Clinical trial NCT03745651: TRuE AD2 - An Efficacy and Safety Study of Ruxolitinib Cream in Adolescents and Adults With Atopic Dermatitis
Official title: Topical Ruxolitinib Evaluation in Atopic Dermatitis Study 2 (TRuE AD2) - 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atopic Dermatitis
Keywords: Atopic dermatitis
pruritus
eczema
topical therapy
JAK inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-11-19
Enrollment: 618
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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 (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.

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 (e.g. dupilumab).
  * 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (e.g. 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.

Primary outcomes:
measure: VC Period: Percentage of Participants Who Achieved Investigator's Global Assessment - Treatment Success (IGA-TS) at Week 8
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: VC Period: Percentage of Participants Who Achieved Eczema Area and Severity Index 75 (EASI75) at Week 8
timeFrame: Baseline to Week 8
measure: VC Period: Percentage of Participants With a ≥ 4-Point Improvement in Itch Numerical Rating Scale (NRS) Score From Baseline to Week 8
timeFrame: Baseline to Week 8
measure: 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
timeFrame: Baseline to Week 8
measure: 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
timeFrame: Baseline to Week 8
measure: VC Period: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Treatment-Emergent Serious Adverse Event (SAE)
timeFrame: From date of randomization up to Week 8
measure: LTS Period: Percentage of Participants With at Least One TEAE and Treatment Emergent SAE
timeFrame: From first dose date in LTS Period (Week 8) until last follow-up visit (up to 52 weeks)
measure: VC Period: Percentage of Participants Who Achieved an IGA-TS at Weeks 2 and 4
timeFrame: Baseline to Weeks 2 and 4
measure: VC Period: Percentage of Participants Achieving an IGA of 0 or 1
timeFrame: Weeks 2, 4 and 8
measure: LTS Period: Percentage of Participants Achieving an IGA of 0 or 1
timeFrame: Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52
measure: VC Period: Percentage of Participants With a ≥ 4-Point Improvement in Itch NRS Score From Baseline to Weeks 2 and 4
timeFrame: Baseline to Weeks 2 and 4
measure: VC Period: Percentage of Participants Who Achieved EASI50
timeFrame: Baseline to Weeks 2, 4 and 8
measure: VC Period: Percentage of Participants Who Achieved EASI75 at Weeks 2 and 4
timeFrame: Baseline to Weeks 2 and 4
measure: VC Period: Percentage of Participants Who Achieved EASI90
timeFrame: Baseline to Weeks 2, 4 and 8
measure: VC Period: Percent Change From Baseline in EASI Score
timeFrame: Baseline, Weeks 2, 4 and 8
measure: VC Period: Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score
timeFrame: Baseline, Weeks 2, 4 and 8
measure: VC Period: Change From Baseline in Itch NRS Score
timeFrame: Baseline, Weeks 2, 4 and 8
measure: VC Period: Time to Achieve Itch NRS Score Improvement of at Least 2, 3, or 4 Points
timeFrame: Up to Week 8
measure: VC Period: Change From Baseline in Skin Pain NRS Score
timeFrame: Baseline, Weeks 2, 4 and 8
measure: VC Period: Percentage of Participants With a Clinically Meaningful (≥ 6-Point) Improvement in the PROMIS Short Form - Sleep Disturbance (8b) 24-Hour Recall Score at Weeks 2 and 4
timeFrame: Weeks 2 and 4
measure: 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 Weeks 2 and 4
timeFrame: Weeks 2 and 4
measure: VC Period: Change From Baseline in PROMIS Short Form - Sleep Disturbance (8b) 24-Hour Recall Score
timeFrame: Baseline, Weeks 2, 4 and 8
measure: VC Period: Change From Baseline in PROMIS Short Form - Sleep-Related Impairment (8a) 24-Hour Recall Score
timeFrame: Baseline, Weeks 2, 4 and 8
