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A Study to Evaluate the Safety and Efficacy of Ruxolitinib Phosphate Cream Applied Topically to Adults With Atopic Dermatitis

Registration Number
NCT03011892
Lead Sponsor
Incyte Corporation
Brief Summary

The purpose of this study is to establish the efficacy of each strength of ruxolitinib cream once daily (QD) or twice daily (BID) in participants with atopic dermatitis as compared with vehicle cream BID.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
307
Inclusion Criteria
  • Participants diagnosed with atopic dermatitis (AD) as defined by the Hanifin and Rajka criteria.
  • Participants with a history of AD for at least 2 years.
  • Participants with an Investigator's Global Assessment (IGA) score of 2 to 3 at screening and baseline.
  • Participants with body surface area (BSA) of AD involvement, excluding the face and intertriginous areas, of 3% to 20% at screening and baseline.
  • Participants who agree to discontinue all agents used to treat AD from screening through the final follow-up visit.
Exclusion Criteria
  • Participants with evidence of active acute or chronic infections.

  • Use of topical treatments for AD (other than bland emollients) within 2 weeks of baseline.

  • Systemic immunosuppressive or immunomodulating drugs (eg, oral or injectable corticosteroids, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine) within 4 weeks or 5 half-lives of baseline (whichever is longer).

  • Participants with other dermatologic disease besides AD whose presence or treatments could complicate the assessment of disease (eg, psoriasis).

  • Participants with a history of other diseases besides dermatologic disorders (eg, other autoimmune diseases) taking treatments that could complicate assessments.

  • Participants with cytopenias at screening, defined as:

    • Leukocytes < 3.0 × 10^9/L.
    • Neutrophils < lower limit of normal.
    • Hemoglobin < 10 g/dL.
    • Lymphocytes < 0.8 × 10^9/L
    • Platelets < 100 × 10^9/L.
  • Participants with severely impaired liver function (Child-Pugh Class C) or end-stage renal disease (ESRD) on dialysis or at least 1 of the following:

    • Serum creatinine > 1.5 mg/dL.
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 × upper limit of normal.
  • Participants taking potent systemic cytochrome P450 3A4 inhibitors or fluconazole within 2 weeks or 5 half-lives, whichever is longer, before the baseline visit (topical agents with limited systemic availability are permitted).

  • Participants who have previously received Janus kinase (JAK) inhibitors, systemic or topical (e.g., ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, pacritinib).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DB: Ruxolitinib 1.5% BIDRuxolitinib 1.5% Cream BIDParticipants applied ruxolitinib 1.5% cream BID for 8 weeks in DB period.
DB: Triamcinolone (TAC) 0.1% BID/Vehicle Cream BIDTriamcinolone 0.1% Cream BIDParticipants applied triamcinolone 0.1% cream BID for 4 weeks followed by vehicle cream for 4 weeks in DB period.
DB: Ruxolitinib 0.15% Once Daily (QD)Ruxolitinib 0.15% Cream QDParticipants applied ruxolitinib 0.15% cream QD for 8 weeks in DB period.
Open-Label (OL): Vehicle BID to Ruxolitinib 1.5% BIDRuxolitinib 1.5% Cream BIDFollowing DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
OL: Ruxolitinib 1.5% QD to Ruxolitinib 1.5% BIDRuxolitinib 1.5% Cream BIDFollowing DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
Double Blind (DB): Vehicle BIDVehicle Cream BIDParticipants applied vehicle cream twice daily (BID) for 8 weeks DB period.
OL: TAC BID/Vehicle BID to Ruxolitinib 1.5% BIDRuxolitinib 1.5% Cream BIDFollowing DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
DB: Ruxolitinib 0.5% QDRuxolitinib 0.5% Cream QDParticipants applied ruxolitinib 0.5% cream QD for 8 weeks in DB period.
OL: Ruxolitinib 0.15% QD to Ruxolitinib 1.5% BIDRuxolitinib 1.5% Cream BIDFollowing DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
DB: Ruxolitinib 1.5% QDRuxolitinib 1.5% Cream QDParticipants applied ruxolitinib 1.5% cream QD for 8 weeks in DB period.
DB: Triamcinolone (TAC) 0.1% BID/Vehicle Cream BIDVehicle Cream BIDParticipants applied triamcinolone 0.1% cream BID for 4 weeks followed by vehicle cream for 4 weeks in DB period.
OL: Ruxolitinib 0.5% QD to Ruxolitinib 1.5% BIDRuxolitinib 1.5% Cream BIDFollowing DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
OL: Ruxolitinib 1.5% BID to Ruxolitinib 1.5% BIDRuxolitinib 1.5% Cream BIDFollowing DB Period, at Week 8, participants who met criteria (compliant with the protocol and no safety concerns) received open-label treatment with ruxolitinib 1.5% cream BID for 4 weeks.
Primary Outcome Measures
NameTimeMethod
Mean Percentage Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 4 in Participants Treated With Ruxolitinib 1.5% Cream Twice a Day (BID) Compared With Participants Treated With Vehicle Cream BIDBaseline and Week 4

EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI 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. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement.

