TRuE AD2 - An Efficacy and Safety Study of Ruxolitinib Cream in Adolescents and Adults With Atopic Dermatitis

NCT03745651 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: INCB 18424-3042018-003713-18
• Study Type: interventional
• Target: 618
• Locations: 7 countries
• Sites: 66

Brief Summary

The purpose of this study is to assess the efficacy of ruxolitinib cream in adolescents and adults with atopic dermatitis (AD).

Conditions

Atopic Dermatitis

Keywords

Atopic dermatitis; pruritus; eczema; topical therapy; JAK inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (40)

• VC Period: Percentage of Participants Who Achieved Eczema Area and Severity Index 75 (EASI75) at Week 8

  Baseline to Week 8

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

  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 at Week 8

  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) Score at Week 8

  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)

  From date of randomization up to Week 8

Study Arms (7)

Vehicle Control (VC) Period: Vehicle Cream BID

PLACEBO COMPARATOR

Participants received ruxolitinib matching vehicle cream, applied topically to the affected areas as a thin film twice daily (BID) 8 hours apart from Day 1 up to Week 8. Participants applied cream BID to areas identified at Baseline even if the areas improved.

Drug: Vehicle cream

VC Period: Ruxolitinib 0.75% Cream BID

EXPERIMENTAL

Participants received ruxolitinib 0.75% cream, applied topically to the affected areas as a thin film BID 8 hours apart from Day 1 up to Week 8. Participants applied cream BID to areas identified at Baseline even if the areas improved.

Drug: Ruxolitinib cream

VC Period: Ruxolitinib 1.5% Cream BID

EXPERIMENTAL

Participants received ruxolitinib 1.5% cream, applied topically to the affected areas as a thin film BID 8 hours apart from Day 1 up to Week 8. Participants applied cream BID to areas identified at Baseline even if the areas improved.

Drug: Ruxolitinib cream

Long-Term Safety (LTS) Period: Vehicle Cream to Ruxolitinib 0.75% Cream BID

EXPERIMENTAL

Participants who applied vehicle cream during the VC Period were randomized at Week 8 to apply ruxolitinib 0.75% cream, topically to the affected areas as a thin film BID as needed from Week 8 up to Week 52. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence.

Drug: Ruxolitinib cream

LTS Period: Vehicle Cream to Ruxolitinib 1.5% Cream BID

EXPERIMENTAL

Participants who applied vehicle cream during the VC Period were randomized at Week 8 to apply ruxolitinib 1.5% cream, topically to the affected areas as a thin film BID as needed from Week 8 up to Week 52. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence.

Drug: Ruxolitinib cream

LTS Period: Ruxolitinib 0.75% Cream BID

EXPERIMENTAL

Participants who applied ruxolitinib 0.75% cream during the VC Period, continued applying ruxolitinib 0.75% cream, topically to the affected areas as a thin film BID as needed from Week 8 up to Week 52. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence.

Drug: Ruxolitinib cream

LTS Period: Ruxolitinib 1.5% Cream BID

EXPERIMENTAL

Participants who applied ruxolitinib 1.5% cream during the VC Period, continued applying ruxolitinib 1.5% cream, topically to the affected areas as a thin film BID as needed from Week 8 up to Week 52. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence.

Drug: Ruxolitinib cream

Interventions

Ruxolitinib cream DRUG

Ruxolitinib 0.75% or 1.5% cream.

Also known as: INCB018424 phosphate cream

LTS Period: Ruxolitinib 0.75% Cream BID; LTS Period: Ruxolitinib 1.5% Cream BID; LTS Period: Vehicle Cream to Ruxolitinib 1.5% Cream BID; Long-Term Safety (LTS) Period: Vehicle Cream to Ruxolitinib 0.75% Cream BID; VC Period: Ruxolitinib 0.75% Cream BID; VC Period: Ruxolitinib 1.5% Cream BID

Vehicle cream DRUG

Ruxolitinib matching vehicle cream.

Vehicle Control (VC) Period: Vehicle Cream BID

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (VC Period) and 0 to 4 at Week 8 (LTS Period).
• Participants with percentage 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.

