TRuE AD2 - An Efficacy and Safety Study of Ruxolitinib Cream in Adolescents and Adults With Atopic Dermatitis

• ClinicalTrials.gov Identifier: NCT03745651
• Recruitment Status: Completed
• First Posted: November 19, 2018
• Last Update Posted: November 19, 2020
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: November 15, 2018
• First Posted Date: November 19, 2018
• Last Update Posted Date: November 19, 2020
• Actual Study Start Date: December 20, 2018
• Actual Primary Completion Date: November 18, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 15, 2018)

Proportion of participants achieving Investigator's Global Assessment Treatment Success (IGA-TS) [ Time Frame: From baseline up to 8 weeks ]

Defined as Investigator's Global Assessment (IGA) score of 0 or 1 with ≥ 2 grade improvement from baseline.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 5, 2018)

• Proportion of participants who achieve EASI75 [ Time Frame: Up to 8 weeks ]
  Defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI) score.
• Proportion of participants with a ≥ 4-point improvement in Itch Numerical Rating Scale (NRS) score [ Time Frame: Up to 8 weeks ]
• Proportion of participants with a clinically meaningful improvement in the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form - Sleep Disturbance (8b) 24-hour recall score [ Time Frame: Up to 8 weeks ]
• Participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 52 weeks ]
  TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
• Proportion of participants achieving an IGA-TS [ Time Frame: From baseline up to 4 weeks ]
  Defined as IGA score of 0 or 1 with ≥ 2 grade improvement from baseline.
• Proportion of participants achieving an IGA of 0 or 1 at each visit [ Time Frame: Up to 8 weeks ]
• Proportion of participants with a ≥ 4-point improvement in Itch NRS score [ Time Frame: Up to 4 weeks ]
• Proportion of participants who achieve EASI50 at each visit during the VC period. [ Time Frame: Up to 8 weeks ]
  Defined as ≥ 50% improvement in EASI score.
• Proportion of participants who achieve EASI75 [ Time Frame: Up to 4 weeks ]
  Defined as ≥ 75% improvement in EASI score.
• Proportion of participants who achieve EASI90 at each visit during the VC period [ Time Frame: Up to 8 weeks ]
  ≥ 90% improvement in EASI score.
• Mean percentage change from baseline in EASI score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
• Mean percentage change from baseline in SCORAD score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
  SCORing Atopic Dermatitis - tool used to assess extent and severity (intensity) of eczema.
• Change from baseline in Itch NRS score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
  The Itch NRS is a daily patient-reported measure of the worst level of itch intensity. Participants will be asked to rate the itching severity by selecting a number from 0 (no itch) to 10 (worst imaginable itch).
• Time to achieve Itch NRS score improvement of at least 2, 3, or 4 points [ Time Frame: Up to 8 weeks ]
• Change from baseline in Skin Pain NRS score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
  The Skin Pain NRS is a daily patient-reported measure of the worst level of pain intensity from 0 (no pain) to 10 (worst imaginable pain).
