Clinical trial NCT06238817: A Study to Evaluate the Efficacy, and Safety Study of Ruxolitinib Cream in Adults With Moderate Atopic Dermatitis
Official title: A Phase 3b, Double-Blind, Multicenter, Randomized, Vehicle-Controlled, Efficacy, and Safety Study of Ruxolitinib Cream in Adults With Moderate Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Atopic Dermatitis
Keywords: Atopic dermatitis
pruritus
eczema
topical therapy
JAK inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2024-02-02
Enrollment: 241
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is being conducted to establish the efficacy of ruxolitinib cream in participants with moderate AD who had an inadequate response to, or are intolerant to, or contraindicated to topical corticosteroid (TCS)s and topical calcineurin inhibitor (TCI)s.


Eligibility criteria: Inclusion Criteria:

* Adults aged ≥ 18 years at screening (Note: Legal adult age for Korea is ≥ 19 years).
* Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria.
* AD duration of at least 2 years.
* IGA score of 3 at screening and Day 1.
* EASI score \> 7 at screening and Day 1.
* Itch NRS score ≥ 4 at Day 1, defined as the average of the 7 days directly before Day 1, with Itch NRS values available for at least 4 of the 7 days.
* %BSA (excluding the scalp) with AD involvement of at least 10% and up to 20% at screening and Day 1.
* DLQI score \> 10 at screening and Day 1.
* Documented recent history (within 12 months before the screening visit) of inadequate response, intolerance, or contraindication to TCSs and TCIs.
* Agree to discontinue all agents used to treat AD from screening through the final follow up visit, except as outlined in the protocol.
* Willingness to avoid pregnancy or fathering children based on the criteria as outlined in the protocol.

Exclusion Criteria:

* Unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator in the 4 weeks prior to Day 1.
* Concurrent conditions and history of other diseases as follows:

  * Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, Wiskott-Aldrich syndrome).
  * Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before Day 1.
  * Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chickenpox) within 1 week before Day 1.
  * Any other concomitant skin disorder (eg, generalized erythroderma, such as Netherton syndrome), 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 classic areas of involvement such as the face or the flexural folds.
  * Other types of eczema within the 6 months prior to screening. Note: Seborrheic dermatitis on the scalp is allowed, as the scalp will not be treated with study cream.
  * Current or history of hepatitis B or C virus infection.
* 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 cream and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
* Any of the following clinical laboratory test results at screening:

  * Hemoglobin \< 10 g/dL.
  * Liver function tests:

    * AST or ALT ≥ 2 × ULN.
    * Alkaline phosphatase \> 1.5 × ULN.
    * Bilirubin \> 1.5 × ULN (isolated bilirubin \> 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%) with the exception of Gilbert's disease.
  * Estimated glomerular filtration rate \< 30 mL/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology Collaboration equation).
  * Positive serology test results for HIV antibody.
  * Any other clinically significant laboratory result that, in the opinion of the investigator, poses a significant risk to the participant.
* Use of any of the following treatments within the indicated washout period before Day 1:

  * 5 half-lives or 12 weeks, whichever is longer: biologic agents. For biologic agents with washout periods longer than 12 weeks (eg, rituximab), consult the medical monitor.
  * 4 weeks: systemic corticosteroids or adrenocorticotropic hormone analogs, cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive (eg, JAK inhibitors) or immunomodulating agents (eg, mycophenolate or tacrolimus).
  * 2 weeks or 5 half-lives, whichever is longer - strong systemic CYP3A4 inhibitors.
  * 2 weeks: immunizations with live-attenuated vaccines; sedating antihistamines unless on a long-term stable regimen (nonsedating antihistamines are permitted).

Note: COVID-19 vaccination is allowed.

• 1 week: use of other topical treatments for AD, other than bland emollients (eg, Aveeno creams, ointments, sprays, soap substitutes), such as antipruritics (eg, doxepin cream), corticosteroids, calcineurin inhibitors, PDE4 inhibitors, coal tar (shampoo), 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 and their frequency remains the same throughout the study.