You may not qualify if:

• 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:
• half-lives or 12 weeks, whichever is longer - biologic agents (e.g. dupilumab).
• weeks - systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (e.g. mycophenolate or tacrolimus).
• weeks - immunizations and sedating antihistamines, unless on long-term stable regimen (nonsedating antihistamines are permitted).
• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (66)

University Of Alabama At Birmingham

Birmingham, Alabama, 35233, United States

Location

Center For Dermatology Cosmetic And Laser Surgery

Fremont, California, 94538, United States

Location

Marvel Clinical Research - Clinedge - PPDS

Huntington Beach, California, 92647, United States

Location

Allergy And Asthma Associates Of Southern California - CRN

Mission Viejo, California, 92691, United States

Location

Synexus Clinical Research US Inc. Santa Rosa

Santa Rosa, California, 95405, United States

Location

Olympian Clinical Research

Largo, Florida, 33770, United States

Location

San Marcus Research Clinic Inc

Miami Lakes, Florida, 33014, United States

Location

Well Pharma Medical Research Corporation

South Miami, Florida, 33143, United States

Location

Forward Clinical Trials Inc

Tampa, Florida, 33624, United States

Location

Clinical Research Atlanta - ERN - PPDS

Stockbridge, Georgia, 30281, United States

Location

Northwest Clinical Trials Clinedge

Boise, Idaho, 83704, United States

Location

Randall Dermatology

West Lafayette, Indiana, 47906, United States

Location

Derm Research LLC

Louisville, Kentucky, 40217, United States

Location

Dermatology Specialists PSC

Louisville, Kentucky, 40241, United States

Location

Michael W Simon MD Office

Nicholasville, Kentucky, 40356, United States

Location

Delricht Clinical Research - Clinedge - PPDS Baton Rouge

Baton Rouge, Louisiana, 70809, United States

Location

Hamzavi Dermatology

Fort Gratiot, Michigan, 48059, United States

Location

Jubilee Clinical Research - BTC - PPDS

Las Vegas, Nevada, 89106, United States

Location

ActivMed Practices & Research Inc

Portsmouth, New Hampshire, 03801, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Skin Laser and Surgery specialists of New York and New Jersey LLC

Hackensack, New Jersey, 07601, United States

Location

Derm Research Center Of New York Inc

Stony Brook, New York, 11790, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27516, United States

Location

Synexus Clinical Research US, Inc. - Cincinnati

Cincinnati, Ohio, 45236, United States

Location

Ohio Pediatric Research Association

Dayton, Ohio, 45414, United States

Location

Synexus Clinical Research US, Inc. - Anderson

Anderson, South Carolina, 29621, United States

Location

International Clinical Research Tennessee LLC

Murfreesboro, Tennessee, 37130, United States

Location

Epiphany Dermatology Fort Worth

Fort Worth, Texas, 76244, United States

Location

Dermatology Clinical Research Center of San Antonio

San Antonio, Texas, 78229, United States

Location

Center for Clinical Studies

Webster, Texas, 77598, United States

Location

Tanner Clinic

Layton, Utah, 84041, United States

Location

Advanced Research Institute

Ogden, Utah, 84405, United States

Location

PI Coor Clinical Research LLC

Burke, Virginia, 22015, United States

Location

Clinical Research Partners LLC

Richmond, Virginia, 23220, United States

Location

Dermatology Specialists of Spokane

Spokane, Washington, 99202, United States

Location

Medical Center Unimed EOOD

Sevlievo, Gabrovo, 5400, Bulgaria

Location

Medical Center Excelsior OOD - PPDS

Sofia, 1421, Bulgaria

Location

Diagnostic Consultative Center XXVIII - Sofia - EOOD

Sofia, 1592, Bulgaria

Location

Synexus - Medical Center Synexus Sofia EOOD

Sofia, 1784, Bulgaria

Location

Synexus - Medical Centre Synexus Sofia EOOD (branch - Stara Zagora)

Stara Zagora, 6000, Bulgaria

Location

Wiseman Dermatology Research Inc.

Winnipeg, Manitoba, R3M 3Z4, Canada

Location

The Centre For Clinical Trials Inc.

Oakville, L617W5, Canada

Location

Dermatology Ottawa Research Centre

Ottawa, K2C 3N2, Canada

Location

Dermamedica, s.r.o. - Kozni Ambulance Nachod

Náchod, 547 01, Czechia

Location

CTCenter MaVe s.r.o.

Olomouc, 779 00, Czechia

Location

CCR Ostrava, s.r.o.

Ostrava, 702 00, Czechia

Location

Synexus Affiliate - CLINTRIAL s.r.o.

Prague, 100 00, Czechia

Location

Synexus Czech s.r.o.

Prague, 120 00, Czechia

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Hautarztpraxis Mahlow

Brandenburg, 15831, Germany

Location

Universitatsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Centrum Medyczne Matusiak

Wroclaw, Lower Silesian Voivodeship, 50-566, Poland

Location

Synexus Affiliate - Bialystok - ClinicMed Daniluk, Nowak Spółka Jawna

Bialystok, 15-879, Poland

Location

Centrum Badan Klinicznych PI-House sp. z o.o.