• Proportion of participants with a clinically meaningful improvement in the PROMIS Short Form - Sleep-Related Impairment (8a) 24-hour recall score [ Time Frame: Up to 8 weeks ]
• Change from baseline in PROMIS Short Form - Sleep Related Impairment (8a) 24-hour recall and Short Form - Sleep Disturbance (8b) 24-hour recall score [ Time Frame: From baseline up to 8 weeks ]
• PROMIS Short Form - Sleep-Related Impairment (8a) 7-day recall and Short Form - Sleep Disturbance (8b) 7-day recall score [ Time Frame: Up to 52 weeks ]
• Change from baseline in AD afflicted percentage of body surface area (%BSA) at every visit [ Time Frame: From baseline up to 52 weeks ]
• Change from baseline in Patient-Oriented Eczema Measure (POEM) score at each visit [ Time Frame: From baseline up to 52 weeks ]
  The POEM is a 7-question quality-of-life assessment that asks how many days the participant has been bothered by various aspects of their skin condition during the past 7 days.
• Change from baseline in Dermatology Life Quality Index (DLQI) score [ Time Frame: From baseline up to 52 weeks ]
  The DLQI is a 10-question validated questionnaire to measure how much the skin problem has affected the participant over the previous 7 days. The participant will answer the questionnaire with either (1) very much, (2) a lot, (3) a little, or (4) not at all.
• Mean Patient Global Impression of Change (PGIC) score [ Time Frame: Up to 8 weeks ]
  The PGIC is based on a 7-point scale and the participant will rate each question from the start of treatment as 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5-minimally worse, 6-much worse, and 7-very much worse.
• Proportion of participants with each score on the PGIC [ Time Frame: Up to 8 weeks ]
  The PGIC is based on a 7-point scale and the participant will rate each question from the start of treatment as 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5-minimally worse, 6-much worse, and 7-very much worse.
• Proportion of participants with a score of either 1 or 2 on the PGIC [ Time Frame: Up to 8 weeks ]
  The PGIC is based on a 7-point scale and the participant will rate each question from the start of treatment as 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5-minimally worse, 6-much worse, and 7-very much worse.
• Change from baseline in EQ-5D-5L score during the VC period [ Time Frame: From baseline up to 8 weeks ]
  EQ-5D is a validated, self-administered, generic, utility questionnaire wherein participants will rate their current health state based on the following criteria: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The 5L indicates that for each dimension, there are 5 levels, which are as follows: no problems, slight problems, moderate problems, severe problems, and extreme problems. The digits for the 5 dimensions can be combined into a 5-digit number that describes the participant's health state.
• Change from baseline in WPAI-SHP v2.0 [ Time Frame: From baseline up to 52 weeks ]
  Work Productivity and Activity Impairment Questionnaire: Specific Health Problem Version 2.0. The WPAI:SHP v2.0 questionnaire is a validated 6-item instrument, completed that measures the effect of overall health and specific symptoms on productivity at work and regular activities outside of work.
• Trough plasma concentrations of ruxolitinib at all study visits [ Time Frame: Up to 52 weeks ]

