A Study to Assess the Efficacy and Safety of Ruxolitinib Cream in Children With Atopic Dermatitis (TRuE-AD3)

A Phase 3, Double-Blind, Randomized, Vehicle-Controlled, Efficacy and Safety Study of Ruxolitinib Cream Followed by a Long-Term Safety Extension Period in Children (Ages≥ 2 Years to < 12 Years) With Atopic Dermatitis ((TRuE-AD3)

The purpose of the study is to assess the efficacy and safety of ruxolitinib cream in children with Atopic Dermatitis. This is a randomized, double-blind, Vehicle Controlled study. Participants will be randomized 2:2:1 to blinded treatment with ruxolitinib cream 0.75% ,1.5% , or vehicle cream, with stratification by baseline IGA score and age. At Week 8, efficacy will be evaluated. Participants who complete Week 8 assessments with no additional safety concerns will continue into the 44-week Long Term Safety (LTS) period with the same treatment regimen, except those initially randomized to vehicle cream will be rerandomized (1:1) in a blinded manner to 1 of the 2 active treatment groups (ruxolitinib cream 0.75% or 1.5%).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 330
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3A 2N1
      • Dermatology Research Institute
  • Ontario
    • Hamilton, Ontario, Canada, L8L 3C3
      • LEADER research
    • Ottawa, Ontario, Canada, K2C 3N2
      • Dermatology Ottawa Research Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Clinical Research Center of Alabama
    • Hoover, Alabama, United States, 35244
      • Cahaba Dermatology
  • Arizona
    • Gilbert, Arizona, United States, 85295
      • Physicians Research Group Ii
    • Scottsdale, Arizona, United States, 85260
      • Cct Research With Center For Dermatology and Plastic Surgery
  • Arkansas
    • Hot Springs National Park, Arkansas, United States, 71913
      • Burke Pharmaceutical Research
  • California
    • Fountain Valley, California, United States, 92708
      • First OC Dermatology
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90045
      • Dermatology Research Associates
    • Los Angeles, California, United States, 90017
      • Metropolis Dermatology
    • Los Angeles, California, United States, 90017
      • IACT Health
    • Madera, California, United States, 93637
      • Madera Family Medical Group
    • Mission Viejo, California, United States, 92691
      • Allergy & Asthma Associates of Southern California
    • Palm Springs, California, United States, 92262
      • Palmtree Clinical Research-Clinedge-Ppds
    • Riverside, California, United States, 92506
      • Integrated Research of Inland, Inc
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute Clinical Research Specialists Inc
  • Florida
    • Clearwater, Florida, United States, 33756
      • Phdermatology
    • Margate, Florida, United States, 33063
      • Life Clinical Trials Margate
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research
    • Miami, Florida, United States, 33156
      • Entrust Clinical Research
    • Miami, Florida, United States, 33146
      • Pediatric Center of Excellence Pce Miami Pediatric Endocrinology, Llc
    • Miami, Florida, United States, 33155
      • The Childrens Skin Center Csc Miami
    • Miami, Florida, United States, 33173
      • Ciocca Dermatology Pa
    • Tampa, Florida, United States, 33624
      • Forcare Clinical Research
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Aeroallergy Research Lab of Savannah
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital-Arkes Pavilion
    • Normal, Illinois, United States, 61761
      • Sneeze Wheeze and Itch Associates LLC
    • Skokie, Illinois, United States, 60076
      • NorthShore Medical Group Dermatology Skokie
  • Indiana
    • Clarksville, Indiana, United States, 47129
      • Dermatology Specialists Research Indiana
    • Indianapolis, Indiana, United States, 46250