Gdansk, 80-546, Poland

Location

Synexus - Gdynia

Gdynia, 81-537, Poland

Location

Centrum Medyczne Angelius Provita

Katowice, 40-611, Poland

Location

Synexus Affiliate - Krakowskie Centrum Medyczne

Krakow, 31-501, Poland

Location

Twoja Przychodnia - Szczecińskie Centrum Medyczne

Szczecin, 71-434, Poland

Location

Synexus - Warsaw

Warsaw, 01-192, Poland

Location

EMC Instytut Medyczny S.A.

Wroclaw, 50-220, Poland

Location

Wro Medica

Wroclaw, 51-685, Poland

Location

Hospital de Manises

Manises, Valencia, 46940, Spain

Location

Hospital General Universitario de Alicante

Alicante, 3010, Spain

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital General Universitario Reina Sofia

Córdoba, 14001, Spain

Location

Hospital Universitario La Paz - PPDS

Madrid, 28046, Spain

Location

Related Publications (9)

• Simpson EL, Augustin M, Thaci D, Misery L, Armstrong AW, Blauvelt A, Papp KA, Szepietowski JC, Boguniewicz M, Kwatra SG, Kallender H, Sturm D, Ren H, Kircik L. Ruxolitinib Cream Monotherapy Improved Symptoms and Quality of Life in Adults and Adolescents with Mild-to-Moderate Atopic Dermatitis: Patient-Reported Outcomes from Two Phase III Studies. Am J Clin Dermatol. 2025 Jan;26(1):121-137. doi: 10.1007/s40257-024-00901-z. Epub 2024 Nov 15.

  PMID: 39546129 DERIVED

• Blauvelt A, Kallender H, Sturm D, Li Q, Ren H, Eichenfield LF. Efficacy and Safety of Ruxolitinib Cream in Atopic Dermatitis Based on Previous Medication History. Dermatol Ther (Heidelb). 2024 Nov;14(11):3161-3174. doi: 10.1007/s13555-024-01272-3. Epub 2024 Oct 7.

  PMID: 39375281 DERIVED

• Simpson EL, Kircik L, Blauvelt A, Kallender H, Sturm D, Wang M, Eichenfield LF. Ruxolitinib Cream in Adolescents/Adults with Atopic Dermatitis Meeting Severity Thresholds for Systemic Therapy: Exploratory Analysis of Pooled Results from Two Phase 3 Studies. Dermatol Ther (Heidelb). 2024 Aug;14(8):2139-2151. doi: 10.1007/s13555-024-01219-8. Epub 2024 Jul 12.

  PMID: 38995504 DERIVED

• Eichenfield LF, Simpson EL, Papp K, Szepietowski JC, Blauvelt A, Kircik L, Silverberg JI, Siegfried EC, Kuligowski ME, Venturanza ME, Kallender H, Ren H, Paller AS. Efficacy, Safety, and Long-Term Disease Control of Ruxolitinib Cream Among Adolescents with Atopic Dermatitis: Pooled Results from Two Randomized Phase 3 Studies. Am J Clin Dermatol. 2024 Jul;25(4):669-683. doi: 10.1007/s40257-024-00855-2. Epub 2024 May 2.

  PMID: 38698175 DERIVED

• Papp K, Szepietowski JC, Kircik L, Toth D, Eichenfield LF, Forman SB, Kuligowski ME, Kallender H, Sun K, Ren H, Simpson EL. Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies. J Am Acad Dermatol. 2023 May;88(5):1008-1016. doi: 10.1016/j.jaad.2022.09.060. Epub 2022 Nov 26.

  PMID: 36574595 DERIVED

• 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.

  PMID: 36264430 DERIVED

• 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.

  PMID: 33982267 DERIVED

• 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.

  PMID: 33957195 DERIVED

• 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.

  PMID: 33658996 DERIVED

Related Links

• Plain Language Summary of Results

MeSH Terms

Conditions

Dermatitis, Atopic; Pruritus; Eczema

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Michael E. Kuligowski, MD, PhD, MBA

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: November 19, 2018
• Study Start: December 20, 2018
• Primary Completion: November 18, 2019
• Study Completion: November 9, 2020
• Last Updated: September 28, 2023
• Results First Posted: December 17, 2021

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); US (35); DE (3); ES (5); BU (5); PL (10); CZ (5)