TRuE AD2 - An Efficacy and Safety Study of Ruxolitinib Cream in Adolescents and Adults With Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of ruxolitinib cream in adolescents and adults with atopic dermatitis (AD).

Official Title
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Topical Ruxolitinib Evaluation in Atopic Dermatitis Study 2 (TRuE AD2) - A Phase 3, Double-Blind, Randomized, 8-Week, Vehicle-Controlled Efficacy and Safety Study of Ruxolitinib Cream Followed by a Long-Term Safety Extension Period in Adolescents and Adults With Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Ruxolitinib cream
* Drug: Vehicle cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adolescents aged ≥ 12 to 17 years, inclusive, and men and women aged ≥ 18 years. Participants diagnosed with atopic dermatitis (AD) as defined by the Hanifin and Rajka criteria. AD duration of at least 2 years. Participants with an Investigator's Global Assessment (IGA) score of 2 to 3 at Screening and Baseline (VC Period) and 0 to 4 at Week 8 (LTS Period). Participants with percentage body surface area (%BSA) (excluding scalp) of AD involvement of 3% to 20% at Screening and Baseline (VC Period) and 0% to 20% at Week 8 (LTS Period). Participants who agree to discontinue all agents used to treat AD from Screening through the final follow-up visit. Participants who have at least 1 target lesion that measures approximately 10 cm^2 or more at Screening and Baseline. Lesion must be representative of the participant's disease state and not be located on the hands, feet, or genitalia. Willingness to avoid pregnancy or fathering of children. Exclusion Criteria: Unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator in the 4 weeks prior to Baseline. Concurrent conditions and history of other diseases: Immunocompromised. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before Baseline. Active acute bacterial, fungal, or viral skin infection within 1 week before Baseline. Any other concomitant skin disorder, pigmentation, or extensive scarring that, in the opinion of the investigator, may interfere with the evaluation of AD lesions or compromise participant safety. Presence of AD lesions only on the hands or feet without prior history of involvement of other classical areas of involvement such as the face or the folds. Other types of eczema. Any serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. Use of any of the following treatments within the indicated washout period before Baseline: 5 half-lives or 12 weeks, whichever is longer - biologic agents (e.g. dupilumab). 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (e.g. mycophenolate or tacrolimus). 2 weeks - immunizations and sedating antihistamines, unless on long-term stable regimen (nonsedating antihistamines are permitted). 1 week - use of other topical treatments for AD (other than bland emollients). Diluted sodium hypochlorite bleach baths are allowed as long as they do not exceed 2 baths per week and their frequency remains the same throughout the study. Participants who have previously received Janus kinase (JAK) inhibitors, systemic or topical. Ultraviolet (UV) light therapy or prolonged exposure to natural or artificial sources of UV radiation within 2 weeks prior to Baseline and/or intention to have such exposure during the study, which is thought by the investigator to potentially impact the participant's AD. Positive serology test results at screening for human immunodeficiency virus (HIV) antibody. Liver function tests: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2 × upper limit of normal (ULN); alkaline phosphatase and/or bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%). Pregnant or lactating participants, or those considering pregnancy. History of alcoholism or drug addiction within 1 year before screening or current alcohol or drug use that, in the opinion of the investigator, will interfere with the participant's ability to comply with the administration schedule and study assessments. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before Baseline with another investigational medication or current enrollment in another investigational drug protocol.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vehicle Control (VC) Period: Vehicle Cream BID<br>Participants received ruxolitinib matching vehicle cream, applied topically to the affected areas as a thin film twice daily (BID) 8 hours apart from Day 1 up to Week 8. Participants applied cream BID to areas identified at Baseline even if the areas improved. | Drug: Vehicle cream<br>* Ruxolitinib matching vehicle cream.<br>|
