The Purpose of the Study is to Evaluate the Effect of Ruxolitinib Cream on Itch in Participants With Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effect of ruxolitinib cream on itch in participants with Atopic Dermatitis.

Official Title
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An Open-Label, Single-Arm Study to Evaluate the Effect of Ruxolitinib 1.5% Cream on Itch in Adult Participants With Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: ruxolitinib cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has clinically confirmed diagnosis of active AD for at least a 6-months. Participant has chronic pruritus related to AD for at least 3 months . Participant has an overall BSA (excluding palms, soles, scalp, genitals, and folds) affected by AD of 1%-20% on Day 1. Participant has an IGA score of at least 2 on Day 1. Participant has a single PP-NRS score ≥ 4 in the 24-hour period prior to the screening visit. Willingness to avoid pregnancy or fathering children. Participant must be willing to comply with all study procedures and restrictions including discontinuation of all current therapies for AD and pruritus (unless otherwise specified), and must be available for the duration of the study. Exclusion Criteria: Female participnat who is breastfeeding, pregnant, or planning to become pregnant during the study. Participant had significant flares or unstable course in AD. Participant has clinically infected AD or has used antibiotics (systemic or topical) for their infected AD within 2 weeks prior to the run-in period. Participant has a history of skin disease or presence of skin condition that, in the opinion of the investigator, would interfere with the study assessments. Participant has any clinically significant medical condition or physical/laboratory/vital sign abnormality that would, in the opinion of the investigator, put the participant at undue risk or interfere with interpretation of study results. Participant has received treatment with JAK inhibitors (systemic or topical) within 4 weeks prior to the run-in period. Participant is unlikely, in the opinion of the investigator, to be compliant with study procedures and requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group : Ruxolitinib<br>ruxolitinib cream 1.5% will be applied twice daily as a thin film. | Drug: ruxolitinib cream<br>* ruxolitinib cream 1.5% will be applied twice daily as a thin film<br>* Other names: INCB018424;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Peak-Pruritus Numerical Rating Scale (PP-NRS) Score at Day 2 (24-hour Recall Period After First Application) | The intensity of pruritus (itch) was recorded daily using the PP-NRS (24-hour recall period). Participants were asked to assign a numerical score representing their itch at the worst moment during the previous 24 hours on a scale of 0 to 10, with 0 being no itch and 10 being the worst itch imaginable. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the average of all non-missing PP-NRS scores reported during the 7-day run-in period. | Baseline; Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Modified Peak-Pruritus Numerical Rating Scale (mPP-NRS) Score (Current Itch Intensity) at 15 and 30 Minutes Postdose and at 1, 2, 4, 6, and 12 Hours Postdose on Day 1 | On Day 1, participants were asked to evaluate the current intensity of their itch at the time of assessment (i.e., prior to the morning study drug application, and 15 and 30 minutes and 1, 2, 4, 6, and 12 hours after the morning study drug application; the 12-hour evaluation occurred prior to the second daily study drug application) on a scale from 0 to 10, with 0 indicating no itch and 10 indicating the worst imaginable itch. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last non-missing assessment before or on Day 1 and prior to the first application of study drug (including unscheduled assessments). | Baseline; Day 1 (15 and 30 minutes postdose; 1, 2, 4, 6, and 12 hours postdose) | 
| Change From Baseline in the PP-NRS Score From Day 3 Through Day 29 (24-hour Recall Period After First Application) | The intensity of pruritus (itch) was recorded daily using the PP-NRS (24-hour recall period). Participants were asked to assign a numerical score representing their itch at the worst moment during the previous 24 hours on a scale of 0 to 10, with 0 being no itch and 10 being the worst itch imaginable. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the average of all non-missing PP-NRS scores reported during the 7-day run-in period. | Baseline; Day 3 through Day 29 | 
| Percentage of Participants Achieving at Least a 1-grade Decrease From Baseline in the mPP-NRS Score at 15 and 30 Minutes Postdose and at 1, 2, 4, 6, and 12 Hours Postdose on Day 1 | On Day 1, participants were asked to evaluate the current intensity of their itch at the time of assessment (i.e., prior to the morning study drug application, and 15 and 30 minutes and 1, 2, 4, 6, and 12 hours after the morning study drug application; the 12-hour evaluation occurred prior to the second daily study drug application) on a scale from 0 to 10, with 0 indicating no itch and 10 indicating the worst imaginable itch. Baseline was defined as the last non-missing assessment before or on Day 1 and prior to the first application of study drug (including unscheduled assessments). Confidence intervals were calculated using the Clopper-Pearson method. | Baseline; Day 1 (15 and 30 minutes postdose; 1, 2, 4, 6, and 12 hours postdose) | 
