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

• ClinicalTrials.gov Identifier: NCT03745651
• Recruitment Status: Completed
• First Posted: November 19, 2018
• Results First Posted: December 17, 2021
• Last Update Posted: December 17, 2021
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: November 15, 2018
• First Posted Date: November 19, 2018
• Results First Submitted Date: October 20, 2021
• Results First Posted Date: December 17, 2021
• Last Update Posted Date: December 17, 2021
• Actual Study Start Date: December 20, 2018
• Actual Primary Completion Date: November 18, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 19, 2021)

VC Period: Percentage of Participants Who Achieved Investigator's Global Assessment - Treatment Success (IGA-TS) at Week 8 [ Time Frame: Baseline to 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.

Original Primary Outcome Measures (submitted: November 15, 2018)

Proportion of participants achieving Investigator's Global Assessment Treatment Success (IGA-TS) [ Time Frame: From baseline up to 8 weeks ]

Defined as Investigator's Global Assessment (IGA) score of 0 or 1 with ≥ 2 grade improvement from baseline.

Current Secondary Outcome Measures (submitted: November 19, 2021)

• VC Period: Percentage of Participants Who Achieved Eczema Area and Severity Index 75 (EASI75) at Week 8 [ Time Frame: Baseline to 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.
• VC Period: Percentage of Participants With a ≥ 4-Point Improvement in Itch Numerical Rating Scale (NRS) Score From Baseline to Week 8 [ Time Frame: 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.
• 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 [ Time Frame: Baseline to 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.
• 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 [ Time Frame: Baseline to 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.
• VC Period: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (SAE) [ Time Frame: From date of randomization up to Week 8 ]
  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.
• LTS Period: Percentage of Participants With at Least One TEAE and Treatment Emergent SAE [ Time Frame: From first dose date in LTS Period (Week 8) until last follow-up visit (up to 52 weeks) ]
  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.
• VC Period: Percentage of Participants Who Achieved an IGA-TS at Weeks 2 and 4 [ Time Frame: Baseline to 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.
• VC Period: Percentage of Participants Achieving an IGA of 0 or 1 [ Time Frame: Weeks 2, 4 and 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.
• LTS Period: Percentage of Participants Achieving an IGA of 0 or 1 [ Time Frame: Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 ]
  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.
• VC Period: Percentage of Participants With a ≥ 4-Point Improvement in Itch NRS Score From Baseline to Weeks 2 and 4 [ Time Frame: 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.
• VC Period: Percentage of Participants Who Achieved EASI50 [ Time Frame: Baseline to Weeks 2, 4 and 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 EASI50 responder was defined as a participant achieving 50% or greater improvement from Baseline in EASI score.
• VC Period: Percentage of Participants Who Achieved EASI75 at Weeks 2 and 4 [ Time Frame: Baseline to 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.
• VC Period: Percentage of Participants Who Achieved EASI90 [ Time Frame: Baseline to Weeks 2, 4 and 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 EASI90 responder was defined as a participant achieving 90% or greater improvement from Baseline in EASI score.
• VC Period: Percent Change From Baseline in EASI Score [ Time Frame: Baseline, Weeks 2, 4 and 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. A negative change from Baseline indicates improvement.
• VC Period: Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score [ Time Frame: Baseline, Weeks 2, 4 and 8 ]
  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.
• VC Period: Change From Baseline in Itch NRS Score [ Time Frame: Baseline, Weeks 2, 4 and 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. A negative change from Baseline indicates improvement.
• VC Period: Time to Achieve Itch NRS Score Improvement of at Least 2, 3, or 4 Points [ Time Frame: Up 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. Kaplan-Meier estimation method was used for analyses.
• VC Period: Change From Baseline in Skin Pain NRS Score [ Time Frame: Baseline, Weeks 2, 4 and 8 ]
  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.
• 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 [ Time Frame: 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.
• 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 [ Time Frame: 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.
• VC Period: Change From Baseline in PROMIS Short Form - Sleep Disturbance (8b) 24-Hour Recall Score [ Time Frame: Baseline, Weeks 2, 4 and 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. A negative change from Baseline indicates improvement.
• VC Period: Change From Baseline in PROMIS Short Form - Sleep-Related Impairment (8a) 24-Hour Recall Score [ Time Frame: Baseline, Weeks 2, 4 and 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. A negative change from Baseline indicates improvement.
• LTS Period: Change From Baseline in PROMIS Short Form - Sleep-Related Impairment (8a) 7-Day Recall Score [ Time Frame: Baseline, Weeks 12, 24, and 52 ]
  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.
• LTS Period: Change From Baseline in PROMIS Short Form - Sleep Disturbance (8b) 7-Day Recall Score [ Time Frame: Baseline, Weeks 12, 24, and 52 ]
  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.
• VC Period: Change From Baseline in Atopic Dermatitis Afflicted Percentage of Body Surface Area (%BSA) [ Time Frame: Baseline, Weeks 2, 4 and 8 ]
  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.
• LTS Period: Change From Baseline in Atopic Dermatitis Afflicted %BSA [ Time Frame: Baseline, Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  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.
• VC Period: Change From Baseline in Patient-Oriented Eczema Measure (POEM) Score [ Time Frame: Baseline, Weeks 2, 4 and 8 ]
  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.
• LTS Period: Change From Baseline in POEM Score [ Time Frame: Baseline, Weeks 12, 24 and 52 ]
  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.
• VC Period: Change From Baseline in Dermatology Life Quality Index (DLQI) Score [ Time Frame: Baseline, Weeks 2, 4, and 8 ]
  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.
• LTS Period: Change From Baseline in DLQI Score [ Time Frame: Baseline, Weeks 12, 24, and 52 ]
  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.
• VC Period: Change From Baseline in Children Dermatology Life Quality Index (CDLQI) Score [ Time Frame: Baseline, Weeks 2, 4, and 8 ]
  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.
• LTS Period: Change From Baseline in CDLQI Score [ Time Frame: Baseline, Weeks 12, 24, and 52 ]
  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.
• VC Period: Mean Patient Global Impression of Change (PGIC) Score at Weeks 2, 4, and 8 [ Time Frame: 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.
• VC Period: Percentage of Participants With Each Score on the PGIC at Weeks 2, 4, and 8 [ Time Frame: 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.
• VC Period: Percentage of Participants With a Score of Either 1 or 2 on the PGIC at Weeks 2, 4, and 8 [ Time Frame: 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.
• VC Period: Change From Baseline in EuroQuality of Life Five Dimensions (EQ-5D-5L) Visual Analogue Scale (VAS) Score [ Time Frame: Baseline, Weeks 2, 4 and 8 ]
  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.
• VC Period: Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) Version 2.0 (v2.0) [ Time Frame: Baseline, Weeks 2, 4, and 8 ]
  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.
• LTS Period: Change From Baseline in WPAI-SHP v2.0 [ Time Frame: Baseline, Weeks 12, 24, 36, and 52 ]
  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.
• VC Period: Trough Plasma Concentrations of Ruxolitinib [ Time Frame: Pre-dose at Weeks 2, 4 and 8 ]
  Plasma samples were collected just before the morning application of study drug during each specified time point.
• LTS Period: Trough Plasma Concentrations of Ruxolitinib [ Time Frame: Pre-dose at Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 ]
  Plasma samples were collected just before the morning application of study drug during each specified time point.