Secondary Outcome Measures
NameTimeMethod
Time to Achieve EASI-50From Baseline to Week 8

Time to EASI-50 is defined as the interval between the time of randomization and the time of achieving at least 50% improvement in EASI score.

Percentage Change From Baseline in EASI Score at Week 4Baseline and Week 4

EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI 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. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement.

Mean Percentage Change From Baseline in EASI Score at Week 4 in Participants Treated With Ruxolitinib QD Compared With Participants Treated With Vehicle Cream BIDBaseline and Week 4

EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI 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. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement.

Number of Participants With At Least One Adverse Event (AEs) and as Per SeverityUp to Week 24

AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. The severity of AEs was assessed using CTCAE v4.03 Grades 1 through 4.Data are reported for Grade 3 and higher severity for this outcome measure.

Mean Percentage Change From Baseline in EASI Score at Week 4 in Participants Treated With Ruxolitinib QD/BID Cream Compared With Participants Treated With Triamcinolone 0.1% Cream BID Followed by VehicleBaseline and Week 4

EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI 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. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement.

Percentage of Participants Who Achieve a ≥ 50% Improvement From Baseline in EASI (EASI-50) at Weeks 2, 4, and 8Week 2, 4 and 8

The categorical variable EASI-50 will be equal to 1 for percentage improvement from baseline in EASI score of 50% or greater and will be equal to 0 for percentage improvement of less than 50%. This definition is introduced for the purpose of identifying participants who respond to the treatment (1 = responder, 0 = non-responder).

Mean Percentage Change From Baseline in EASI Score at Week 2 and Week 8Baseline, Week 2 and 8

EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). The EASI score examines 4 areas of the body and weights them for participants 8 years of age and older as follows: Head/Neck (H) = 0.1, Upper limbs (UL) = 0.2, Trunk (T) = 0.3, and Lower limbs (LL) = 0.4. The severity strata for the EASI 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. The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement.

Percentage of Participants Achieving an Investigator's Global Assessment (IGA) Score of 0 to 1 Who Have an Improvement of ≥ 2 Points From Baseline at Weeks 2, 4, and 8Week 2, 4 and 8

IGA is an assessment scale used to determine severity of atopic dermatitis (AD) and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). An IGA responder was defined as a participant achieving an IGA score of 0 to 1 and an IGA score improvement at least 2 from baseline.

Mean Change From Baseline in the Itch Numerical Rating Scale (NRS) Score at Weeks 2, 4, and 8Baseline, Week 2, 4 and 8

The Itch NRS is a once-per-24 hours ("daily") participant-reported measure of itch intensity 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. The categorical NRS is defined as 0 = None, 1 to 3 = Mild, 4 to 6 = Moderate, and 7 to 10 = Severe.

Trial Locations

Locations (52)

HASSMAN RESEARCH INSTITUTE, LLC, 175 Cross Keys Road

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Berlin, New Jersey, United States

ACTIVMED PRACTICES & RESEARCH, INC, 138 Conant Street

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Beverly, Massachusetts, United States

CENTER FOR CLINICAL STUDIES (CCS), 1401 Binz

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Houston, Texas, United States

UAB DERMATOLOGY, 2000 6th Avenue South

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Birmingham, Alabama, United States

ARLINGTON RESEARCH CENTER, INC, 711 East Lamar Blvd

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Arlington, Texas, United States

WASHINGTON UNIVERSITY - DERMATOLOGY, 4921 Parkview Place

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Saint Louis, Missouri, United States

ACTIVMED PRACTICES AND RESEARCH, INC, 110 Corporate Drive

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Portsmouth, New Hampshire, United States

BURKE PHARMACEUTICAL RESEARCH, 601 W. Commerce

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Bryant, Arkansas, United States

HENRY FORD HOSPITAL, 3031 West Grand Blvd

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Detroit, Michigan, United States

DERMATOLOGISTS OF GREATER COLUMBUS, 2359 East Main Street

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Bexley, Ohio, United States

CENTRAL SOONER RESEARCH, 900 North Porter

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Norman, Oklahoma, United States

PEAK RESEARCH LLC, 2589 Washington Rd

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Upper Saint Clair, Pennsylvania, United States

DERMRESEARCH INC., 8140 North Mopac Expressway

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Austin, Texas, United States

