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

Atopic Dermatitis Clinical Trial

Official title:

A Phase 2, Randomized, Dose-Ranging, Vehicle-Controlled and Triamcinolone 0.1% Cream-Controlled Study to Evaluate the Safety and Efficacy of INCB018424 Phosphate Cream Applied Topically to Adults With Atopic Dermatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03011892
• Other study ID #: INCB 18424-206
• Status: Completed
• Phase: Phase 2
• Start date: January 9, 2017
• Est. completion date: March 12, 2018

Study information

• Verified date: March 2021
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 307
• Est. completion date: March 12, 2018
• Est. primary completion date: January 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Ruxolitinib 0.15% Cream QD
Ruxolitinib 0.15% cream QD
• Ruxolitinib 0.5% Cream QD
Ruxolitinib 0.5% cream QD
• Ruxolitinib 1.5% Cream QD
Ruxolitinib 1.5% cream QD
• Ruxolitinib 1.5% Cream BID
Ruxolitinib 1.5% cream BID
• Triamcinolone 0.1% Cream BID
Triamcinolone 0.1% cream BID
• Vehicle Cream BID
Vehicle cream BID

Locations

Country	Name	City	State
Canada	CCA MEDICAL RESEARCH, 95 Bayly Street West	Ajax	Ontario
Canada	SIMCODERM MEDICAL AND SURGICAL DERMATOLOGY CENTER, 5 Quarry Ridge Road	Barrie	Ontario
Canada	INSTITUTE FOR SKIN ADVANCEMENT, 4935 40th Avenue Nw	Calgary	Alberta
Canada	LYNDERM RESEARCH INC, 25 Main Street Markham North	Markham	Ontario
Canada	DERMEDGE RESEARCH INC., 333 Lakeshore Road West	Mississauga	Ontario
Canada	NORTH BAY DERMATOLOGY CENTRE, 500 Cassells Street	North Bay	Ontario
Canada	RESEARCH BY ICLS, 1344 Cornwall Road	Oakville	Ontario
Canada	OFFICE OF DR. MICHAEL ROBERN, 1 Centrepointe Drive	Ottawa	Ontario
Canada	SKIN CENTRE FOR DERMATOLOGY, 775 Monaghan Road	Peterborough	Ontario
Canada	YORK DERMATOLOGY CENTER, 250 Harding Blvd West	Richmond Hill	Ontario
Canada	CLINIQUE DERMATOLOGIQUE DE SAINT-JEROME, 555 Boul. Saint-antoine	Saint-jerome	Quebec
Canada	DR. CHIH-HO HONG MEDICAL INC., 15300 105 Avenue	Surrey	British Columbia
Canada	RESEARCH TORONTO, 208 Bloor Street West	Toronto	Ontario
Canada	K. PAPP CLINICAL RESEARCH, 135 Union Street East	Waterloo	Ontario
Canada	WINDSOR CLINICAL RESEARCH INC, 2224 Walker Road	Windsor	Ontario
Canada	XLR8 MEDICAL RESEARCH, 2425 Tecumseh Road East	Windsor	Ontario
Canada	WISEMAN DERMATOLOGY RESEARCH INC, 6 - 1170 Taylor Avenue	Winnipeg	Manitoba
United States	ARLINGTON RESEARCH CENTER, INC, 711 East Lamar Blvd	Arlington	Texas
United States	DERMRESEARCH INC., 8140 North Mopac Expressway	Austin	Texas
United States	HASSMAN RESEARCH INSTITUTE, LLC, 175 Cross Keys Road	Berlin	New Jersey
United States	ACTIVMED PRACTICES & RESEARCH, INC, 138 Conant Street	Beverly	Massachusetts
United States	DERMATOLOGISTS OF GREATER COLUMBUS, 2359 East Main Street	Bexley	Ohio
United States	UAB DERMATOLOGY, 2000 6th Avenue South	Birmingham	Alabama
United States	TUFTS MEDICAL CENTER, 800 Washington Street	Boston	Massachusetts
United States	BURKE PHARMACEUTICAL RESEARCH, 601 W. Commerce	Bryant	Arkansas
United States	CHARLOTTESVILLE DERMATOLOGY, 600 Peter Jefferson Parkway	Charlottesville	Virginia
United States	RAPID MEDICAL RESEARCH, INC, 3619 Park East Drive	Cleveland	Ohio
United States	J&S STUDIES, INC, 1710 Crescent Pointe Pkwy	College Station	Texas
United States	HENRY FORD HOSPITAL, 3031 West Grand Blvd	Detroit	Michigan
United States	ENCINO RESEARCH CENTER, 16133 Ventura Blvd	Encino	California
