Topical Ruxolitinib Evaluation in Atopic Dermatitis Study 1 (TRuE AD1) - An Efficacy and Safety Study of Ruxolitinib Cream in Adolescents and Adults With Atopic Dermatitis

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

The purpose of this study is to assess the efficacy and safety of twice daily ruxolitinib cream in adolescents and adults with Atopic Dermatitis (AD).

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Vehicle Cream; Drug: Ruxolitinib Cream

• Study Type: Interventional
• Enrollment (Actual): 631
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Markham, Ontario, Canada, L3P 1X2
      • Lynderm Research Inc
    • Richmond Hill, Ontario, Canada, L4C 9M7
      • York Dermatology Center
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research
    • Windsor, Ontario, Canada, N8W 5L7
      • Windsor Clinical Research Inc.
    • Windsor, Ontario, Canada, N8X 3V6
      • Xlr8 Medical Research
  • Quebec
    • Westmount, Quebec, Canada, H3Z 2S6
      • Siena Medical Reserch Corporation
• France
  • Brest, France, 29609
    • CHRU de Brest - Hopital Morvan
  • Martigues, France, 13500
    • Le Bateau Blanc - Imm. A
  • Nice, France, 06202
    • Hopital L'Archet 2
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rouen, France, 76031
    • Hopital Charles Nicolle
• Germany
  • Frankfurt am Main, Germany, 60590
    • Universitätsklinikum Frankfurt
  • Niedersachsen
    • Buxtehude, Niedersachsen, Germany, 21614
      • Elben Klinken Stade - Buxtehude
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53105
      • Universitätsklinikum Bonn
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitätsklinikum Carl Gustav Carus an der TU Dresden
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitätsklinikum Schleswig-Holstein
• Hungary
  • Budapest, Hungary, 1036
    • Synexus (DRS) - Synexus Magyarország Kft. Budapest
  • Debrecen, Hungary, 4025
    • Synexus Affiliate - Synexus Magyarorszag Kft. Debrecen
  • Gyula, Hungary, 5700
    • Synexus (DRS) - Synexus Magyarország Kft. Gyula
  • Pécs, Hungary, 7632
    • Pecsi Tudomanyegyetem
  • Szolnok, Hungary, 5000
    • Allergo-Derm Bakos Kft.
  • Zalaegerszeg, Hungary, 8900
    • Synexus (DRS) - Synexus Magyarország Kft. Zalaegerszeg
• Italy
  • Roma, Italy, 168
    • Fondazione Policlinico Universitario A Gemelli
• Poland
  • Katowice, Poland, 40-040
    • Synexus - Katowice
  • Krakow, Poland, 30-510
    • Centrum Medyczne Krakow - PRATIA - PPDS
  • Lublin, Poland, 20-412
    • ETG Lublin
  • Poznan, Poland, 60-702
    • Synexus Polska Sp. z o.o. Oddzial w Poznaniu
  • Tarnow, Poland, 33-100
    • ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z.o.o
  • Warsaw, Poland, 02-777
    • ETG Warszawa
  • Warszawa, Poland, 00-874
    • Medycyna Kliniczna Marzena Waszczak-Jeka
  • Warszawa, Poland, 02-962
    • Royalderm
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-381
      • Synexus - Wroclaw
    • Wroclaw, Dolnoslaskie, Poland, 53-658
      • Centrum Medyczne ADAMAR
  • Lódzkie
    • Zgierz, Lódzkie, Poland, 95-100
      • ETG Zgierz
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 02-953
      • Klinika Ambroziak
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-382
      • Synexus - Gdansk
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 70-332
      • Laser Clinic S.C.
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35244
      • Cahaba Dermatology
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
  • California
    • Fountain Valley, California, United States, 92708
      • First OC Dermatology
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Oceanside, California, United States, 92056
      • Dermatology Specialists Inc
    • Riverside, California, United States, 92506
      • Integrated Research Group Inc.
    • Westminster, California, United States, 92683
      • Advanced Rx Clinical Research
  • Florida
    • Boca Raton, Florida, United States, 33433
      • Clearlyderm Boca Raton - BTC - PPDS
    • Largo, Florida, United States, 33770
      • Olympian Clinical Research
    • Miami, Florida, United States, 33143
      • Well Pharma Medical Research Corporation
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research
    • Miami, Florida, United States, 33147
      • AdvancedPharma CR LLC
    • Tampa, Florida, United States, 33613
      • University of South Florida
    • Tampa, Florida, United States, 33624
      • ForCare Clinical Research
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute Inc
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Aeroallergy Research Lab of Savannah
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta - ERN-PPDS
  • Illinois
    • Normal, Illinois, United States, 61761
      • Sneeze Wheeze and Itch Associates Llc
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Dawes Fretzin Clinical Research Group LLC
    • New Albany, Indiana, United States, 47150
      • DS Research
  • Kansas
    • Overland Park, Kansas, United States, 66215
      • Kansas City Dermatology P.A.
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Skin Sciences, PLLC
    • Nicholasville, Kentucky, United States, 40356
      • Michael W Simon MD
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Dermassociates
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Jdr Dermatology Research
  • New York
    • Forest Hills, New York, United States, 11375
      • Forest Hills Dermatology Group
    • New York, New York, United States, 10075
      • Sadick Dermatology
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
  • Ohio
    • Huber Heights, Ohio, United States, 45424
      • Ohio Pediatric Research Assn Inc
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Central Sooner Research
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Cyn3rgy Research - ClinEdge - PPDS
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute Of Southern Oregon - Crisor
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97223
      • Oregon Medical Research Center PC
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Synexus Clinical Research Us Inc. Greer
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research, LLC
  • Texas
    • Carrollton, Texas, United States, 75010
      • Family Medicine Associates of Texas
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research PA
  • Utah
    • West Jordan, Utah, United States, 84088
      • Jordan Valley Medical Center
  • Virginia
    • Burke, Virginia, United States, 22015
      • PI Coor Clinical Research LLC
    • Henrico, Virginia, United States, 23233
      • West End Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 [Vehicle Controlled (VC) Period] and 0 to 4 at Week 8 [Long-Term Safety (LTS) Period].
• Participants with percentage of 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 (eg. dupilumab).
  • 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• Plain Language Summary of Results

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2018
• Primary Completion (Actual): December 23, 2019
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: November 15, 2018
• First Posted (Actual): November 19, 2018

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Atopic Dermatitis; Pruritus; Eczema; Topical Therapy; JAK Inhibitor
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: INCB 18424-303; 2018-003712-45 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No