A Study to Evaluate the Efficacy, and Safety Study of Ruxolitinib Cream in Adults With Moderate Atopic Dermatitis

Incyte Corporation241 enrolled

Overview

This study is being conducted to establish the efficacy of ruxolitinib cream in participants with moderate AD who had an inadequate response to, or are intolerant to, or contraindicated to topical corticosteroid (TCS)s and topical calcineurin inhibitor (TCI)s.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

241

Conditions

Atopic Dermatitis

Interventions

Ruxolitinib CreamDRUG

Ruxolitinib cream applied topically to the affected area as a thin film twice daily.

Vehicle CreamDRUG

Matching vehicle cream applied topically to the affected area as a thin film twice daily.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adults aged ≥ 18 years at screening (Note: Legal adult age for Korea is ≥ 19 years). * Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria. * AD duration of at least 2 years. * IGA score of 3 at screening and Day 1. * EASI score \> 7 at screening and Day 1. * Itch NRS score ≥ 4 at Day 1, defined as the average of the 7 days directly before Day 1, with Itch NRS values available for at least 4 of the 7 days. * %BSA (excluding the scalp) with AD involvement of at least 10% and up to 20% at screening and Day 1. * DLQI score \> 10 at screening and Day 1. * Documented recent history (within 12 months before the screening visit) of inadequate response, intolerance, or contraindication to TCSs and TCIs. * Agree to discontinue all agents used to treat AD from screening through the final follow up visit, except as outlined in the protocol. * Willingness to avoid pregnancy or fathering children based on the criteria as outlined in the protocol. Exclusion Criteria: * Unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator in the 4 weeks prior to Day 1. * Concurrent conditions and history of other diseases as follows: * Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich syndrome). * Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before Day 1. * Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chickenpox) within 1 week before Day 1. * Any other concomitant skin disorder (eg, generalized erythroderma, such as Netherton syndrome), 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 classic areas of involvement such as the face or the flexural folds. * Other types of eczema within the 6 months prior to screening. Note: Seborrheic dermatitis on the scalp is allowed, as the scalp will not be treated with study cream. * Current or history of hepatitis B or C virus infection. * 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 cream and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. * Any of the following clinical laboratory test results at screening: * Hemoglobin \< 10 g/dL. * Liver function tests: * AST or ALT ≥ 2 × ULN. * Alkaline phosphatase \> 1.5 × ULN. * Bilirubin \> 1.5 × ULN (isolated bilirubin \> 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%) with the exception of Gilbert's disease. * Estimated glomerular filtration rate \< 30 mL/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology Collaboration equation). * Positive serology test results for HIV antibody. * Any other clinically significant laboratory result that, in the opinion of the investigator, poses a significant risk to the participant. * Use of any of the following treatments within the indicated washout period before Day 1: * 5 half-lives or 12 weeks, whichever is longer: biologic agents. For biologic agents with washout periods longer than 12 weeks (eg, rituximab), consult the medical monitor. * 4 weeks: systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive (eg, JAK inhibitors) or immunomodulating agents (eg, mycophenolate or tacrolimus). * 2 weeks or 5 half-lives, whichever is longer - strong systemic CYP3A4 inhibitors. * 2 weeks: immunizations with live-attenuated vaccines; sedating antihistamines unless on a long-term stable regimen (nonsedating antihistamines are permitted). Note: COVID-19 vaccination is allowed. • 1 week: use of other topical treatments for AD, other than bland emollients (eg, Aveeno creams, ointments, sprays, soap substitutes), such as antipruritics (eg, doxepin cream), corticosteroids, calcineurin inhibitors, PDE4 inhibitors, coal tar (shampoo), antibiotics, or antibacterial cleansing body wash/soap. Note: 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. * History of treatment failure with any systemic or topical JAK inhibitor (eg, ruxolitinib, tofacitinib, baricitinib, abrocitinib, upadacitinib) for AD or any other inflammatory condition. * Ultraviolet light therapy or prolonged exposure to natural or artificial sources of UV radiation (eg, sunlight or tanning booth) within 2 weeks prior to the baseline visit and/or intention to have such exposure during the study that is thought by the investigator to potentially impact the participant's AD. * 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. * In the opinion of the investigator, are unable or unlikely to comply with the administration schedule, study evaluations, and procedures (eg, eDiary compliance). Other protocol-defined Inclusion/Exclusion Criteria may apply.