| Experimental: VC Period: Ruxolitinib 0.75% Cream BID<br>Participants received ruxolitinib 0.75% cream, applied topically to the affected areas as a thin film BID 8 hours apart from Day 1 up to Week 8. Participants applied cream BID to areas identified at Baseline even if the areas improved. | Drug: Ruxolitinib cream<br>* Ruxolitinib 0.75% or 1.5% cream.<br>* Other names: INCB018424 phosphate cream;|
| Experimental: VC Period: Ruxolitinib 1.5% Cream BID<br>Participants received ruxolitinib 1.5% cream, applied topically to the affected areas as a thin film BID 8 hours apart from Day 1 up to Week 8. Participants applied cream BID to areas identified at Baseline even if the areas improved. | Drug: Ruxolitinib cream<br>* Ruxolitinib 0.75% or 1.5% cream.<br>* Other names: INCB018424 phosphate cream;|
| Experimental: Long-Term Safety (LTS) Period: Vehicle Cream to Ruxolitinib 0.75% Cream BID<br>Participants who applied vehicle cream during the VC Period were randomized at Week 8 to apply ruxolitinib 0.75% cream, topically to the affected areas as a thin film BID as needed from Week 8 up to Week 52. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence. | Drug: Ruxolitinib cream<br>* Ruxolitinib 0.75% or 1.5% cream.<br>* Other names: INCB018424 phosphate cream;|
| Experimental: LTS Period: Vehicle Cream to Ruxolitinib 1.5% Cream BID<br>Participants who applied vehicle cream during the VC Period were randomized at Week 8 to apply ruxolitinib 1.5% cream, topically to the affected areas as a thin film BID as needed from Week 8 up to Week 52. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence. | Drug: Ruxolitinib cream<br>* Ruxolitinib 0.75% or 1.5% cream.<br>* Other names: INCB018424 phosphate cream;|
| Experimental: LTS Period: Ruxolitinib 0.75% Cream BID<br>Participants who applied ruxolitinib 0.75% cream during the VC Period, continued applying ruxolitinib 0.75% cream, topically to the affected areas as a thin film BID as needed from Week 8 up to Week 52. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence. | Drug: Ruxolitinib cream<br>* Ruxolitinib 0.75% or 1.5% cream.<br>* Other names: INCB018424 phosphate cream;|
| Experimental: LTS Period: Ruxolitinib 1.5% Cream BID<br>Participants who applied ruxolitinib 1.5% cream during the VC Period, continued applying ruxolitinib 1.5% cream, topically to the affected areas as a thin film BID as needed from Week 8 up to Week 52. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence. | Drug: Ruxolitinib cream<br>* Ruxolitinib 0.75% or 1.5% cream.<br>* Other names: INCB018424 phosphate cream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VC Period: Percentage of Participants Who Achieved Investigator's Global Assessment - Treatment Success (IGA-TS) at Week 8 | The IGA is an overall eczema severity rating on a 5-point scale ranging from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, induration/papulation, and oozing/crusting. The IGA-TS is defined as an IGA score of 0 (clear skin) or 1 (almost clear skin) with ≥ 2 grade improvement from Baseline. | Baseline to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VC Period: Percentage of Participants Who Achieved Eczema Area and Severity Index 75 (EASI75) at Week 8 | EASI scoring system examines 4 areas of the body (head/neck, trunk, upper limbs, and lower limbs) and weights them for participants of at least 8 years of age. Each of the 4 body regions is assessed separately for erythema (E), induration/papulation/edema (I), excoriations (Ex), and lichenification (l) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 and the severity strata are as follows: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. An EASI75 responder was defined as a participant achieving 75% or greater improvement from Baseline in EASI score. | Baseline to Week 8 | 
| VC Period: Percentage of Participants With a ≥ 4-Point Improvement in Itch Numerical Rating Scale (NRS) Score From Baseline to Week 8 | The Itch NRS is a daily participant-reported measure (24-hour recall), of the worst level of itch intensity using a diary. Participants are asked to rate the itching severity because of their AD by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best describes their worst level of itching in the past 24 hours. | Baseline to Week 8 | 