Original Secondary Outcome Measures (submitted: November 15, 2018)

• Proportion of participants who achieve EASI75 [ Time Frame: Up to 8 weeks ]
  Defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI) score.
• Proportion of participants with a ≥ 4-point improvement in Itch Numerical Rating Scale (NRS) score [ Time Frame: Up to 8 weeks ]
• Proportion of participants with a clinically meaningful improvement in the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form - Sleep Disturbance (8b - 24-hour recall) score [ Time Frame: Up to 8 weeks ]
• Participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 52 weeks ]
  TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
• Proportion of participants achieving an IGA-TS [ Time Frame: From baseline up to 4 weeks ]
  Defined as IGA score of 0 or 1 with ≥ 2 grade improvement from baseline.
• Proportion of participants achieving an IGA of 0 or 1 at each visit [ Time Frame: Up to 8 weeks ]
• Proportion of participants with a ≥ 4-point improvement in Itch NRS score [ Time Frame: Up to 4 weeks ]
• Proportion of participants who achieve EASI50 at each visit during the vehicle-controlled (VC) period. [ Time Frame: Up to 8 weeks ]
  Defined as ≥ 50% improvement in EASI score.
• Proportion of participants who achieve EASI75 [ Time Frame: Up to 4 weeks ]
  Defined as ≥ 75% improvement in EASI score.
• Proportion of participants who achieve EASI90 at each visit during the VC period [ Time Frame: Up to 8 weeks ]
  ≥ 90% improvement in EASI score.
• Mean percentage change from baseline in EASI score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
• Mean percentage change from baseline in SCORAD score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
  SCORing Atopic Dermatitis - tool used to assess extent and severity (intensity) of eczema.
• Change from baseline in Itch NRS score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
• Time to achieve Itch NRS score improvement of at least 2, 3, or 4 points [ Time Frame: Up to 8 weeks ]
• Change from baseline in Skin Pain NRS score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
• Proportion of participants with a clinically meaningful improvement in the PROMIS Short Form - Sleep-Related Impairment (8a) 24-hour recall score [ Time Frame: Up to 8 weeks ]
• Change from baseline in PROMIS Short Form - Sleep Related Impairment (8a) 24-hour recall and Short Form - Sleep Disturbance (8b) 24-hour recall score [ Time Frame: From baseline up to 8 weeks ]
• PROMIS Short Form - Sleep-Related Impairment (8a) 7-day recall and Short Form - Sleep Disturbance (8b) 7-day recall score [ Time Frame: Up to 52 weeks ]
• Change from baseline in AD afflicted percentage of body surface area (%BSA) at every visit [ Time Frame: From baseline up to 52 weeks ]
• Change from baseline in Patient-Oriented Eczema Measure (POEM) score at each visit [ Time Frame: From baseline up to 52 weeks ]
• Change from baseline in Dermatology Life Quality Index (DLQI) score [ Time Frame: From baseline up to 52 weeks ]
• Mean Patient Global Impression of Change (PGIC) score [ Time Frame: Up to 8 weeks ]
• Proportion of participants with each score on the PGIC [ Time Frame: Up to 8 weeks ]
• Proportion of participants with a score of either 1 or 2 on the PGIC [ Time Frame: Up to 8 weeks ]
• Change from baseline in EQ-5D-5L score during the VC period [ Time Frame: From baseline up to 8 weeks ]
  EQ-5D is a validated, self-administered, generic, utility questionnaire wherein participants will rate their current health state based on the following criteria: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
• Change from baseline in WPAI-SHP v2.0 [ Time Frame: From baseline up to 52 weeks ]
  Work Productivity and Activity Impairment Questionnaire: Specific Health Problem Version 2.0.
• Trough plasma concentrations of ruxolitinib at all study visits [ Time Frame: Up to 52 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: TRuE AD2 - An Efficacy and Safety Study of Ruxolitinib Cream in Adolescents and Adults With Atopic Dermatitis
• Official Title: 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
• Brief Summary: The purpose of this study is to assess the efficacy of ruxolitinib cream in adolescents and adults with atopic dermatitis (AD).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis

Intervention

• Drug: Ruxolitinib cream
  Ruxolitinib 0.75% or 1.5% cream.
  Other Name: INCB018424 phosphate cream
• Drug: Vehicle cream
  Ruxolitinib matching vehicle cream.

Study Arms

• Placebo Comparator: Vehicle Control (VC) Period: Vehicle Cream BID
  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.
  Intervention: Drug: Vehicle cream
• Experimental: VC Period: Ruxolitinib 0.75% Cream BID
  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.
  Intervention: Drug: Ruxolitinib cream
• Experimental: VC Period: Ruxolitinib 1.5% Cream BID
  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.
  Intervention: Drug: Ruxolitinib cream
• Experimental: Long-Term Safety (LTS) Period: Vehicle Cream to Ruxolitinib 0.75% Cream BID
  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.
  Intervention: Drug: Ruxolitinib cream
• Experimental: LTS Period: Vehicle Cream to Ruxolitinib 1.5% Cream BID
  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.
  Intervention: Drug: Ruxolitinib cream
• Experimental: LTS Period: Ruxolitinib 0.75% Cream BID
  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.
  Intervention: Drug: Ruxolitinib cream
• Experimental: LTS Period: Ruxolitinib 1.5% Cream BID
  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.
  Intervention: Drug: Ruxolitinib cream

Publications *

• Bloudek L, Eichenfield LF, Silverberg JI, Joish VN, Lofland JH, Sun K, Augustin M, Migliaccio-Walle K, Sullivan SD. Impact of Ruxolitinib Cream on Work Productivity and Activity Impairment and Associated Indirect Costs in Patients with Atopic Dermatitis: Pooled Results From Two Phase III Studies. Am J Clin Dermatol. 2023 Jan;24(1):109-117. doi: 10.1007/s40257-022-00734-8. Epub 2022 Oct 20.
• Gong X, Chen X, Kuligowski ME, Liu X, Liu X, Cimino E, McGee R, Yeleswaram S. Pharmacokinetics of Ruxolitinib in Patients with Atopic Dermatitis Treated With Ruxolitinib Cream: Data from Phase II and III Studies. Am J Clin Dermatol. 2021 Jul;22(4):555-566. doi: 10.1007/s40257-021-00610-x. Epub 2021 May 12.
• Papp K, Szepietowski JC, Kircik L, Toth D, Eichenfield LF, Leung DYM, Forman SB, Venturanza ME, Sun K, Kuligowski ME, Simpson EL. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021 Oct;85(4):863-872. doi: 10.1016/j.jaad.2021.04.085. Epub 2021 May 4.
• Scuron MD, Fay BL, Connell AJ, Peel MT, Smith PA. Ruxolitinib Cream Has Dual Efficacy on Pruritus and Inflammation in Experimental Dermatitis. Front Immunol. 2021 Feb 15;11:620098. doi: 10.3389/fimmu.2020.620098. eCollection 2020.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 1, 2019): 618
• Original Estimated Enrollment (submitted: November 15, 2018): 600
• Actual Study Completion Date: November 9, 2020
• Actual Primary Completion Date: November 18, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Canada, Czechia, Germany, Poland, Spain, United States

Administrative Information

• NCT Number: NCT03745651
• Other Study ID Numbers: INCB 18424-304; 2018-003713-18 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Michael E. Kuligowski, MD, PhD, MBA; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: November 2021