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

Incyte

Status and phase: Completed; Phase 3

Conditions: Atopic Dermatitis

Treatments: Drug: Vehicle Cream; Drug: Ruxolitinib Cream

Study type: Interventional

Funder types: Industry

Identifiers

NCT03745638

2018-003712-45 (EudraCT Number)

INCB 18424-303

Details and patient eligibility

About

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).

Enrollment: 631 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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631 participants in 7 patient groups, including a placebo group

VC Period: Vehicle Cream BID

Placebo Comparator group

Description:

Participants received vehicle cream, applied topically to the affected areas as a thin film twice daily (BID) from Day 1 to Week 8 during the Vehicle Control (VC) Period. Participants applied cream BID to areas identified at Baseline even if the areas improved.

Treatment:

Drug: Vehicle Cream

VC Period: Ruxolitinib 0.75% Cream BID

Experimental group

Description:

Participants received ruxolitinib 0.75% cream, applied topically to the affected areas as a thin film BID from Day 1 to Week 8 during the VC Period. Participants applied cream BID to areas identified at Baseline even if the areas improved.

Treatment:

Drug: Ruxolitinib Cream

VC Period: Ruxolitinib 1.5% Cream BID

Experimental group

Description:

Participants received ruxolitinib 1.5% cream, applied topically to the affected areas as a thin film BID from Day 1 to Week 8 during the VC Period. Participants applied cream BID to areas identified at Baseline even if the areas improved.

Treatment:

Drug: Ruxolitinib Cream

LTS Period: Vehicle Cream to Ruxolitinib 0.75% Cream BID

Experimental group

Description:

Participants who applied vehicle cream BID during the VC Period, were randomized to apply ruxolitinib 0.75% cream, topically to the affected areas as a thin film BID from Week 8 to 52 during the Long-term Safety (LTS) Period. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence.

Treatment:

Drug: Ruxolitinib Cream

LTS Period: Vehicle Cream to Ruxolitinib 1.5% Cream BID

Experimental group

Description:

Participants who applied vehicle cream BID during the VC Period, were randomized to apply ruxolitinib 1.5% cream, topically to the affected areas as a thin film BID from Week 8 to 52 during the LTS Period. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence.

Treatment:

Drug: Ruxolitinib Cream

LTS Period: Ruxolitinib 0.75% Cream

Experimental group

Description:

Arm description: Participants who applied ruxolitinib 0.75% cream during VC Period, continued applying ruxolitinib 0.75% cream topically to the affected areas as a thin film BID from Week 8 to 52 during the LTS Period. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence.

Treatment:

Drug: Ruxolitinib Cream

LTS Period: Ruxolitinib 1.5% Cream

Experimental group

Description:

Arm description: Participants who applied ruxolitinib 1.5% cream during VC Period, continued applying ruxolitinib 1.5% cream topically to the affected areas as a thin film BID from Week 8 to 52 during the LTS Period. Participants stopped treatment 3 days after lesions disappeared and restarted at the first sign of recurrence.

Treatment:

Drug: Ruxolitinib Cream