measure: LTS Period: Change From Baseline in PROMIS Short Form - Sleep-Related Impairment (8a) 7-Day Recall Score
timeFrame: Baseline, Weeks 12, 24, and 52
measure: LTS Period: Change From Baseline in PROMIS Short Form - Sleep Disturbance (8b) 7-Day Recall Score
timeFrame: Baseline, Weeks 12, 24, and 52
measure: VC Period: Change From Baseline in Atopic Dermatitis Afflicted Percentage of Body Surface Area (%BSA)
timeFrame: Baseline, Weeks 2, 4 and 8
measure: LTS Period: Change From Baseline in Atopic Dermatitis Afflicted %BSA
timeFrame: Baseline, Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
measure: VC Period: Change From Baseline in Patient-Oriented Eczema Measure (POEM) Score
timeFrame: Baseline, Weeks 2, 4 and 8
measure: LTS Period: Change From Baseline in POEM Score
timeFrame: Baseline, Weeks 12, 24 and 52
measure: VC Period: Change From Baseline in Dermatology Life Quality Index (DLQI) Score
timeFrame: Baseline, Weeks 2, 4, and 8
measure: LTS Period: Change From Baseline in DLQI Score
timeFrame: Baseline, Weeks 12, 24, and 52
measure: VC Period: Change From Baseline in Children Dermatology Life Quality Index (CDLQI) Score
timeFrame: Baseline, Weeks 2, 4, and 8
measure: LTS Period: Change From Baseline in CDLQI Score
timeFrame: Baseline, Weeks 12, 24, and 52
measure: VC Period: Mean Patient Global Impression of Change (PGIC) Score at Weeks 2, 4, and 8
timeFrame: Weeks 2, 4 and 8
measure: VC Period: Percentage of Participants With Each Score on the PGIC at Weeks 2, 4, and 8
timeFrame: Weeks 2, 4 and 8
measure: VC Period: Percentage of Participants With a Score of Either 1 or 2 on the PGIC at Weeks 2, 4, and 8
timeFrame: Weeks 2, 4 and 8
measure: VC Period: Change From Baseline in EuroQuality of Life Five Dimensions (EQ-5D-5L) Visual Analogue Scale (VAS) Score
timeFrame: Baseline, Weeks 2, 4 and 8
measure: VC Period: Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) Version 2.0 (v2.0)
timeFrame: Baseline, Weeks 2, 4, and 8
measure: LTS Period: Change From Baseline in WPAI-SHP v2.0
timeFrame: Baseline, Weeks 12, 24, 36, and 52
measure: VC Period: Trough Plasma Concentrations of Ruxolitinib
timeFrame: Pre-dose at Weeks 2, 4 and 8
measure: LTS Period: Trough Plasma Concentrations of Ruxolitinib
timeFrame: Pre-dose at Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham
state: Alabama
city: Fremont
country: United States
facility: Center For Dermatology Cosmetic And Laser Surgery
state: California
city: Huntington Beach
country: United States
facility: Marvel Clinical Research - Clinedge - PPDS
state: California
city: Mission Viejo
country: United States
facility: Allergy And Asthma Associates Of Southern California - CRN
state: California
city: Santa Rosa
country: United States
facility: Synexus Clinical Research US Inc. Santa Rosa
state: California
city: Largo
country: United States
facility: Olympian Clinical Research
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic Inc
state: Florida
city: South Miami
country: United States
facility: Well Pharma Medical Research Corporation
state: Florida
city: Tampa
country: United States
facility: Forward Clinical Trials Inc
state: Florida
city: Stockbridge
country: United States
facility: Clinical Research Atlanta - ERN - PPDS
state: Georgia
city: Boise
country: United States
facility: Northwest Clinical Trials Clinedge
state: Idaho
city: West Lafayette
country: United States
facility: Randall Dermatology
state: Indiana
city: Louisville
country: United States
facility: Derm Research LLC
state: Kentucky
city: Louisville
country: United States
facility: Dermatology Specialists PSC
state: Kentucky
city: Nicholasville
country: United States
facility: Michael W Simon MD Office
state: Kentucky
city: Baton Rouge
country: United States
facility: Delricht Clinical Research - Clinedge - PPDS Baton Rouge
state: Louisiana
city: Fort Gratiot
country: United States
facility: Hamzavi Dermatology
state: Michigan