United States	DERMATOLOGY CONSULTING SERVICES, PLLC, 2444 North Main Street	High Point	North Carolina
United States	CENTER FOR CLINICAL STUDIES (CCS), 1401 Binz	Houston	Texas
United States	SUZANNE BRUCE AND ASSOCIATES, PA, 1900 St. James Place	Houston	Texas
United States	DERMATOLOGY RESEARCH ASSOCIATES,8930 South Sepulveda Blvd	Los Angeles	California
United States	DERMRESEARCH, 1169 Eastern Parkway 2310	Louisville	Kentucky
United States	DS RESEARCH, 3810 Springhurst Blvd	Louisville	Kentucky
United States	DS RESEARCH, 2241 Green Valley Road	New Albany	Indiana
United States	CENTRAL SOONER RESEARCH, 900 North Porter	Norman	Oklahoma
United States	DERMATOLOGY SPECIALISTS, INC, 3629 Vista Way	Oceanside	California
United States	PARISH DERMATOLOGY, INC, 1845 Walnut Street	Philadelphia	Pennsylvania
United States	THE INDIANA CLINICAL TRIALS CENTER, 824 Edwards Drive	Plainfield	Indiana
United States	ACTIVMED PRACTICES AND RESEARCH, INC, 110 Corporate Drive	Portsmouth	New Hampshire
United States	WAKE RESEARCH ASSOCIATES LLC, 3100 Duraleigh Road	Raleigh	North Carolina
United States	INTEGRATED RESEARCH GROUP, INC, 4646 Brockton Avenue	Riverside	California
United States	WASHINGTON UNIVERSITY - DERMATOLOGY, 4921 Parkview Place	Saint Louis	Missouri
United States	WASHINGTON UNIVERSITY - DERMATOLOGY, 969 Mason Road	Saint Louis	Missouri
United States	CLINICAL TRIALS OF TEXAS, INC, 7940 Floyd Curl Drive	San Antonio	Texas
United States	DERMATOLOGY CLINICAL RESEARCH CENTER OF SAN ANTONIO, 7810 Louis Pasteur	San Antonio	Texas
United States	SAN LUIS DERMATOLOGY AND LASER CLINIC, 15 Santa Rosa Street	San Luis Obispo	California
United States	NEW ENGLAND RESEARCH ASSOCIATES LLC, 5520 Park Avenue	Trumbull	Connecticut
United States	PEAK RESEARCH LLC, 2589 Washington Rd	Upper Saint Clair	Pennsylvania
United States	CENTER FOR CLINICAL STUDIES, 451 North Texas Avenue	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 BID	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.	Baseline and Week 4
Secondary	Mean Percentage Change From Baseline in EASI Score at Week 4 in Participants Treated With Ruxolitinib QD Compared With Participants Treated With Vehicle Cream BID	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.	Baseline and Week 4
Secondary	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 Vehicle	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.	Baseline and Week 4
Secondary	Mean Percentage Change From Baseline in EASI Score at Week 2 and Week 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.	Baseline, Week 2 and 8
Secondary	Percentage of Participants Who Achieve a = 50% Improvement From Baseline in EASI (EASI-50) at Weeks 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).	Week 2, 4 and 8
Secondary	Percentage Change From Baseline in EASI Score at 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.	Baseline and Week 4
Secondary	Time to Achieve EASI-50	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.	From Baseline to Week 8
Secondary	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 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.	Week 2, 4 and 8
Secondary	Mean Change From Baseline in the Itch Numerical Rating Scale (NRS) Score at Weeks 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.	Baseline, Week 2, 4 and 8
Secondary	Number of Participants With At Least One Adverse Event (AEs) and as Per Severity	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.	Up to Week 24