Original Secondary Outcome Measures (submitted: November 15, 2018)

• Proportion of participants who achieve EASI75 [ Time Frame: Up to 8 weeks ]
  Defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI) score.
• Proportion of participants with a ≥ 4-point improvement in Itch Numerical Rating Scale (NRS) score [ Time Frame: Up to 8 weeks ]
• Proportion of participants with a clinically meaningful improvement in the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form - Sleep Disturbance (8b - 24-hour recall) score [ Time Frame: Up to 8 weeks ]
• Participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 52 weeks ]
  TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
• Proportion of participants achieving an IGA-TS [ Time Frame: From baseline up to 4 weeks ]
  Defined as IGA score of 0 or 1 with ≥ 2 grade improvement from baseline.
• Proportion of participants achieving an IGA of 0 or 1 at each visit [ Time Frame: Up to 8 weeks ]
• Proportion of participants with a ≥ 4-point improvement in Itch NRS score [ Time Frame: Up to 4 weeks ]
• Proportion of participants who achieve EASI50 at each visit during the vehicle-controlled (VC) period. [ Time Frame: Up to 8 weeks ]
  Defined as ≥ 50% improvement in EASI score.
• Proportion of participants who achieve EASI75 [ Time Frame: Up to 4 weeks ]
  Defined as ≥ 75% improvement in EASI score.
• Proportion of participants who achieve EASI90 at each visit during the VC period [ Time Frame: Up to 8 weeks ]
  ≥ 90% improvement in EASI score.
• Mean percentage change from baseline in EASI score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
• Mean percentage change from baseline in SCORAD score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
  SCORing Atopic Dermatitis - tool used to assess extent and severity (intensity) of eczema.
• Change from baseline in Itch NRS score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
• Time to achieve Itch NRS score improvement of at least 2, 3, or 4 points [ Time Frame: Up to 8 weeks ]
• Change from baseline in Skin Pain NRS score at each visit during the VC period [ Time Frame: From baseline up to 8 weeks ]
• Proportion of participants with a clinically meaningful improvement in the PROMIS Short Form - Sleep-Related Impairment (8a) 24-hour recall score [ Time Frame: Up to 8 weeks ]
• Change from baseline in PROMIS Short Form - Sleep Related Impairment (8a) 24-hour recall and Short Form - Sleep Disturbance (8b) 24-hour recall score [ Time Frame: From baseline up to 8 weeks ]
• PROMIS Short Form - Sleep-Related Impairment (8a) 7-day recall and Short Form - Sleep Disturbance (8b) 7-day recall score [ Time Frame: Up to 52 weeks ]
• Change from baseline in AD afflicted percentage of body surface area (%BSA) at every visit [ Time Frame: From baseline up to 52 weeks ]
• Change from baseline in Patient-Oriented Eczema Measure (POEM) score at each visit [ Time Frame: From baseline up to 52 weeks ]
• Change from baseline in Dermatology Life Quality Index (DLQI) score [ Time Frame: From baseline up to 52 weeks ]
• Mean Patient Global Impression of Change (PGIC) score [ Time Frame: Up to 8 weeks ]
• Proportion of participants with each score on the PGIC [ Time Frame: Up to 8 weeks ]
• Proportion of participants with a score of either 1 or 2 on the PGIC [ Time Frame: Up to 8 weeks ]
• Change from baseline in EQ-5D-5L score during the VC period [ Time Frame: From baseline up to 8 weeks ]
  EQ-5D is a validated, self-administered, generic, utility questionnaire wherein participants will rate their current health state based on the following criteria: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
• Change from baseline in WPAI-SHP v2.0 [ Time Frame: From baseline up to 52 weeks ]
  Work Productivity and Activity Impairment Questionnaire: Specific Health Problem Version 2.0.
• Trough plasma concentrations of ruxolitinib at all study visits [ Time Frame: Up to 52 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Brief Summary: The purpose of this study is to assess the efficacy and safety of ruxolitinib cream in adolescents and adults with atopic dermatitis (AD).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis

Intervention

• Drug: Ruxolitinib cream
  Ruxolitinib cream 1.5% or 0.75% applied as a thin film twice daily (BID) (vehicle-controlled (VC) and long-term safety extension periods).
  Other Name: INCB018424 phosphate cream
• Drug: Vehicle cream
  Matching vehicle cream applied as a thin film BID (VC period only).

Study Arms

• Experimental: Ruxolitinib cream
  Intervention: Drug: Ruxolitinib cream
• Placebo Comparator: Vehicle cream
  Intervention: Drug: Vehicle cream

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 1, 2019): 618
• Original Estimated Enrollment (submitted: November 15, 2018): 600
• Actual Study Completion Date: November 9, 2020
• Actual Primary Completion Date: November 18, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adolescents aged ≥ 12 to 17 years, inclusive, and men and women aged ≥ 18 years.
• Participants diagnosed with AD as defined by the Hanifin and Rajka criteria.
• AD duration of at least 2 years.
• Participants with an IGA score of 2 to 3 at screening and baseline (VC period) and 0 to 4 at Week 8 (long-term safety period).
• Participants with %BSA (excluding scalp) of AD involvement of 3% to 20% at screening and baseline (VC period) and 0% to 20% at Week 8 (long-term safety 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 JAK inhibitors, systemic or topical.
• Ultraviolet 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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Canada, Czechia, Germany, Poland, Spain, United States

Administrative Information

• NCT Number: NCT03745651
• Other Study ID Numbers: INCB 18424-304
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Incyte Corporation
• Study Sponsor: Incyte Corporation
• Collaborators: Not Provided

Investigators

• Study Director: Michael E. Kuligowski, MD, PhD, MBA; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: November 2020