| VC Period: Percentage of Participants With a Clinically Meaningful (≥ 6-Point) Improvement in the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form - Sleep Disturbance (8b - 24-Hour Recall) Score at Week 8 | The PROMIS Short Form - Sleep Disturbance (8b) questionnaire assesses participant's self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. This questionnaire is completed in the morning by the participant where each item asks the participant to rate the severity of the participant's sleep disturbance. It is a 5-point scale with a range in score from 8 to 40, with higher scores indicating greater severity of sleep disturbance. | Baseline to Week 8 | 
| VC Period: Percentage of Participants With a Clinically Meaningful (≥ 6-Point) Improvement in the PROMIS Short Form - Sleep-Related Impairment (8a - 24-Hour Recall) Score at Week 8 | The PROMIS Short Form - Sleep-Related Impairment (8a) questionnaire assesses participant's self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours and the perceived functional impairments during wakefulness associated with sleep problems or impaired alertness. The questionnaire is filled in the evening where each item asks the participant to rate the severity of the participant's sleep impairment. It has 8 simple questions with a 5-point scale with a range in score from 8 to 40, with higher scores indicating greater severity of sleep-related impairment. Each item asks the participant to rate the severity of the participant's sleep impairment. | Baseline to Week 8 | 
| VC Period: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (SAE) | An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or an important medical event may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above. A TEAE or treatment emergent SAE is any AE or SAE either reported for first time or worsening of a pre-existing event after first dose of study drug. | From date of randomization up to Week 8 | 
| LTS Period: Percentage of Participants With at Least One TEAE and Treatment Emergent SAE | An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or an important medical event may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above. A TEAE or treatment emergent SAE is any AE or SAE either reported for first time or worsening of a pre-existing event after first dose of study drug. | From first dose date in LTS Period (Week 8) until last follow-up visit (up to 52 weeks) | 
| VC Period: Percentage of Participants Who Achieved an IGA-TS at Weeks 2 and 4 | The IGA is an overall eczema severity rating on a 5-point scale ranging from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, induration/papulation, and oozing/crusting. The IGA-TS is defined as an IGA score of 0 (clear skin) or 1 (almost clear skin) with ≥ 2 grade improvement from Baseline. | Baseline to Weeks 2 and 4 | 
| VC Period: Percentage of Participants Achieving an IGA of 0 or 1 | The IGA is an overall eczema severity rating on a 5-point scale ranging from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, induration/papulation, and oozing/crusting. | Weeks 2, 4 and 8 | 
| LTS Period: Percentage of Participants Achieving an IGA of 0 or 1 | The IGA is an overall eczema severity rating on a 5-point scale ranging from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, induration/papulation, and oozing/crusting. | Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| VC Period: Percentage of Participants With a ≥ 4-Point Improvement in Itch NRS Score From Baseline to Weeks 2 and 4 | The Itch NRS is a daily participant-reported measure (24-hour recall), of the worst level of itch intensity using a diary. Participants are asked to rate the itching severity because of their AD by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best describes their worst level of itching in the past 24 hours. | Baseline to Weeks 2 and 4 | 
| VC Period: Percentage of Participants Who Achieved EASI50 | EASI scoring system examines 4 areas of the body (head/neck, trunk, upper limbs, and lower limbs) and weights them for participants of at least 8 years of age. Each of the 4 body regions is assessed separately for erythema (E), induration/papulation/edema (I), excoriations (Ex), and lichenification (l) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 and the severity strata are as follows: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. An EASI50 responder was defined as a participant achieving 50% or greater improvement from Baseline in EASI score. | Baseline to Weeks 2, 4 and 8 | 
