A Study to Evaluate the Safety and Efficacy of Ruxolitinib Phosphate Cream Applied Topically to Adults With Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to establish the efficacy of each strength of ruxolitinib cream once daily (QD) or twice daily (BID) in participants with atopic dermatitis as compared with vehicle cream BID.

Official Title
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A Phase 2, Randomized, Dose-Ranging, Vehicle-Controlled and Triamcinolone 0.1% Cream-Controlled Study to Evaluate the Safety and Efficacy of INCB018424 Phosphate Cream Applied Topically to Adults With Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Ruxolitinib 0.15% Cream QD
* Drug: Ruxolitinib 0.5% Cream QD
* Drug: Ruxolitinib 1.5% Cream QD
* Drug: Ruxolitinib 1.5% Cream BID
* Drug: Triamcinolone 0.1% Cream BID
* Drug: Vehicle Cream BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants diagnosed with atopic dermatitis (AD) as defined by the Hanifin and Rajka criteria. Participants with a history of AD for at least 2 years. Participants with an Investigator's Global Assessment (IGA) score of 2 to 3 at screening and baseline. Participants with body surface area (BSA) of AD involvement, excluding the face and intertriginous areas, of 3% to 20% at screening and baseline. Participants who agree to discontinue all agents used to treat AD from screening through the final follow-up visit. Exclusion Criteria: Participants with evidence of active acute or chronic infections. Use of topical treatments for AD (other than bland emollients) within 2 weeks of baseline. Systemic immunosuppressive or immunomodulating drugs (eg, oral or injectable corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine) within 4 weeks or 5 half-lives of baseline (whichever is longer). Participants with other dermatologic disease besides AD whose presence or treatments could complicate the assessment of disease (eg, psoriasis). Participants with a history of other diseases besides dermatologic disorders (eg, other autoimmune diseases) taking treatments that could complicate assessments. Participants with cytopenias at screening, defined as: Leukocytes < 3.0 × 10^9/L. Neutrophils < lower limit of normal. Hemoglobin < 10 g/dL. Lymphocytes < 0.8 × 10^9/L Platelets < 100 × 10^9/L. Participants with severely impaired liver function (Child-Pugh Class C) or end-stage renal disease (ESRD) on dialysis or at least 1 of the following: Serum creatinine > 1.5 mg/dL. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 × upper limit of normal. Participants taking potent systemic cytochrome P450 3A4 inhibitors or fluconazole within 2 weeks or 5 half-lives, whichever is longer, before the baseline visit (topical agents with limited systemic availability are permitted). Participants who have previously received Janus kinase (JAK) inhibitors, systemic or topical (e.g., ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, pacritinib).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Double Blind (DB): Vehicle BID<br>Participants applied vehicle cream twice daily (BID) for 8 weeks DB period. | Drug: Vehicle Cream BID<br>* Vehicle cream BID<br>|
| Active Comparator: DB: Triamcinolone (TAC) 0.1% BID/Vehicle Cream BID<br>Participants applied triamcinolone 0.1% cream BID for 4 weeks followed by vehicle cream for 4 weeks in DB period. | Drug: Triamcinolone 0.1% Cream BID<br>* Triamcinolone 0.1% cream BID<br>Drug: Vehicle Cream BID<br>* Vehicle cream BID<br>|
| Experimental: DB: Ruxolitinib 0.15% Once Daily (QD)<br>Participants applied ruxolitinib 0.15% cream QD for 8 weeks in DB period. | Drug: Ruxolitinib 0.15% Cream QD<br>* Ruxolitinib 0.15% cream QD<br>* Other names: INCB018424;|
| Experimental: DB: Ruxolitinib 0.5% QD<br>Participants applied ruxolitinib 0.5% cream QD for 8 weeks in DB period. | Drug: Ruxolitinib 0.5% Cream QD<br>* Ruxolitinib 0.5% cream QD<br>* Other names: INCB018424;|
| Experimental: DB: Ruxolitinib 1.5% QD<br>Participants applied ruxolitinib 1.5% cream QD for 8 weeks in DB period. | Drug: Ruxolitinib 1.5% Cream QD<br>* Ruxolitinib 1.5% cream QD<br>* Other names: INCB018424;|
| Experimental: DB: Ruxolitinib 1.5% BID<br>Participants applied ruxolitinib 1.5% cream BID for 8 weeks in DB period. | Drug: Ruxolitinib 1.5% Cream BID<br>* Ruxolitinib 1.5% cream BID<br>* Other names: INCB018424;|
| Placebo Comparator: Open-Label (OL): Vehicle BID to Ruxolitinib 1.5% BID<br>Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. | Drug: Ruxolitinib 1.5% Cream BID<br>* Ruxolitinib 1.5% cream BID<br>* Other names: INCB018424;|