      • Dawes Fretzin Clinical Research Group LLC
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Kansas City Dermatology P.A.
  • Kentucky
    • Nicholasville, Kentucky, United States, 40356
      • Office of Michael W. Simon, Md
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Meridian Clinical Research
    • Baton Rouge, Louisiana, United States, 70809
      • Delricht Clinical Research-Clinedge-Ppds Baton Rouge
    • New Orleans, Louisiana, United States, 70115
      • Delricht Research-Touro Medical Center
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Lawrence J. Green, MD. LLC
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Center-New Center One
    • Waterford, Michigan, United States, 48328
      • Michigan Dermatology Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Skin Specialists Pc the Advanced Skin Research Center
  • New York
    • New York, New York, United States, 10012
      • Dr Bobby Buka, Md Greenwich Village
    • New York, New York, United States, 10016
      • New York University Langone Medical Center-Fink Children'S Ambulatory Care Center
  • Ohio
    • Dayton, Ohio, United States, 45414
      • Ohio Pediatric Research Association
  • Oregon
    • Grants Pass, Oregon, United States, 97527
      • Velocity Clinical Research Grants Pass Clinical Research Institute of Southern Oregon Pc
    • Gresham, Oregon, United States, 97030
      • Cyn3Rgy Research-Clinedge-Ppds
    • Medford, Oregon, United States, 97504
      • Velocity Clinical Research-Medford
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology and Research Center
    • Portland, Oregon, United States, 97239
      • Knight Cancer Institute at Oregon Health and Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Associates
  • Tennessee
    • Murfreesboro, Tennessee, United States, 37130
      • International Clinical Research Tennessee Llc
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Research Center
    • San Antonio, Texas, United States, 78213
      • Progressive Clinical Research
    • San Antonio, Texas, United States, 78218
      • Texas Dermatology Alamo Heights Office
    • Waco, Texas, United States, 76712
      • Allergy and Asthma Care of Waco, Pa
  • Utah
    • Draper, Utah, United States, 84020
      • Intermountain Clinical Research Icr Draper
    • Springville, Utah, United States, 84663
      • Springville Dermatology
    • West Jordan, Utah, United States, 84088
      • Jordan Valley Dermatology Center
  • Virginia
    • Arlington, Virginia, United States, 22209
      • Skindc Clinic
    • Burke, Virginia, United States, 22015
      • Pi Coor Clinical Research Llc
    • Richmond, Virginia, United States, 23220
      • Clinical Research Partners LLC
  • Washington
    • Spokane, Washington, United States, 99202
      • Dermatology Specialists of Spokane
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants diagnosed with Atopic Dermatitis (AD) as defined by the Hanifin and Rajka criteria.
• Participants with AD duration of at least 3 months (participant/parent/guardian may verbally report signs and symptoms of AD with onset at least 3 months prior).
• Participants with IGA score of 2 to 3 at the screening and baseline visits.
• Participants with %BSA (excluding scalp) of AD involvement of 3% to 20% at screening and baseline visits.
• For children aged 6 years to < 12 years, baseline itch NRS score ≥ 4.
• Participants/guardians who agree to discontinue all agents used by the participant to treat AD from the screening visit through the final safety follow-up visit.
• Participants with at least 1 target lesion that measures at least 5 cm2 at the screening and baseline visits. The target lesion must be representative of the participant's disease state but not located on the hands, feet, or genitalia.
• Willingness to avoid pregnancy or fathering a child for the duration of study participation.