| VC Period: Percentage of Participants Who Achieved EASI75 at Weeks 2 and 4 | EASI scoring system examines 4 areas of the body (head/neck, trunk, upper limbs, and lower limbs) and weights them for participants of at least 8 years of age. Each of the 4 body regions is assessed separately for erythema (E), induration/papulation/edema (I), excoriations (Ex), and lichenification (l) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 and the severity strata are as follows: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. An EASI75 responder was defined as a participant achieving 75% or greater improvement from Baseline in EASI score. | Baseline to Weeks 2 and 4 | 
| VC Period: Percentage of Participants Who Achieved EASI90 | EASI scoring system examines 4 areas of the body (head/neck, trunk, upper limbs, and lower limbs) and weights them for participants of at least 8 years of age. Each of the 4 body regions is assessed separately for erythema (E), induration/papulation/edema (I), excoriations (Ex), and lichenification (l) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 and the severity strata are as follows: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. An EASI90 responder was defined as a participant achieving 90% or greater improvement from Baseline in EASI score. | Baseline to Weeks 2, 4 and 8 | 
| VC Period: Percent Change From Baseline in EASI Score | EASI scoring system examines 4 areas of the body (head/neck, trunk, upper limbs, and lower limbs) and weights them for participants of at least 8 years of age. Each of the 4 body regions is assessed separately for erythema (E), induration/papulation/edema (I), excoriations (Ex), and lichenification (l) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe). Half scores are allowed between severities 1, 2 and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 and the severity strata are as follows: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. A negative change from Baseline indicates improvement. | Baseline, Weeks 2, 4 and 8 | 
| VC Period: Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score | The SCORAD is a tool to assess extent and severity of eczema. To determine the extent, the rule of nines or handprint method is used to assess eczema affected area (A). To determine disease severity (B) it evaluates 6 clinical characteristics: 1. redness, 2. swelling, 3. oozing/crusting, 4. scratch marks, 5. lichenification, and 6. dryness on a 4-point scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), added to give B with maximum score of 18. Subjective symptoms (C) of itch and sleeplessness are assessed using a visual analogue scale where 0 is no itch (or no sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), added to give C with maximum score of 20. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combined using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. A negative change from Baseline indicates improvement. | Baseline, Weeks 2, 4 and 8 | 
| VC Period: Change From Baseline in Itch NRS Score | The Itch NRS is a daily participant-reported measure (24-hour recall), of the worst level of itch intensity using a diary. Participants are asked to rate the itching severity because of their AD by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best describes their worst level of itching in the past 24 hours. A negative change from Baseline indicates improvement. | Baseline, Weeks 2, 4 and 8 | 
| VC Period: Time to Achieve Itch NRS Score Improvement of at Least 2, 3, or 4 Points | The Itch NRS is a daily participant-reported measure (24-hour recall), of the worst level of itch intensity using a diary. Participants are asked to rate the itching severity because of their AD by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best describes their worst level of itching in the past 24 hours. Kaplan-Meier estimation method was used for analyses. | Up to Week 8 | 
| VC Period: Change From Baseline in Skin Pain NRS Score | The Skin Pain NRS is a daily patient-reported measure (24-hour recall), of the worst level of pain intensity from 0 (no pain) to 10 (worst imaginable pain) using a diary. Participants will be asked, Rate the pain severity from your atopic dermatitis skin changes by selecting a number that best describes your worst level of pain in the past 24 hours. A negative change from Baseline indicates improvement. | Baseline, Weeks 2, 4 and 8 | 
| VC Period: Percentage of Participants With a Clinically Meaningful (≥ 6-Point) Improvement in the PROMIS Short Form - Sleep Disturbance (8b) 24-Hour Recall Score at Weeks 2 and 4 | The PROMIS Short Form - Sleep Disturbance (8b) questionnaire assesses participant's self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. This questionnaire is completed in the morning by the participant where each item asks the participant to rate the severity of the participant's sleep disturbance. It is a 5-point scale with a range in score from 8 to 40, with higher scores indicating greater severity of sleep disturbance. | Weeks 2 and 4 | 