* History of treatment failure with any systemic or topical JAK inhibitor (eg, ruxolitinib, tofacitinib, baricitinib, abrocitinib, upadacitinib) for AD or any other inflammatory condition.
* 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 that is thought by the investigator to potentially impact the participant's AD.
* 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.
* In the opinion of the investigator, are unable or unlikely to comply with the administration schedule, study evaluations, and procedures (eg, eDiary compliance).

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Primary outcomes:
measure: VC Period: Proportion of participants who achieved Eczema Area and Severity Index 75 (EASI75)
timeFrame: Baseline to Week 8
measure: VC Period: Proportion of participants who achieved Investigator's Global Assessment Treatment Success (IGA-TS)
timeFrame: Baseline to Week 8
Secondary outcomes:
measure: VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)
timeFrame: Baseline to Week 8
measure: VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)
timeFrame: Baseline to Day 7
measure: VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)
timeFrame: Baseline to Day 3
measure: VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)
timeFrame: Baseline to Day 2
measure: VC Period: Number of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Week 24, followed by 30 days follow-up
measure: VC Period: Proportion of participants who achieved Eczema Area and Severity Index 75 (EASI75)
timeFrame: Baseline to Weeks 2 and 4
measure: VC Period: Proportion of participants who achieved Investigator's Global Assessment - Treatment Success (IGA-TS)
timeFrame: Baseline to Weeks 2 and 4
measure: VC Period: Proportion of participants with a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)
timeFrame: Baseline to Weeks 2 and 4
measure: VC Period: Time to achieve a ≥ 4-point improvement in Itch Numeric Rating Scale (NRS) score (ITCH4)
timeFrame: Baseline to Week 8
measure: VC Period: Time to achieve ≥ 2-point improvement from in Itch Numeric Rating Scale (NRS) score (ITCH2)
timeFrame: Baseline to Week 8
measure: VC Period: Change from baseline (pre-study cream application) in current Itch NRS score at 5, 15, 30, 45, and 60 minutes and 2, 4, and 6 hours post-initial dose on Day 1.
timeFrame: Baseline to Day 1
measure: VC Period: Proportion of participants achieving at least a 2-point decrease from baseline in current Itch NRS score at 5, 15, 30, 45, and 60 minutes and 2, 4, and 6 hours post-initial dose on Day 1.
timeFrame: Baseline to Day 1
measure: VC Period: Proportion of participants achieving at least a 4-point decrease from baseline in current Itch NRS score at 5, 15, 30, 45, and 60 minutes and 2, 4, and 6 hours post-initial dose on Day 1.
timeFrame: Baseline to Day 1
measure: VC and VCE Periods: Proportion of participants who achieved EASI50
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Proportion of participants who achieved EASI90
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Proportion of participants achieving both EASI75 and IGA-TS
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change from Baseline in Atopic Dermatitis Afflicted Percentage of Body Surface Area (%BSA)
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change from baseline in EASI score
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change from baseline in SCORAD score
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change from baseline in Itch NRS score
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change from baseline in Skin Pain NRS score
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VCE Period: Time to open-label escape arm
timeFrame: Baseline to Week 24
measure: VC and VCE Periods: Proportion of participants concurrently meeting all of the following criteria: IGA score ≥ 3, EASI score ≥ 16, Itch NRS score ≥ 4, BSA ≥ 10%, and DLQI score > 10
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Time to concurrently meeting all of the following criteria: IGA score ≥ 3, EASI score ≥ 16, Itch NRS score ≥ 4, BSA ≥ 10%, and DLQI score > 10
timeFrame: Baseline to Week 24
measure: VC Period: Proportion of participants who experience a relapse after study treatment discontinuation
timeFrame: Week 24 to Follow-up (30 days)
measure: VCE period: Time to first re-treatment