Exclusion Criteria:

• An unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator over the previous 4 weeks before the baseline visit.

• Concurrent conditions and history of other diseases as follows:

  1. Immunocompromised
  2. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit.
  3. Active acute bacterial, fungal, or viral skin infection within 1 week before the baseline visit.
  4. 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.
  5. 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.
  6. Other types of eczema.
  7. Chronic asthma requiring more than 880 µg of inhaled budesonide or equivalent high dose of other inhaled corticosteroids.
• 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 the baseline visit:

  1. 5 half-lives or 12 weeks, whichever is longer - biologic agents (eg, dupilumab).
  2. 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogues, cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or tacrolimus).
  3. 2 weeks - immunizations with activated vaccines; sedating antihistamines unless on a long-term stable regimen (nonsedating antihistamines are permitted). Note: Live vaccines are not recommended during the VC period.
  4. 1 week - use of topical treatments for AD (other than bland emollients, eg, Aveeno® creams, ointments, sprays, soap substitutes), such as corticosteroids, calcineurin inhibitors, PDE4 inhibitors, coal tar (shampoo), topical 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.
• Participants who have previously received JAK inhibitors, systemic or topical. -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, which is thought by the investigator to potentially impact the participant's AD.-
• Positive serology test results at screening for HIV antibody.
• Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before the baseline visit with another investigational medication or current enrollment in another investigational drug protocol.
• In the opinion of the investigator, unable or unlikely to comply with the administration schedule and study evaluations.
• Employees of the sponsor or investigator or otherwise dependents of them.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ruxolitinib (1.5% Cream); Study drug will be administered twice daiily.	Drug: Ruxolitinib; The study cream will be applied topically twice a day for up to 52 weeks.; Other Names: Jakafi
Experimental: Ruxolitinib (0.75% cream); Study drug will be administered twice daily.	Drug: Ruxolitinib; The study cream will be applied topically twice a day for up to 52 weeks.; Other Names: Jakafi
Placebo Comparator: Vehicle Cream; Vehicle cream will be administered twice daily.	Drug: Vehicle Cream; Matching vehicle cream will be applied topically twice a day for up to 8 weeks.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VC Period: 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 With a ≥4-Point Improvement in Itch Numerical Rating Scale (NRS) Score From Baseline to Week 8	The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity using a diary. Participants were asked to rate the itching severity because of their AD by selecting the 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 ≥4-Point Improvement in Itch NRS Score From Baseline to Day 7 (Week 1)	The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity using a diary. Participants were asked to rate the itching severity because of their AD by selecting the 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 Day 7 (Week 1)
VC Period: Percentage of Participants With a ≥4-Point Improvement in Itch NRS Score From Baseline to Day 3	The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity using a diary. Participants were asked to rate the itching severity because of their AD by selecting the 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 Day 3
VC Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	An adverse event 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 be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study cream. A TEAE is defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up.	from Baseline up to Week 8
VC Period: Number of Participants With Any Grade 3 or Higher TEAE	A TEAE is defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up. The severity of AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: 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.	from Baseline up to Week 8
LTS Period: Number of Participants With Any Grade 3 or Higher TEAE	A TEAE is defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up. The severity of AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: 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.	From Week 12 up to Week 56
VC Period: Percentage of Participants Who Achieved IGA-TS at Weeks 2 and 4	The IGA is an overall eczema severity rating on a 5-point scale ranging from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, induration/papulation, and oozing/crusting. The IGA-TS is defined as an IGA score of 0 (clear skin) or 1 (almost clear skin) with ≥2 grade improvement from Baseline.	Baseline to Weeks 2 and 4
VC Period: Percentage of Participants With a ≥4-Point Improvement in Itch NRS Score From Baseline to Week 2 and 4	The Itch NRS is a daily participant-reported measure (24-hour recall) of the worst level of itch intensity using a diary. Participants 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 described their worst level of itching in the past 24 hours.	Baseline to Weeks 2 and 4
VC Period: Percentage of Participants Who Achieved Eczema Area and Severity Index 75 (EASI75) at Weeks 2, 4, and 8	The EASI scoring system examines 4 areas of the body (head/neck, trunk, upper limbs, and lower limbs) and weights them for participants of ≥8 years of age. Each of the 4 body regions is assessed separately for erythema (E), induration/papulation/edema (I), excoriations (Ex), and lichenification (l), each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72; the severity strata are as follows: 0 = clear; 0.1 to 1.0 = almost clear; 1.1 to 7.0 = mild; 7.1 to 21.0 = moderate; 21.1 to 50.0 = severe; 50.1 to 72.0 = very severe. An EASI75 responder was defined as a participant achieving 75% or greater improvement from Baseline in EASI score.	Baseline to Weeks 2, 4, and 8
VC Period: Time to Achieve Itch NRS Score Improvement of at Least 2 or 4 Points	The Itch NRS is a daily participant-reported measure (24-hour recall), of the worst level of itch intensity using a diary. Participants are asked to rate the itching severity because of their AD by selecting a number from 0 (no itch) to 10 (worst imaginable itch) that best describes their worst level of itching in the past 24 hours. Kaplan-Meier estimation method was used for analyses.	up to Week 8
LTS Period: Number of Participants With Any TEAE	An adverse event 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 be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study cream. A TEAE is defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until the end of the safety follow-up.	From Week 8 up to Week 56

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Brett Angel, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2021
• Primary Completion (Actual): May 10, 2023
• Study Completion (Actual): April 8, 2024

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Ruxolitinib; Atopic Dermatitis
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis, Atopic; Dermatitis; Eczema
• Other Study ID Numbers: INCB 18424-305

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency.

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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