WASHINGTON UNIVERSITY - DERMATOLOGY, 969 Mason Road

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Saint Louis, Missouri, United States

CLINICAL TRIALS OF TEXAS, INC, 7940 Floyd Curl Drive

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San Antonio, Texas, United States

TUFTS MEDICAL CENTER, 800 Washington Street

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Boston, Massachusetts, United States

WISEMAN DERMATOLOGY RESEARCH INC, 6 - 1170 Taylor Avenue

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Winnipeg, Manitoba, Canada

CLINIQUE DERMATOLOGIQUE DE SAINT-JEROME, 555 Boul. Saint-antoine

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Saint-jerome, Quebec, Canada

LYNDERM RESEARCH INC, 25 Main Street Markham North

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Markham, Ontario, Canada

DERMATOLOGY CONSULTING SERVICES, PLLC, 2444 North Main Street

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High Point, North Carolina, United States

RAPID MEDICAL RESEARCH, INC, 3619 Park East Drive

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Cleveland, Ohio, United States

WAKE RESEARCH ASSOCIATES LLC, 3100 Duraleigh Road

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Raleigh, North Carolina, United States

CENTER FOR CLINICAL STUDIES, 451 North Texas Avenue

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Webster, Texas, United States

SIMCODERM MEDICAL AND SURGICAL DERMATOLOGY CENTER, 5 Quarry Ridge Road

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Barrie, Ontario, Canada

XLR8 MEDICAL RESEARCH, 2425 Tecumseh Road East

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Windsor, Ontario, Canada

DERMEDGE RESEARCH INC., 333 Lakeshore Road West

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Mississauga, Ontario, Canada

DERMATOLOGY RESEARCH ASSOCIATES,8930 South Sepulveda Blvd

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Los Angeles, California, United States

INTEGRATED RESEARCH GROUP, INC, 4646 Brockton Avenue

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Riverside, California, United States

SAN LUIS DERMATOLOGY AND LASER CLINIC, 15 Santa Rosa Street

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San Luis Obispo, California, United States

NEW ENGLAND RESEARCH ASSOCIATES LLC, 5520 Park Avenue

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Trumbull, Connecticut, United States

THE INDIANA CLINICAL TRIALS CENTER, 824 Edwards Drive

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Plainfield, Indiana, United States

DERMRESEARCH, 1169 Eastern Parkway 2310

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Louisville, Kentucky, United States

DS RESEARCH, 3810 Springhurst Blvd

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Louisville, Kentucky, United States

PARISH DERMATOLOGY, INC, 1845 Walnut Street

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Philadelphia, Pennsylvania, United States

DR. CHIH-HO HONG MEDICAL INC., 15300 105 Avenue

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Surrey, British Columbia, Canada

OFFICE OF DR. MICHAEL ROBERN, 1 Centrepointe Drive

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Ottawa, Ontario, Canada

YORK DERMATOLOGY CENTER, 250 Harding Blvd West

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Richmond Hill, Ontario, Canada

RESEARCH TORONTO, 208 Bloor Street West

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Toronto, Ontario, Canada

WINDSOR CLINICAL RESEARCH INC, 2224 Walker Road

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Windsor, Ontario, Canada

SKIN CENTRE FOR DERMATOLOGY, 775 Monaghan Road

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Peterborough, Ontario, Canada

ENCINO RESEARCH CENTER, 16133 Ventura Blvd

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Encino, California, United States

DERMATOLOGY SPECIALISTS, INC, 3629 Vista Way

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Oceanside, California, United States

DS RESEARCH, 2241 Green Valley Road

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New Albany, Indiana, United States

J&S STUDIES, INC, 1710 Crescent Pointe Pkwy

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College Station, Texas, United States

SUZANNE BRUCE AND ASSOCIATES, PA, 1900 St. James Place

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Houston, Texas, United States

DERMATOLOGY CLINICAL RESEARCH CENTER OF SAN ANTONIO, 7810 Louis Pasteur

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San Antonio, Texas, United States

CHARLOTTESVILLE DERMATOLOGY, 600 Peter Jefferson Parkway

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Charlottesville, Virginia, United States

INSTITUTE FOR SKIN ADVANCEMENT, 4935 40th Avenue Nw

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Calgary, Alberta, Canada

CCA MEDICAL RESEARCH, 95 Bayly Street West

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Ajax, Ontario, Canada

NORTH BAY DERMATOLOGY CENTRE, 500 Cassells Street

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North Bay, Ontario, Canada

RESEARCH BY ICLS, 1344 Cornwall Road

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Oakville, Ontario, Canada

K. PAPP CLINICAL RESEARCH, 135 Union Street East

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Waterloo, Ontario, Canada

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