timeFrame: Week 8 to Week 24
measure: VCE Period: Proportion of time off study treatment due to lesion clearance
timeFrame: Week 8 to Week 24
measure: VCE period: Proportion of time on study treatment
timeFrame: Week 8 to Week 24
measure: VC and VCE Periods: Proportion of participants who achieve ≥ 4-point improvement in DLQI from baseline
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change From Baseline in Dermatology Life Quality Index (DLQI) Score
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change From Baseline in Patient-Oriented Eczema Measure (POEM) Score
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change From Baseline in EuroQuality of Life Five Dimensions (EQ-5D-5L) Visual Analogue Scale (VAS) Score
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change from baseline in the HADS scores
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change from baseline in PROMIS Short Form - Sleep-Related Impairment (8a) 24-Hour Recall Score
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Period: Change From Baseline in PROMIS Short Form - Sleep Disturbance (8b) 7-Day Recall Score
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 20 and 24
measure: VC and VCE Periods: Change from baseline score in Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD)
timeFrame: Baseline to Week 8 and Week 24
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Lynn Institute of the Ozarks
state: Arkansas
city: Fountain Valley
country: United States
facility: First Oc Dermatology
state: California
city: Fremont
country: United States
facility: Center For Dermatology Cosmetic and Laser Surgery
state: California
city: San Diego
country: United States
facility: Medderm Associates, Inc
state: California
city: Hollywood
country: United States
facility: Encore Medical Research, Llc Hollywood
state: Florida
city: Miami
country: United States
facility: Entrust Clinical Research
state: Florida
city: Columbus
country: United States
facility: Lane Dermatology and Dermatologic Surgery
state: Georgia
city: Marietta
country: United States
facility: Marietta Dermatology the Skin Cancer Center Marietta
state: Georgia
city: Rolling Meadows
country: United States
facility: Arlington Dermatology
state: Illinois
city: Skokie
country: United States
facility: Northshore University Healthsystem
state: Illinois
city: Auburn Hills
country: United States
facility: Oakland Hills Dermatology Pc
state: Michigan
city: Troy
country: United States
facility: Revival Research Institute, Llc Troy
state: Michigan
city: Camp Hill
country: United States
facility: Best Skin Research
state: Pennsylvania
city: Murfreesboro
country: United States
facility: International Clinical Research Tennessee Llc
state: Tennessee
city: Houston
country: United States
facility: Center For Clinical Studies Webster
state: Texas
city: Plano
country: United States
facility: Texas Dermatology Research Center
state: Texas
city: San Antonio
country: United States
facility: Rainey and Finklea Dermatology
state: Texas
city: Mill Creek
country: United States
facility: North Sound Dermatology
state: Washington
city: Kogarah
country: Australia
facility: Premier Specialists Pty Ltd
state: New South Wales
city: Maroubra
country: Australia
facility: Australian Clinical Research Network
state: New South Wales
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research
state: Queensland
city: Campbelltown
country: Australia
facility: Clinical Trials Sa
state: South Australia
city: Carlton
country: Australia
facility: Skin Health Institute Inc.
state: Victoria
city: Phillip
country: Australia
facility: Paratus Clinical Research, Woden
city: Brussels
country: Belgium
facility: Cliniques Universitaires Ucl Saint-Luc
city: Bruxelles
country: Belgium
facility: Ulb Hospital Erasme
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (Uza)
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent (Uz Gent)
city: Gilly
country: Belgium
facility: Grand Hopital de Charleroi
city: Kortrijk
country: Belgium
facility: Dermatologie Handelskaai
city: Gabrovo
country: Bulgaria
facility: Mhat Dr. Tota Venkova Ad
city: Pleven
country: Bulgaria
facility: Medical Center Medconsult Pleven Ood
city: Sofia
country: Bulgaria
facility: Ambulatory For Specialized Medical Help - Skin and Venereal Diseases
city: Sofia
country: Bulgaria
