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

Atopic Dermatitis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04921969
• Other study ID #: INCB 18424-305
• Status: Completed
• Phase: Phase 3
• Start date: July 19, 2021
• Est. completion date: April 8, 2024

Study information

• Verified date: June 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: April 8, 2024
• Est. primary completion date: May 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 11 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Ruxolitinib
The study cream will be applied topically twice a day for up to 52 weeks.
• Vehicle Cream
Matching vehicle cream will be applied topically twice a day for up to 8 weeks.

Locations

Country	Name	City	State
Canada	Dermatology Research Institute	Calgary	Alberta
Canada	Leader Research	Hamilton	Ontario
Canada	Dermatology Ottawa Research Centre	Ottawa	Ontario
United States	Arlington Research Center	Arlington	Texas
United States	Skindc Clinic	Arlington	Virginia
United States	Delricht Clinical Research-Clinedge-Ppds Baton Rouge	Baton Rouge	Louisiana
United States	Meridian Clinical Research	Baton Rouge	Louisiana
United States	Clinical Research Center of Alabama	Birmingham	Alabama
United States	Pi Coor Clinical Research Llc	Burke	Virginia
United States	Coastal Pediatric Associates	Charleston	South Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern Memorial Hospital-Arkes Pavilion	Chicago	Illinois
United States	Dermatology Specialists Research Indiana	Clarksville	Indiana
United States	Phdermatology	Clearwater	Florida
United States	Ohio Pediatric Research Association	Dayton	Ohio
United States	Henry Ford Medical Center-New Center One	Detroit	Michigan
United States	Intermountain Clinical Research Icr Draper	Draper	Utah
United States	First Oc Dermatology	Fountain Valley	California
United States	Physicians Research Group Ii	Gilbert	Arizona
United States	Velocity Clinical Research Grants Pass Clinical Research Institute of Southern Oregon Pc	Grants Pass	Oregon
United States	Cyn3Rgy Research-Clinedge-Ppds	Gresham	Oregon
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Cahaba Dermatology	Hoover	Alabama
United States	Burke Pharmaceutical Research	Hot Springs National Park	Arkansas
United States	Dawes Fretzin Clinical Research Group Llc	Indianapolis	Indiana
United States	Kansas City Dermatology P.A.	Lenexa	Kansas
United States	Dermatology Research Associates	Los Angeles	California
United States	Iact Health	Los Angeles	California
United States	Metropolis Dermatology	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Madera Family Medical Group	Madera	California
United States	Life Clinical Trials Margate	Margate	Florida
United States	Velocity Clinical Research-Medford	Medford	Oregon
United States	Acevedo Clinical Research	Miami	Florida
United States	Ciocca Dermatology Pa	Miami	Florida
United States	Entrust Clinical Research	Miami	Florida
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	Children'S Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Allergy & Asthma Associates of Southern California	Mission Viejo	California
United States	International Clinical Research Tennessee Llc	Murfreesboro	Tennessee
United States	Delricht Research-Touro Medical Center	New Orleans	Louisiana
United States	Dr Bobby Buka, Md Greenwich Village	New York	New York
United States	New York University Langone Medical Center-Fink Children'S Ambulatory Care Center	New York	New York
United States	Office of Michael W. Simon, Md	Nicholasville	Kentucky
United States	Sneeze Wheeze and Itch Associates Llc	Normal	Illinois
United States	Skin Specialists Pc the Advanced Skin Research Center	Omaha	Nebraska
United States	Palmtree Clinical Research-Clinedge-Ppds	Palm Springs	California
United States	Knight Cancer Institute At Oregon Health and Science University	Portland	Oregon
United States	Oregon Dermatology and Research Center	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Clinical Research Partners Llc	Richmond	Virginia
United States	Integrated Research of Inland, Inc	Riverside	California
United States	Mayo Clinic	Rochester	Minnesota
United States	Lawrence J. Green, Md. Llc	Rockville	Maryland
United States	Progressive Clinical Research	San Antonio	Texas
United States	Texas Dermatology Alamo Heights Office	San Antonio	Texas
United States	Clinical Science Institute Clinical Research Specialists Inc	Santa Monica	California
United States	Aeroallergy Research Lab of Savannah	Savannah	Georgia
United States	Cct Research With Center For Dermatology and Plastic Surgery	Scottsdale	Arizona
United States	Northshore Medical Group Dermatology Skokie	Skokie	Illinois
United States	Dermatology Specialists of Spokane	Spokane	Washington
United States	Springville Dermatology	Springville	Utah
United States	Forcare Clinical Research	Tampa	Florida
United States	Allergy and Asthma Care of Waco, Pa	Waco	Texas
United States	Michigan Dermatology Institute	Waterford	Michigan
United States	Jordan Valley Dermatology Center	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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 the first dose date in the LTS Period (Week 8) until the last follow-up visit (up to 52 weeks)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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