Locations (94)

Outcomes

Primary Outcomes

VC Period: Proportion of participants who achieved Eczema Area and Severity Index 75 (EASI75)

Defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI) score.

Time frame: Baseline to Week 8

VC Period: Proportion of participants who achieved Investigator's Global Assessment Treatment Success (IGA-TS)

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

Time frame: Baseline to Week 8

Secondary Outcomes

VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)

ITCH4 is defined as achieving ≥ 4-point improvement in Itch NRS score.

Time frame: Baseline to Week 8

VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)

ITCH4 is defined as achieving ≥ 4-point improvement in Itch NRS score.

Time frame: Baseline to Day 7

VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)

ITCH4 is defined as achieving ≥ 4-point improvement in Itch NRS score.

Time frame: Baseline to Day 3

VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)

ITCH4 is defined as achieving ≥ 4-point improvement in Itch NRS score.

Time frame: Baseline to Day 2

VC Period: Number of Treatment Emergent Adverse Events (TEAEs)

Data from ClinicalTrials.gov

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Lynn Institute of the Ozarks

Little Rock, Arkansas, United States

First Oc Dermatology

Fountain Valley, California, United States

Center For Dermatology Cosmetic and Laser Surgery

Fremont, California, United States

Medderm Associates, Inc

San Diego, California, United States

Encore Medical Research, Llc Hollywood

Hollywood, Florida, United States

Entrust Clinical Research

Miami, Florida, United States

Lane Dermatology and Dermatologic Surgery

Columbus, Georgia, United States

Marietta Dermatology the Skin Cancer Center Marietta

Marietta, Georgia, United States

Arlington Dermatology

Rolling Meadows, Illinois, United States

Northshore University Healthsystem

Skokie, Illinois, United States

...and 84 more locations

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.

Time frame: Up to Week 24, followed by 30 days follow-up

VC Period: Proportion of participants who achieved Eczema Area and Severity Index 75 (EASI75)

Defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI) score.

Time frame: Baseline to Weeks 2 and 4

VC Period: Proportion of participants who achieved Investigator's Global Assessment - Treatment Success (IGA-TS)

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

Time frame: Baseline to Weeks 2 and 4

VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)

ITCH4 is defined as achieving ≥ 4-point improvement in Itch NRS score.

Time frame: Baseline to Weeks 2 and 4

VC Period: Time to achieve a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)

ITCH4 is defined as achieving ≥ 4-point improvement in Itch NRS score.

Time frame: Baseline to Week 8

VC Period: Time to achieve ≥ 2-point improvement from in Itch Numeric Rating Scale (NRS) score (ITCH2)

ITCH2 is defined as achieving ≥ 2-point improvement from baseline in Itch NRS score.

Time frame: Baseline to Week 8

VC Period: Change from baseline (pre-study cream application) in current Itch NRS score at 5, 15, 30, 45, and 60 minutes and 2, 4, and 6 hours post-initial dose on Day 1.

Time frame: Baseline to Day 1

VC Period: Proportion of participants achieving at least a 2-point decrease from baseline in current Itch NRS score at 5, 15, 30, 45, and 60 minutes and 2, 4, and 6 hours post-initial dose on Day 1.

Time frame: Baseline to Day 1

VC Period: Proportion of participants achieving at least a 4-point decrease from baseline in current Itch NRS score at 5, 15, 30, 45, and 60 minutes and 2, 4, and 6 hours post-initial dose on Day 1.