| VC Period: Percentage of Participants With a Clinically Meaningful (≥ 6-Point) Improvement in the PROMIS Short Form - Sleep-Related Impairment (8a) 24-Hour Recall Score at Weeks 2 and 4 | The PROMIS Short Form - Sleep-Related Impairment (8a) questionnaire assesses participant's self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours and the perceived functional impairments during wakefulness associated with sleep problems or impaired alertness. The questionnaire is filled in the evening where each item asks the participant to rate the severity of the participant's sleep impairment. It has 8 simple questions with a 5-point scale with a range in score from 8 to 40, with higher scores indicating greater severity of sleep-related impairment. | Weeks 2 and 4 | 
| VC Period: Change From Baseline in PROMIS Short Form - Sleep Disturbance (8b) 24-Hour Recall Score | The PROMIS Short Form - Sleep Disturbance (8b) questionnaire assesses participant's self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. This questionnaire is completed in the morning by the participant where each item asks the participant to rate the severity of the participant's sleep disturbance. It is a 5-point scale with a range in score from 8 to 40, with higher scores indicating greater severity of sleep disturbance. A negative change from Baseline indicates improvement. | Baseline, Weeks 2, 4 and 8 | 
| VC Period: Change From Baseline in PROMIS Short Form - Sleep-Related Impairment (8a) 24-Hour Recall Score | The PROMIS Short Form - Sleep-Related Impairment (8a) questionnaire assesses participant's self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours and the perceived functional impairments during wakefulness associated with sleep problems or impaired alertness. The questionnaire is filled in the evening where each item asks the participant to rate the severity of the participant's sleep impairment. It has 8 simple questions with a 5-point scale with a range in score from 8 to 40, with higher scores indicating greater severity of sleep-related impairment. A negative change from Baseline indicates improvement. | Baseline, Weeks 2, 4 and 8 | 
| LTS Period: Change From Baseline in PROMIS Short Form - Sleep-Related Impairment (8a) 7-Day Recall Score | The PROMIS Short Form - Sleep-Related Impairment (8a) questionnaire assesses participant's self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours and the perceived functional impairments during wakefulness associated with sleep problems or impaired alertness. The questionnaire is filled in the evening where each item asks the participant to rate the severity of the participant's sleep impairment. It has 8 simple questions with a 5-point scale with a range in score from 8 to 40, with higher scores indicating greater severity of sleep-related impairment. A negative change from Baseline indicates improvement. | Baseline, Weeks 12, 24, and 52 | 
| LTS Period: Change From Baseline in PROMIS Short Form - Sleep Disturbance (8b) 7-Day Recall Score | The PROMIS Short Form - Sleep Disturbance (8b) questionnaire assesses participant's self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. This questionnaire is completed in the morning by the participant where each item asks the participant to rate the severity of the participant's sleep disturbance. It is a 5-point scale with a range in score from 8 to 40, with higher scores indicating greater severity of sleep disturbance. A negative change from Baseline indicates improvement. | Baseline, Weeks 12, 24, and 52 | 
| VC Period: Change From Baseline in Atopic Dermatitis Afflicted Percentage of Body Surface Area (%BSA) | Body surface area affected by AD was assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region was assessed for disease extent ranging from 0% to 100% involvement. The overall total percentage was reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1*BSA head and neck + 0.3*BSA trunk + 0.2* BSA upper limbs + 0.4*BSA lower limbs. A negative change from Baseline indicates improvement. | Baseline, Weeks 2, 4 and 8 | 
| LTS Period: Change From Baseline in Atopic Dermatitis Afflicted %BSA | Body surface area affected by AD was assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region was assessed for disease extent ranging from 0% to 100% involvement. The overall total percentage was reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1*BSA head and neck + 0.3*BSA trunk + 0.2* BSA upper limbs + 0.4*BSA lower limbs. A negative change from Baseline indicates improvement. | Baseline, Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 
