MedPath

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

Phase 3
Completed
Conditions
Atopic Dermatitis
Interventions
Drug: Vehicle Cream
Registration Number
NCT04921969
Lead Sponsor
Incyte Corporation
Brief Summary

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%).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
330
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Vehicle CreamVehicle CreamVehicle cream will be administered twice daily.
Ruxolitinib (0.75% cream)RuxolitinibStudy drug will be administered twice daily.
Ruxolitinib (1.5% Cream)RuxolitinibStudy drug will be administered twice daiily.
Primary Outcome Measures
NameTimeMethod
VC Period: Percentage of Participants Who Achieved Investigator's Global Assessment - Treatment Success (IGA-TS) at Week 8Baseline to 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.

Secondary Outcome Measures
NameTimeMethod
VC Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)from Baseline up to Week 8

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.

LTS Period: Number of Participants With Any TEAEFrom Week 8 up to Week 56

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.

VC Period: Percentage of Participants Who Achieved IGA-TS at Weeks 2 and 4Baseline to 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.

VC Period: Percentage of Participants With a ≥4-Point Improvement in Itch Numerical Rating Scale (NRS) Score From Baseline to Week 8Baseline 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.

VC Period: Percentage of Participants With a ≥4-Point Improvement in Itch NRS Score From Baseline to Day 7 (Week 1)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.

VC Period: Percentage of Participants With a ≥4-Point Improvement in Itch NRS Score From Baseline to Day 3Baseline 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.

VC Period: Percentage of Participants With a ≥4-Point Improvement in Itch NRS Score From Baseline to Week 2 and 4Baseline to Weeks 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.

VC Period: Number of Participants With Any Grade 3 or Higher TEAEfrom Baseline up to Week 8

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.

LTS Period: Number of Participants With Any Grade 3 or Higher TEAEFrom Week 12 up to Week 56

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.

VC Period: Percentage of Participants Who Achieved Eczema Area and Severity Index 75 (EASI75) at Weeks 2, 4, and 8Baseline to 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.

VC Period: Time to Achieve Itch NRS Score Improvement of at Least 2 or 4 Pointsup 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 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.

Trial Locations

Locations (67)

Ohio Pediatric Research Association

🇺🇸

Dayton, Ohio, United States

Velocity Clinical Research Grants Pass Clinical Research Institute of Southern Oregon Pc

🇺🇸

Grants Pass, Oregon, United States

Penn State Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

New York University Langone Medical Center-Fink Children'S Ambulatory Care Center

🇺🇸

New York, New York, United States

Cyn3Rgy Research-Clinedge-Ppds

🇺🇸

Gresham, Oregon, United States

Dr Bobby Buka, Md Greenwich Village

🇺🇸

New York, New York, United States

Velocity Clinical Research-Medford

🇺🇸

Medford, Oregon, United States

Madera Family Medical Group

🇺🇸

Madera, California, United States

Northwestern Memorial Hospital-Arkes Pavilion

🇺🇸

Chicago, Illinois, United States

Dawes Fretzin Clinical Research Group Llc

🇺🇸

Indianapolis, Indiana, United States

Pediatric Center of Excellence Pce Miami Pediatric Endocrinology, Llc

🇺🇸

Miami, Florida, United States

The Childrens Skin Center Csc Miami

🇺🇸

Miami, Florida, United States

Kansas City Dermatology P.A.

