Clinical trial NCT03745638: Topical Ruxolitinib Evaluation in Atopic Dermatitis Study 1 (TRuE AD1) - An Efficacy and Safety Study of Ruxolitinib Cream in Adolescents and Adults With Atopic Dermatitis
Official title: 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: 631
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 and safety of twice daily 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 \[Vehicle Controlled (VC) Period\] and 0 to 4 at Week 8 \[Long-Term Safety (LTS) Period\].
* Participants with percentage of 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 (eg. dupilumab).
  * 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporin, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg. 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: 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)
timeFrame: Baseline to Week 8
measure: VC Period: Percentage of Participants With a ≥ 4-Point Improvement in Itch Numerical Rating Scale (NRS) Score
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
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)
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 first dose 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 IGA Scores of 0 or 1
timeFrame: Weeks 2, 4 and 8
measure: LTS Period: Percentage of Participants Achieving IGA Scores 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 Achieving EASI50
timeFrame: Weeks 2, 4 and 8
measure: VC Period: Percentage of Participants Achieving EASI75
timeFrame: Weeks 2 and 4
measure: VC Period: Percentage of Participants Achieving EASI90
timeFrame: 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
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
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: Cahaba Dermatology
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies
state: Arizona
city: Fountain Valley
country: United States
facility: First OC Dermatology
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: Oceanside
country: United States
facility: Dermatology Specialists Inc
state: California
city: Riverside
country: United States
facility: Integrated Research Group Inc.
state: California
city: Westminster
country: United States
facility: Advanced Rx Clinical Research
state: California
city: Boca Raton
country: United States
facility: Clearlyderm Boca Raton - BTC - PPDS
state: Florida
city: Largo
country: United States
facility: Olympian Clinical Research
state: Florida
city: Miami
country: United States
facility: Acevedo Clinical Research
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research Corporation
state: Florida
city: Miami
country: United States
facility: AdvancedPharma CR LLC
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute Inc
state: Florida
city: Savannah
country: United States
facility: Aeroallergy Research Lab Of Savannah
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta - ERN-PPDS
state: Georgia
city: Normal
country: United States
facility: Sneeze Wheeze and Itch Associates LLC
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group LLC
state: Indiana
city: New Albany
country: United States
facility: DS Research
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Dermatology P.A.
state: Kansas
city: Louisville
country: United States
facility: Skin Sciences, PLLC
state: Kentucky
city: Nicholasville
country: United States
facility: Michael W Simon MD
state: Kentucky
city: Rockville
country: United States
facility: DermAssociates
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: Las Vegas
country: United States
facility: JDR Dermatology Research
state: Nevada
city: Forest Hills
country: United States
facility: Forest Hills Dermatology Group
state: New York
city: New York
country: United States
facility: Sadick Dermatology
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Huber Heights
country: United States
facility: Ohio Pediatric Research Assn Inc
state: Ohio
city: Norman
country: United States
facility: Central Sooner Research
state: Oklahoma
city: Gresham
country: United States
facility: Cyn3rgy Research - Clinedge - PPDS
state: Oregon
city: Medford
country: United States
facility: Clinical Research Institute Of Southern Oregon - Crisor
state: Oregon
city: Portland
country: United States
facility: Oregon Medical Research Center PC
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Greer
country: United States
facility: Synexus Clinical Research Us Inc. Greer
state: South Carolina
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Tennessee
city: Carrollton
country: United States
facility: Family Medicine Associates Of Texas
state: Texas
city: San Antonio
country: United States
facility: Progressive Clinical Research PA
state: Texas
city: West Jordan
country: United States
facility: Jordan Valley Medical Center
state: Utah
city: Burke
country: United States
facility: PI Coor Clinical Research LLC
state: Virginia
city: Henrico
country: United States
facility: West End Dermatology
state: Virginia
city: Markham
country: Canada
facility: Lynderm Research Inc
state: Ontario
city: Richmond Hill
country: Canada
facility: York Dermatology Center
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research
state: Ontario
city: Windsor
country: Canada
facility: Windsor Clinical Research Inc.
state: Ontario
city: Windsor
country: Canada
facility: XLR8 Medical Research
state: Ontario
city: Westmount
country: Canada
facility: Siena Medical Reserch Corporation
state: Quebec
city: Brest
country: France
facility: CHRU de Brest - Hopital Morvan
city: Martigues
country: France
facility: Le Bateau Blanc - Imm. A
city: Nice
country: France
facility: Hôpital L'archet 2
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Buxtehude
country: Germany
facility: Elben Klinken Stade - Buxtehude
state: Niedersachsen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden
state: Sachsen
city: Lübeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Budapest
country: Hungary
facility: Synexus (DRS) - Synexus Magyarország Kft. Budapest
city: Debrecen
country: Hungary
facility: Synexus Affiliate - Synexus Magyarorszag Kft. Debrecen
city: Gyula
country: Hungary
facility: Synexus (DRS) - Synexus Magyarország Kft. Gyula
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem
city: Szolnok
country: Hungary
facility: Allergo-Derm Bakos Kft.
city: Zalaegerszeg
country: Hungary
facility: Synexus (DRS) - Synexus Magyarország Kft. Zalaegerszeg
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
city: Wroclaw
country: Poland
facility: Synexus - Wroclaw
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Centrum Medyczne ADAMAR
state: Dolnoslaskie
city: Zgierz
country: Poland
facility: ETG Zgierz
state: Lódzkie
city: Warsaw
country: Poland
facility: Klinika Ambroziak
state: Mazowieckie
city: Gdansk
country: Poland
facility: Synexus - Gdansk
state: Pomorskie
city: Szczecin
country: Poland
facility: Laser Clinic S.C.
state: Zachodniopomorskie
city: Katowice
country: Poland
facility: Synexus - Katowice
city: Krakow
country: Poland
facility: Centrum Medyczne Krakow - PRATIA - PPDS
city: Lublin
country: Poland
facility: ETG Lublin
city: Poznan
country: Poland
facility: Synexus Polska Sp. z o.o. Oddzial w Poznaniu
city: Tarnow
country: Poland
facility: Alergo-Med Specjalistyczna Przychodnia Lekarska Sp. z.o.o
city: Warsaw
country: Poland
facility: ETG Warszawa
city: Warszawa
country: Poland
facility: Medycyna Kliniczna Marzena Waszczak-Jeka
city: Warszawa
country: Poland
facility: Royalderm
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.