| VC Period: Change From Baseline in Patient-Oriented Eczema Measure (POEM) Score | The POEM is a 7-question quality-of-life assessment that asks how many days the participant has been bothered by various aspects of their skin condition during the past 7 days. It assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life. A negative change from Baseline indicates improvement. | Baseline, Weeks 2, 4 and 8 | 
| LTS Period: Change From Baseline in POEM Score | The POEM is a 7-question quality-of-life assessment that asks how many days the participant has been bothered by various aspects of their skin condition during the past 7 days. It assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life. A negative change from Baseline indicates improvement. | Baseline, Weeks 12, 24 and 52 | 
| VC Period: Change From Baseline in Dermatology Life Quality Index (DLQI) Score | The DLQI is a simple, 10 question (Q) validated quality-of-life questionnaire to measure how much the skin problem has affected the participant. It covers 6 domains including symptoms and feelings (Q1 and Q2), daily activities (Q3 and Q4), leisure (Q5 and Q6), work and school (Q7), personal relationships (Q8 and Q9), and treatment(Q10). The recall Period of this scale is over the last week. Response categories include 0-not at all, 1-a little, 2-a lot, and 3-very much, and unanswered or not relevant responses scored as 0. Scores range from 0 (no impact on participant's life) to 30 (extremely large effect on participant's life), and a 4-point change from Baseline is considered as the minimal clinically important difference threshold. A negative change from Baseline indicates less impact of the skin problem on participant's life. | Baseline, Weeks 2, 4, and 8 | 
| LTS Period: Change From Baseline in DLQI Score | The DLQI is a simple, 10 question (Q) validated quality-of-life questionnaire to measure how much the skin problem has affected the participant. It covers 6 domains including symptoms and feelings (Q1 and Q2), daily activities (Q3 and Q4), leisure (Q5 and Q6), work and school (Q7), personal relationships (Q8 and Q9), and treatment(Q10). The recall Period of this scale is over the last week. Response categories include 0-not at all, 1-a little, 2-a lot, and 3-very much, and unanswered or not relevant responses scored as 0. Scores range from 0 (no impact on participant's life) to 30 (extremely large effect on participant's life), and a 4-point change from Baseline is considered as the minimal clinically important difference threshold. A negative change from Baseline indicates less impact of the skin problem on participant's life. | Baseline, Weeks 12, 24, and 52 | 
| VC Period: Change From Baseline in Children Dermatology Life Quality Index (CDLQI) Score | CDLQI is the youth/children's version of the DLQI. The CDLQI is a simple 10 question (Q) validated quality-of-life questionnaire. It covers 6 domains including symptoms and feelings (Q1 and Q2), leisure (Q4, Q5, and Q6), school or holidays (Q7), personal relationships (Q3 and Q8), sleep (Q9) and treatment (Q10). Response categories include 0-not at all, 1-a little, 2-a lot, and 3-very much, and unanswered or not relevant responses scored as 0. The total DLQI score is calculated by adding the score of each question resulting in a maximum score of 30 (extremely large effect on participant's life) and a minimum score of 0 (no impact on participant's life) and a 4-point change from Baseline is considered as the minimal clinically important difference threshold. A negative change from Baseline indicates less impact of the skin problem on participant's life. | Baseline, Weeks 2, 4, and 8 | 
| LTS Period: Change From Baseline in CDLQI Score | CDLQI is the youth/children's version of the DLQI. The CDLQI is a simple 10 question (Q) validated quality-of-life questionnaire. It covers 6 domains including symptoms and feelings (Q1 and Q2), leisure (Q4, Q5, and Q6), school or holidays (Q7), personal relationships (Q3 and Q8), sleep (Q9) and treatment (Q10). Response categories include 0-not at all, 1-a little, 2-a lot, and 3-very much, and unanswered or not relevant responses scored as 0. The total DLQI score is calculated by adding the score of each question resulting in a maximum score of 30 (extremely large effect on participant's life) and a minimum score of 0 (no impact on participant's life) and a 4-point change from Baseline is considered as the minimal clinically important difference threshold. A negative change from Baseline indicates less impact of the skin problem on participant's life. | Baseline, Weeks 12, 24, and 52 | 