Time frame: Baseline to Day 1

VC and VCE Periods: Proportion of participants who achieved EASI50

Defined as ≥ 50% improvement in Eczema Area and Severity Index (EASI) score.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Proportion of participants who achieved EASI90

Defined as ≥ 90% improvement in Eczema Area and Severity Index (EASI) score.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Proportion of participants achieving both EASI75 and IGA-TS

Defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI) score and IGA score of 0 or 1 with ≥ 2 grade improvement from baseline.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Change from Baseline in Atopic Dermatitis Afflicted Percentage of Body Surface Area (%BSA)

A negative change from Baseline indicates improvement.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Change from baseline in EASI score

A negative change from Baseline indicates improvement.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Change from baseline in SCORAD score

SCORing Atopic Dermatitis - tool used to assess extent and severity (intensity) of eczema.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Change from baseline in Itch NRS score

The Itch NRS is an instrument for measurement of itch intensity and participant will rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable).

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Change from baseline in Skin Pain NRS score

The Skin Pain NRS is a daily participant-reported measure (24-hour or 7-day recall) of the worst level of pain intensity from 0 (no pain) to 10 (worst pain imaginable.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VCE Period: Time to open-label escape arm

Defined as not achieving 50% improvement in EASI score from baseline at 2 consecutive visits at least 1 week apart.

Time frame: Baseline to Week 24

VC and VCE Periods: Proportion of participants concurrently meeting all of the following criteria: IGA score ≥ 3, EASI score ≥ 16, Itch NRS score ≥ 4, BSA ≥ 10%, and DLQI score > 10

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Time to concurrently meeting all of the following criteria: IGA score ≥ 3, EASI score ≥ 16, Itch NRS score ≥ 4, BSA ≥ 10%, and DLQI score > 10

Time frame: Baseline to Week 24

VC Period: Proportion of participants who experience a relapse after study treatment discontinuation

Defined as proportion of participants among EASI75 responders who are on study treatment at Week 24 who meet relapse criteria \[loss of EASI50 from baseline\] at the safety follow-up visit.

Time frame: Week 24 to Follow-up (30 days)

VCE period: Time to first re-treatment

Time frame: Week 8 to Week 24

VCE Period: Proportion of time off study treatment due to lesion clearance

Time frame: Week 8 to Week 24

VCE period: Proportion of time on study treatment

Time frame: Week 8 to Week 24

VC and VCE Periods: Proportion of participants who achieve ≥ 4-point improvement in DLQI from baseline

The DLQI is a 10-question validated questionnaire to measure how much the skin problem has affected the participant over the previous 7 days. The participant will answer the questionnaire with either (1) very much, (2) a lot, (3) a little, or (4) not at all. A negative change from Baseline indicates less impact of the skin problem on participant's life.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Change From Baseline in Dermatology Life Quality Index (DLQI) Score

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: 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. A negative change from Baseline indicates improvement.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Change From Baseline in EuroQuality of Life Five Dimensions (EQ-5D-5L) Visual Analogue Scale (VAS) Score

he EQ-5D-5L questionnaire is a standardized, validated instrument for use as a measure of health outcome. The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: Level 1 = no problems, Level 2 = slight problems, Level 3 = moderate problems, Level 4 = severe problems, and Level 5 = extreme problems.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Change from baseline in the HADS scores

The Hospital Anxiety and Depression Scale (HADS) is a 14-item questionnaire to be completed by tablet; the questionnaire assesses the levels of anxiety and depression a person is currently experiencing. There are 7 questions each for measuring anxiety and for measuring depression, with 4 possible responses to each question (responses are scored as 0, 1, 2, or 3). Separate scores are calculated for anxiety and depression. The recall period will be the past 7 days for both the VC and VCE periods.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Change from baseline in PROMIS Short Form - Sleep-Related Impairment (8a) 24-Hour Recall Score

The Patient-Reported Outcomes Measurement Information System (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.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE 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.

Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24

VC and VCE Periods: Change from baseline score in Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD)

The WPAI-AD questionnaire is a validated 6-item instrument that measures the effect of overall health and specific symptoms on productivity at work and regular activities outside of it during the past 7 days.

Time frame: Baseline to Week 8 and Week 24