🇺🇸

Lenexa, Kansas, United States

University of Southern California

🇺🇸

Los Angeles, California, United States

Progressive Clinical Research

🇺🇸

San Antonio, Texas, United States

Texas Dermatology Alamo Heights Office

🇺🇸

San Antonio, Texas, United States

Knight Cancer Institute At Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

Oregon Dermatology and Research Center

🇺🇸

Portland, Oregon, United States

Skin Specialists Pc the Advanced Skin Research Center

🇺🇸

Omaha, Nebraska, United States

Children'S Hospital of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Palmtree Clinical Research-Clinedge-Ppds

🇺🇸

Palm Springs, California, United States

First Oc Dermatology

🇺🇸

Fountain Valley, California, United States

Clinical Research Center of Alabama

🇺🇸

Birmingham, Alabama, United States

Cct Research With Center For Dermatology and Plastic Surgery

🇺🇸

Scottsdale, Arizona, United States

Cahaba Dermatology

🇺🇸

Hoover, Alabama, United States

Physicians Research Group Ii

🇺🇸

Gilbert, Arizona, United States

Iact Health

🇺🇸

Los Angeles, California, United States

Burke Pharmaceutical Research

🇺🇸

Hot Springs National Park, Arkansas, United States

Metropolis Dermatology

🇺🇸

Los Angeles, California, United States

Integrated Research of Inland, Inc

🇺🇸

Riverside, California, United States

Allergy & Asthma Associates of Southern California

🇺🇸

Mission Viejo, California, United States

Clinical Science Institute Clinical Research Specialists Inc

🇺🇸

Santa Monica, California, United States

Phdermatology

🇺🇸

Clearwater, Florida, United States

Life Clinical Trials Margate

🇺🇸

Margate, Florida, United States

Acevedo Clinical Research

🇺🇸

Miami, Florida, United States

Entrust Clinical Research

🇺🇸

Miami, Florida, United States

Ciocca Dermatology Pa

🇺🇸

Miami, Florida, United States

Aeroallergy Research Lab of Savannah

🇺🇸

Savannah, Georgia, United States

Sneeze Wheeze and Itch Associates Llc

🇺🇸

Normal, Illinois, United States

Northshore Medical Group Dermatology Skokie

🇺🇸

Skokie, Illinois, United States

Dermatology Specialists Research Indiana

🇺🇸

Clarksville, Indiana, United States

Office of Michael W. Simon, Md

🇺🇸

Nicholasville, Kentucky, United States

Meridian Clinical Research

🇺🇸

Baton Rouge, Louisiana, United States

Delricht Clinical Research-Clinedge-Ppds Baton Rouge

🇺🇸

Baton Rouge, Louisiana, United States

Lawrence J. Green, Md. Llc

🇺🇸

Rockville, Maryland, United States

Henry Ford Medical Center-New Center One

🇺🇸

Detroit, Michigan, United States

Michigan Dermatology Institute

🇺🇸

Waterford, Michigan, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

International Clinical Research Tennessee Llc

🇺🇸

Murfreesboro, Tennessee, United States

Arlington Research Center

🇺🇸

Arlington, Texas, United States

Springville Dermatology

🇺🇸

Springville, Utah, United States

Allergy and Asthma Care of Waco, Pa

🇺🇸

Waco, Texas, United States

Intermountain Clinical Research Icr Draper

🇺🇸

Draper, Utah, United States

Skindc Clinic

🇺🇸

Arlington, Virginia, United States

Pi Coor Clinical Research Llc

🇺🇸

Burke, Virginia, United States

Jordan Valley Dermatology Center

🇺🇸

West Jordan, Utah, United States

Dermatology Specialists of Spokane

🇺🇸

Spokane, Washington, United States

Dermatology Research Institute

🇨🇦

Calgary, Alberta, Canada

Leader Research

🇨🇦

Hamilton, Ontario, Canada

Dermatology Ottawa Research Centre

🇨🇦

Ottawa, Ontario, Canada

Dermatology Research Associates

🇺🇸

Los Angeles, California, United States

Coastal Pediatric Associates

🇺🇸

Charleston, South Carolina, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Clinical Research Partners Llc

🇺🇸

Richmond, Virginia, United States

Forcare Clinical Research

🇺🇸

Tampa, Florida, United States

Delricht Research-Touro Medical Center

🇺🇸

New Orleans, Louisiana, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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