| VC Period: Mean Patient Global Impression of Change (PGIC) Score at Weeks 2, 4, and 8 | The PGIC is a participants' self-reporting measure that reflects their belief about the efficacy of treatment. It is a 7-point scale where participants rate the questions as: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The lower score indicates improvement. | Weeks 2, 4 and 8 | 
| VC Period: Percentage of Participants With Each Score on the PGIC at Weeks 2, 4, and 8 | The PGIC is a participants' self-reporting measure that reflects their belief about the efficacy of treatment. It is a 7-point scale where participants rate the questions as: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The lower score indicates improvement. | Weeks 2, 4 and 8 | 
| VC Period: Percentage of Participants With a Score of Either 1 or 2 on the PGIC at Weeks 2, 4, and 8 | The PGIC is a participants' self-reporting measure that reflects their belief about the efficacy of treatment. It is a 7-point scale where participants rate the questions as: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse. The lower score indicates improvement. | Weeks 2, 4 and 8 | 
| VC Period: Change From Baseline in EuroQuality of Life Five Dimensions (EQ-5D-5L) Visual Analogue Scale (VAS) Score | EQ-5D-5L questionnaire has 2 parts: EQ-5D-5L descriptive system & EQ-VAS. EQ-5D is a validated, self-administered, generic utility questionnaire wherein participants rate their current health state based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. 5L indicates that for each dimension, there are 5 levels:1=no problems,2=slight problems,3=moderate problems,4=severe problems, and 5=extreme problems. EQ-5D-5L score is assessed using VAS that ranges from 0 to 100 millimetres (mm), where 0 indicates worst health you can imagine and 100 indicates best health you can imagine. The participant was asked to indicate his/her health state over past 7 days in each of the 5 dimensions. Digits for the 5 dimensions can be combined into a 5-digit number that describes the participant's health state. In the EQ-VAS, participants had to record their health state on a scale ranging from 0 to 100. A positive change from Baseline indicates improvement. | Baseline, Weeks 2, 4 and 8 | 
| VC Period: Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) Version 2.0 (v2.0) | The WPAI-SHP is a 6-item participant questionnaire developed to measure the effect of overall health and specific symptoms on productivity at work and regular activities outside of it in the past 7 days. The WPAI-SHP consists of 6 questions as follows: 1=currently employed; 2=hours missed due to AD; 3=hours missed other reasons; 4=hours actually worked; 5=degree AD affected productivity while working; 6=degree AD affected regular activities and the computed percentage, range for each sub scale is from 0 to 100, with higher values indicating greater impairment and less productivity. A negative change from Baseline indicates improvement. | Baseline, Weeks 2, 4, and 8 | 
| LTS Period: Change From Baseline in WPAI-SHP v2.0 | The WPAI-SHP is a 6-item participant questionnaire developed to measure the effect of overall health and specific symptoms on productivity at work and regular activities outside of it in the past 7 days. The WPAI-SHP consists of 6 questions as follows: 1=currently employed; 2=hours missed due to AD; 3=hours missed other reasons; 4=hours actually worked; 5=degree AD affected productivity while working; 6=degree AD affected regular activities and the computed percentage, range for each sub scale is from 0 to 100, with higher values indicating greater impairment and less productivity. A negative change from Baseline indicates improvement. | Baseline, Weeks 12, 24, 36, and 52 | 
| VC Period: Trough Plasma Concentrations of Ruxolitinib | Plasma samples were collected just before the morning application of study drug during each specified time point. | Pre-dose at Weeks 2, 4 and 8 | 
| LTS Period: Trough Plasma Concentrations of Ruxolitinib | Plasma samples were collected just before the morning application of study drug during each specified time point. | Pre-dose at Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic dermatitis, pruritus, eczema, topical therapy, JAK inhibitor