| Active Comparator: OL: TAC BID/Vehicle BID to Ruxolitinib 1.5% BID<br>Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. | Drug: Ruxolitinib 1.5% Cream BID<br>* Ruxolitinib 1.5% cream BID<br>* Other names: INCB018424;|
| Experimental: OL: Ruxolitinib 0.15% QD to Ruxolitinib 1.5% BID<br>Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. | Drug: Ruxolitinib 1.5% Cream BID<br>* Ruxolitinib 1.5% cream BID<br>* Other names: INCB018424;|
| Experimental: OL: Ruxolitinib 0.5% QD to Ruxolitinib 1.5% BID<br>Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. | Drug: Ruxolitinib 1.5% Cream BID<br>* Ruxolitinib 1.5% cream BID<br>* Other names: INCB018424;|
| Experimental: OL: Ruxolitinib 1.5% QD to Ruxolitinib 1.5% BID<br>Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. | Drug: Ruxolitinib 1.5% Cream BID<br>* Ruxolitinib 1.5% cream BID<br>* Other names: INCB018424;|
| Experimental: OL: Ruxolitinib 1.5% BID to Ruxolitinib 1.5% BID<br>Following DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks. | Drug: Ruxolitinib 1.5% Cream BID<br>* Ruxolitinib 1.5% cream BID<br>* Other names: INCB018424;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 4 in Participants Treated With Ruxolitinib 1.5% Cream Twice a Day (BID) Compared With Participants Treated With Vehicle Cream BID | EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI 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. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement. | Baseline and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage Change From Baseline in EASI Score at Week 4 in Participants Treated With Ruxolitinib QD Compared With Participants Treated With Vehicle Cream BID | EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI 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. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement. | Baseline and Week 4 | 
| Mean Percentage Change From Baseline in EASI Score at Week 4 in Participants Treated With Ruxolitinib QD/BID Cream Compared With Participants Treated With Triamcinolone 0.1% Cream BID Followed by Vehicle | EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI 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. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement. | Baseline and Week 4 | 
| Mean Percentage Change From Baseline in EASI Score at Week 2 and Week 8 | EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI 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. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement. | Baseline, Week 2 and 8 | 
| Percentage of Participants Who Achieve a ≥ 50% Improvement From Baseline in EASI (EASI-50) at Weeks 2, 4, and 8 | The categorical variable EASI-50 will be equal to 1 for percentage improvement from baseline in EASI score of 50% or greater and will be equal to 0 for percentage improvement of less than 50%. This definition is introduced for the purpose of identifying participants who respond to the treatment (1 = responder, 0 = non-responder). | Week 2, 4 and 8 | 
| Percentage Change From Baseline in EASI Score at Week 4 | EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI 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. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement. | Baseline and Week 4 | 
| Time to Achieve EASI-50 | Time to EASI-50 is defined as the interval between the time of randomization and the time of achieving at least 50% improvement in EASI score. | From Baseline to Week 8 | 
| Percentage of Participants Achieving an Investigator's Global Assessment (IGA) Score of 0 to 1 Who Have an Improvement of ≥ 2 Points From Baseline at Weeks 2, 4, and 8 | IGA is an assessment scale used to determine severity of atopic dermatitis (AD) and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). An IGA responder was defined as a participant achieving an IGA score of 0 to 1 and an IGA score improvement at least 2 from baseline. | Week 2, 4 and 8 | 
| Mean Change From Baseline in the Itch Numerical Rating Scale (NRS) Score at Weeks 2, 4, and 8 | The Itch NRS is a once-per-24 hours (daily) participant-reported measure of itch intensity 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. The categorical NRS is defined as 0 = None, 1 to 3 = Mild, 4 to 6 = Moderate, and 7 to 10 = Severe. | Baseline, Week 2, 4 and 8 | 
| Number of Participants With At Least One Adverse Event (AEs) and as Per Severity | AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. The severity of AEs was assessed using CTCAE v4.03 Grades 1 through 4.Data are reported for Grade 3 and higher severity for this outcome measure. | Up to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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eczema, Atopic dermatitis, pruritus, Janus kinase (JAK) inhibitors