A Study to Assess the Efficacy and Safety of Ruxolitinib Cream in Children and Adolescents (6 to <18 Years Old) With Moderate Atopic Dermatitis (TRuE-AD5)

Incyte

Status and phase: Not yet enrolling; Phase 3

Conditions: Atopic Dermatitis

Treatments: Drug: Vehicle Cream; Drug: Ruxolitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06832618

INCB018424-316

Details and patient eligibility

About

The purpose of the study is to assess the efficacy and safety of ruxolitinib cream in children and adolescents (6 to <18 Years Old) with moderate atopic dermatitis.

Enrollment: 240 estimated patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged 6 to < 18 years at the VC Day 1 visit.

• Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria.

• AD duration of at least 3 months for 6 to 11 year olds and at least 2 years for 12 to < 18 year olds (participant/parent/guardian may verbally report signs and symptoms of AD).

• EASI score > 7 at the screening and VC Day 1 visits.

• IGA score of 3 at the screening and VC Day 1 visits.

• Percent BSA (excluding the scalp) with AD involvement of at least 3% and up to 20% at the screening and VC Day 1 visits.

• Itch NRS or WI NRS score ≥ 4 at the screening and VC Day 1 visits, defined as the average of the 7 days directly before the VC/Day 1 visit, with Itch NRS or WI NRS values available for at least 4 of the 7 days.

• Documented recent history (within 12 months before the screening visit) of inadequate response, intolerance, or contraindication to TCSs and TCIs as follows:

  • Inadequate response:

    • For TCSs: Inability of a given TCS to induce and maintain remission or to contain the AD severity at an acceptable level (comparable to an IGA score of 0 [clear] or 1 [almost clear]) despite treatment for 28 days or for the maximum duration recommended by the product prescribing information (eg, 14 days for superpotent TCSs), whichever is shorter and
    • For TCIs: Inability of a given TCI to induce and maintain remission or to contain the AD severity at an acceptable level (comparable to an IGA score of 0 [clear] or 1 [almost clear]) despite treatment according to the product prescribing information.

Note: Documented (within 12 months before the screening visit) systemic treatment for AD (eg, oral corticosteroids, cyclosporine, methotrexate, azathioprine, mycophenolate mofetil) or phototherapy or photo(chemo)therapy can also be considered as a surrogate for inadequate response to TCSs and TCIs.

• Intolerance: Clinically relevant side effects, safety risks, or skin tolerability issues that outweigh the potential treatment benefits and are the reason why a topical treatment could not be restarted or continued.

Note: Documented history (more than 12 months prior to the screening visit) of clinically significant adverse reactions with use of TCSs and/or TCIs that in the opinion of the investigator outweigh the benefits of restarting treatment would also be considered as evidence of intolerance.

• Contraindication: As defined in the product prescribing information.

• Agreement by participants and guardians to discontinue all agents used by the participant to treat AD from the screening visit through the final safety follow-up visit, except as outlined in the protocol.
• For sexually active participants, willingness to take appropriate contraceptive measures to avoid pregnancy or fathering a child for the duration of study participation with the exception of prepubescent participants.

Note: Female participants who have reached menarche must have a negative urine pregnancy test at the screening and baseline visits before the first application of study cream at baseline. They must also take appropriate precautions to avoid pregnancy from the screening visit through the safety follow-up visit.

• Ability to comprehend and willingness to sign an ICF or written informed consent of the parent(s) or legal guardian and a verbal or written assent from the participant when possible.

Note: A signed written ICF must be obtained for inclusion; see protocol.

Exclusion criteria

• Unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator in the 4 weeks prior to the VC Day 1 visit.

• 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 the VC Day 1 visit.
  • Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chickenpox) within 1 week before the VC Day 1 visit.
  • 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:

    • Absolute neutrophil count < 1000/μL.
    • Platelet count < 100,000/μL.
    • AST or ALT ≥ 2 × ULN.
    • Alkaline phosphatase > 1.5 × ULN.
    • Bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin isfractionated and direct bilirubin < 35%) with the exception of Gilbert disease.

  • Estimated glomerular filtration rate < 30 mL/min/1.73 m2 (using the Modification of Diet in Renal Disease 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 the VC Day 1 visit:

  • 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 (eg, mycophenolate or tacrolimus) agents.
  • 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.
• Pregnant or lactating participants or those considering pregnancy during the period of their study participation.
• Living with anyone participating in any current Incyte-sponsored ruxolitinib cream study.
• Known allergy or reaction to any component of the study cream formulation.
• In the opinion of the investigator, unable or unlikely to comply with the administration schedule, study evaluations, and procedures (eg, eDiary compliance).
• Committed to a mental health institution by virtue of an order issued either by the judicial or the administrative authorities.
• Employees of the sponsor, sponsor delegates (eg, contract research organizations), or investigators or are otherwise dependents of them.
• The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection, or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code.
• In the EU, participants considered incapacitated (according to CTR Article 31).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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240 participants in 6 patient groups, including a placebo group

Vehicle-controlled (VC) Period: Ruxolitinib (1.5% Cream)

Experimental group

Description:

Study drug will be administered twice daily.

Treatment:

Drug: Ruxolitinib

VC Period: Vehicle Cream

Placebo Comparator group

Description:

Matching vehicle cream will be administered twice daily.

Treatment:

Drug: Vehicle Cream

Disease Control (DC) Period: Ruxolitinib (1.5% Cream)

Experimental group

Description:

Study drug will be administered twice weekly.

Treatment:

Drug: Ruxolitinib

DC Period: Vehicle Cream

Placebo Comparator group

Description:

Matching vehicle cream will be administered twice weekly.

Treatment:

Drug: Vehicle Cream

DC Period: Open Label - Ruxolitinib (1.5% Cream)

Experimental group

Description:

Study drug will be administered twice daily to treat Disease Exacerbations.

Treatment:

Drug: Ruxolitinib

Open-label Extension (OLE) period: Ruxolitinib (1.5% Cream)

Experimental group

Description:

Study drug will be administered twice daily.

Treatment:

Drug: Ruxolitinib