%) | 1 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| Psychiatric disorders | ||||||||||||
| BIPOLAR DISORDER | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 1/247 (0.4%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| SUICIDE ATTEMPT | 1/242 (0.4%) | 1 | 0/243 (0%) | 0 | 1/247 (0.4%) | 1 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/62 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| PNEUMOMEDIASTINUM | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 0/247 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 | 0/62 (0%) | 0 |
| PULMONARY EMBOLISM | 1/242 (0.4%) | 1 | 0/243 (0%) | 0 | 0/247 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| DERMATITIS ATOPIC | 2/242 (0.8%) | 2 | 0/243 (0%) | 0 | 0/247 (0%) | 0 | 1/60 (1.7%) | 1 | 1/58 (1.7%) | 1 | 0/62 (0%) | 0 |
| ECZEMA | 1/242 (0.4%) | 1 | 0/243 (0%) | 0 | 0/247 (0%) | 0 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
| Vascular disorders | ||||||||||||
| HYPERTENSIVE EMERGENCY | 0/242 (0%) | 0 | 0/243 (0%) | 0 | 1/247 (0.4%) | 1 | 0/60 (0%) | 0 | 0/58 (0%) | 0 | 0/62 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| Adults: Placebo | Adults: Upadacitinib 15 mg QD | Adults: Upadacitinib 30 mg QD | Adolescents: Placebo | Adolescents: Upadacitinib 15 mg QD | Adolescents: Upadacitinib 30 mg QD | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 52/242 (21.5%) | 78/243 (32.1%) | 94/247 (38.1%) | 15/60 (25%) | 21/58 (36.2%) | 25/62 (40.3%) | ||||||
| General disorders | ||||||||||||
| FATIGUE | 2/242 (0.8%) | 2 | 2/243 (0.8%) | 2 | 8/247 (3.2%) | 9 | 0/60 (0%) | 0 | 3/58 (5.2%) | 3 | 0/62 (0%) | 0 |
| Infections and infestations | ||||||||||||
| NASOPHARYNGITIS | 11/242 (4.5%) | 20 | 14/243 (5.8%) | 17 | 18/247 (7.3%) | 18 | 2/60 (3.3%) | 2 | 2/58 (3.4%) | 2 | 0/62 (0%) | 0 |
| UPPER RESPIRATORY TRACT INFECTION | 11/242 (4.5%) | 13 | 13/243 (5.3%) | 14 | 14/247 (5.7%) | 19 | 1/60 (1.7%) | 1 | 6/58 (10.3%) | 6 | 3/62 (4.8%) | 3 |
| Investigations | ||||||||||||
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 4/242 (1.7%) | 5 | 8/243 (3.3%) | 8 | 10/247 (4%) | 10 | 1/60 (1.7%) | 1 | 3/58 (5.2%) | 3 | 6/62 (9.7%) | 6 |
| Nervous system disorders | ||||||||||||
| HEADACHE | 10/242 (4.1%) | 11 | 17/243 (7%) | 20 | 16/247 (6.5%) | 17 | 2/60 (3.3%) | 4 | 3/58 (5.2%) | 4 | 5/62 (8.1%) | 6 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| ASTHMA | 0/242 (0%) | 0 | 1/243 (0.4%) | 1 | 2/247 (0.8%) | 2 | 0/60 (0%) | 0 | 3/58 (5.2%) | 5 | 2/62 (3.2%) | 3 |
| OROPHARYNGEAL PAIN | 4/242 (1.7%) | 4 | 4/243 (1.6%) | 4 | 4/247 (1.6%) | 5 | 0/60 (0%) | 0 | 4/58 (6.9%) | 4 | 2/62 (3.2%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| ACNE | 5/242 (2.1%) | 5 | 31/243 (12.8%) | 32 | 38/247 (15.4%) | 39 | 2/60 (3.3%) | 2 | 6/58 (10.3%) | 6 | 9/62 (14.5%) | 10 |
| DERMATITIS ATOPIC | 17/242 (7%) | 19 | 7/243 (2.9%) | 7 | 2/247 (0.8%) | 2 | 8/60 (13.3%) | 8 | 1/58 (1.7%) | 1 | 1/62 (1.6%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
| Name/Title | Global Medical Services |
|---|---|
| Organization | AbbVie |
| Phone | 800-633-9110 |
| abbvieclinicaltrials@abbvie.com |
Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT03607422
Other Study ID Numbers:
- M18-891
- 2018-001383-28
First Posted:
Jul 31, 2018
Last Update Posted:
Mar 28, 2022
Last Verified:
Mar 1, 2022