| Percentage of Participants Achieving at Least a 1-grade Decrease From Baseline in the PP-NRS Score From Day 2 Through Day 29 | The intensity of pruritus (itch) was recorded daily using the PP-NRS (24-hour recall period). Participants were asked to assign a numerical score representing their itch at the worst moment during the previous 24 hours on a scale of 0 to 10, with 0 being no itch and 10 being the worst itch imaginable. Baseline was defined as the average of all non-missing PP-NRS scores reported during the 7-day run-in period. | Baseline; Day 2 through Day 29 | 
| Percentage of Participants Achieving at Least a 2-grade Decrease From Baseline in the mPP-NRS Score at 15 and 30 Minutes Postdose and at 1, 2, 4, 6, and 12 Hours Postdose on Day 1 | On Day 1, participants were asked to evaluate the current intensity of their itch at the time of assessment (i.e., prior to the morning study drug application, and 15 and 30 minutes and 1, 2, 4, 6, and 12 hours after the morning study drug application; the 12-hour evaluation occurred prior to the second daily study drug application) on a scale from 0 to 10, with 0 indicating no itch and 10 indicating the worst imaginable itch. Baseline was defined as the last non-missing assessment before or on Day 1 and prior to the first application of study drug (including unscheduled assessments). | Baseline; Day 1 (15 and 30 minutes postdose; 1, 2, 4, 6, and 12 hours postdose) | 
| Percentage of Participants Achieving at Least a 2-grade Decrease From Baseline in the PP-NRS Score From Day 2 Through Day 29 | The intensity of pruritus (itch) was recorded daily using the PP-NRS (24-hour recall period). Participants were asked to assign a numerical score representing their itch at the worst moment during the previous 24 hours on a scale of 0 to 10, with 0 being no itch and 10 being the worst itch imaginable. Baseline was defined as the average of all non-missing PP-NRS scores reported during the 7-day run-in period. | Baseline; Day 2 through Day 29 | 
| Time to Minimal Clinically Important Difference (MCID) for PP-NRS (≥2-grade Reduction in PP-NRS From Baseline ) | The MCID corresponds to an achievement of a ≥2-grade reduction in PP-NRS from Baseline. The time to MCID was defined as the time from the date (time) of the first dose to the date (time) of the first occurrence of MCID. Baseline was defined as the average of all non-missing PP-NRS scores reported during the 7-day run-in period. | from Baseline up to Day 29 | 
| Time to MCID for mPP-NRS (≥2-grade Reduction in mPP-NRS From Baseline) | The MCID corresponds to an achievement of a ≥2-grade reduction in mPP-NRS from Baseline. The time to MCID was defined as the time from the date (time) of the first dose to the date (time) of the first occurrence of MCID. Baseline was defined as the last non-missing assessment before or on Day 1 and prior to the first application of study drug (including unscheduled assessments). | Baseline; Day 1 | 
| Change From Baseline in Investigator Global Assessment (IGA) at Day 8, Day 15, and Day 29 | The IGA of the current state of the disease is a 5-point morphological assessment of overall disease severity. 0, clear: no erythema or induration/papulation, no oozing/crusting; there may be minor residual discoloration. 1, almost clear: there may be trace faint pink erythema with almost no induration/papulation and no oozing/crusting. 2, mild: there may be faint pink erythema with mild induration/papulation and no oozing/crusting. 3, moderate: there may be pink-red erythema with moderate induration/papulation, and there may be some oozing/crusting. 4, severe: there may be deep or bright red erythema with severe induration/papulation and with oozing/crusting. | Baseline; Days 8, 15, and 29 | 
| Percentage of Participants Achieving Investigator Global Assessment-Treatment Success (IGA-TS) (Score of 0 or 1 in IGA With a ≥2-grade Reduction From Baseline) at Day 8, Day 15, and Day 29 | The IGA-TS is defined as an IGA score of 0 or 1 with a ≥2-grade reduction from Baseline. The IGA of the current state of the disease is a 5-point morphological assessment of overall disease severity. 0, clear: no erythema or induration/papulation, no oozing/crusting; there may be minor residual discoloration. 1, almost clear: there may be trace faint pink erythema with almost no induration/papulation and no oozing/crusting. 2, mild: there may be faint pink erythema with mild induration/papulation and no oozing/crusting. 3, moderate: there may be pink-red erythema with moderate induration/papulation, and there may be some oozing/crusting. 4, severe: there may be deep or bright red erythema with severe induration/papulation and with oozing/crusting. | Baseline; Days 8, 15, and 29 | 
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. TEAEs were defined as any AEs with an onset date during or after the first study treatment dose. | up to Day 43 | 
| Number of Participants With Any Grade 3 or Higher TEAE | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. TEAEs were defined as any AEs with an onset date during or after the first study treatment dose. The severity of AEs were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal. | up to Day 43 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ruxolitinib, Itch, Chronic Pruritus