city: Las Vegas
country: United States
facility: Jubilee Clinical Research - BTC - PPDS
state: Nevada
city: Portsmouth
country: United States
facility: ActivMed Practices & Research Inc
state: New Hampshire
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Hackensack
country: United States
facility: Skin Laser and Surgery specialists of New York and New Jersey LLC
state: New Jersey
city: Stony Brook
country: United States
facility: Derm Research Center Of New York Inc
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Synexus Clinical Research US, Inc. - Cincinnati
state: Ohio
city: Dayton
country: United States
facility: Ohio Pediatric Research Association
state: Ohio
city: Anderson
country: United States
facility: Synexus Clinical Research US, Inc. - Anderson
state: South Carolina
city: Murfreesboro
country: United States
facility: International Clinical Research Tennessee LLC
state: Tennessee
city: Fort Worth
country: United States
facility: Epiphany Dermatology Fort Worth
state: Texas
city: San Antonio
country: United States
facility: Dermatology Clinical Research Center of San Antonio
state: Texas
city: Webster
country: United States
facility: Center for Clinical Studies
state: Texas
city: Layton
country: United States
facility: Tanner Clinic
state: Utah
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Burke
country: United States
facility: PI Coor Clinical Research LLC
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners LLC
state: Virginia
city: Spokane
country: United States
facility: Dermatology Specialists of Spokane
state: Washington
city: Sevlievo
country: Bulgaria
facility: Medical Center Unimed EOOD
state: Gabrovo
city: Sofia
country: Bulgaria
facility: Medical Center Excelsior OOD - PPDS
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center XXVIII - Sofia - EOOD
city: Sofia
country: Bulgaria
facility: Synexus - Medical Center Synexus Sofia EOOD
city: Stara Zagora
country: Bulgaria
facility: Synexus - Medical Centre Synexus Sofia EOOD (branch - Stara Zagora)
city: Winnipeg
country: Canada
facility: Wiseman Dermatology Research Inc.
state: Manitoba
city: Oakville
country: Canada
facility: The Centre For Clinical Trials Inc.
city: Ottawa
country: Canada
facility: Dermatology Ottawa Research Centre
city: Nachod
country: Czechia
facility: Dermamedica, s.r.o. - Kozni Ambulance Nachod
city: Olomouc
country: Czechia
facility: CTCenter MaVe s.r.o.
city: Ostrava
country: Czechia
facility: CCR Ostrava, s.r.o.
city: Prague 2
country: Czechia
facility: Synexus Czech s.r.o.
city: Praha
country: Czechia
facility: Synexus Affiliate - CLINTRIAL s.r.o.
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Brandenburg
country: Germany
facility: Hautarztpraxis Mahlow
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: Wroclaw
country: Poland
facility: Centrum Medyczne Matusiak
state: Dolnoslaskie
city: Bialystok
country: Poland
facility: Synexus Affiliate - Bialystok - ClinicMed Daniluk, Nowak Spółka Jawna
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI-House sp. z o.o.
city: Gdynia
country: Poland
facility: Synexus - Gdynia
city: Katowice
country: Poland
facility: Centrum Medyczne Angelius Provita
city: Krakow
country: Poland
facility: Synexus Affiliate - Krakowskie Centrum Medyczne
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecińskie Centrum Medyczne
city: Warszawa
country: Poland
facility: Synexus - Warsaw
city: Wroclaw
country: Poland
facility: EMC Instytut Medyczny S.A.
city: Wroclaw
country: Poland
facility: Wro Medica
city: Manises
country: Spain
facility: Hospital de Manises
state: Valencia
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Cordoba
country: Spain
facility: Hospital General Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
Study officials:
affiliation: Incyte Corporation
name: Michael E. Kuligowski, MD, PhD, MBA
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.