facility: Dcc 'Alexandrovska', Eood
city: Sofia
country: Bulgaria
facility: Medical Center Hera Eood
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center Xxviii
city: Sofia
country: Bulgaria
facility: Medical Center Assoc. Prof. Vasilev
city: Calgary
country: Canada
facility: Dermatology Research Institute Inc.
state: Alberta
city: Surrey
country: Canada
facility: Dr. Chih-Ho Hong Medical Inc.
state: British Columbia
city: Winnipeg
country: Canada
facility: Wiseman Dermatology Research Inc
state: Manitoba
city: Fredericton
country: Canada
facility: Dr. Irina Turchin Pc Inc.
state: New Brunswick
city: Markham
country: Canada
facility: Lynderm Research Inc
state: Ontario
city: Peterborough
country: Canada
facility: Skin Centre For Dermatology
state: Ontario
city: Quebec
country: Canada
facility: Centre de Recherche Dermatologique Du Quebec Metropolitain
city: St. John's
country: Canada
facility: Skincare Studio Dermatology Centre
city: Lille Cedex
country: France
facility: Ghicl - Hôpital Saint-Vincent de Paul
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
city: Pierre Bénite Cedex
country: France
facility: Hospices Civils de Lyon Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: Chu de Rouen - Hospital Charles Nicolle
city: Saint Etienne Cedex 2
country: France
facility: University Hospital of Saint Etienne
city: Augsburg
country: Germany
facility: Universitaetsklinikum Augsburg Sued
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim Dermatologie
city: Berlin
country: Germany
facility: Praxis Fuer Haut- Und Geschlechtskrankheiten Dr. Med. Thomas Wildfeuer Und Partner
city: Muenster
country: Germany
facility: Universitatsklinikum Munster
city: Potsdam
country: Germany
facility: Dermatologie Potsdam Mvz Gmbh
city: Budapest
country: Hungary
facility: Clinexpert Kft.
city: Budapest
country: Hungary
facility: Obudai Egeszsegugyi Centrum Kft.
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpon Belgyogy Klinika
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Aok Szent-Gyorgyi Albert Klinikai Kozpont
city: Milano
country: Italy
facility: Fondazione Irccs Ca Granda Ospedale Maggiore
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico Ii
city: Napoli
country: Italy
facility: Universita Degli Studi Della Campania Luigi Vanvitelli
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli Irccs
city: Rozzano
country: Italy
facility: Irccs Istituto Clinico Humanitas
city: Bergen Op Zoom
country: Netherlands
facility: Bravis Ziekenhuis
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis, Molengracht
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych Pi-House Sp. Z O.O.
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia Katowice
city: Krakow
country: Poland
facility: Centrum Medyczne All-Med
city: Kraków
country: Poland
facility: Pratia McM Krakow
city: Lodz
country: Poland
facility: Santa Sp. Z O.O. Santa Familia Ptg Lodz
city: Lublin
country: Poland
facility: Etg Lublin
city: Poznan
country: Poland
facility: Solumed Centrum Medyczne
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecinskie Centrum Medyczne
city: Warszawa
country: Poland
facility: Centrum Medyczne Evimed
city: Warszawa
country: Poland
facility: Klinika Ambroziak Dermatologia
city: Wrocław
country: Poland
facility: Dermmedica Sp. Z O.O.
city: Badalona
country: Spain
facility: Ceim Hospital Universitari Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Madrid
country: Spain
facility: Hospital Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario de La Paz
city: Manises
country: Spain
facility: Hospital de Manises
city: Villajoyosa
country: Spain
facility: Hospital Marina Baixa
city: Basel
country: Switzerland
facility: Universitatsspital Basel
city: Bern
country: Switzerland
facility: Inselspital Universitatsklinik Fur Medizinische Onkologie
city: Buochs
country: Switzerland
facility: Dermatology & Skin Care Clinic
city: Zuerich
country: Switzerland
facility: Universitatsspital Zurich
city: Isleworth
country: United Kingdom
facility: West Middlesex University Hospital
city: London
country: United Kingdom
facility: Guys Hospital
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
city: Plymouth
country: United Kingdom
facility: University Hospital Plymouth
city: Walsall
country: United Kingdom
facility: Walsall Manor Hospital
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: