Clinical trial NCT05034822: Study of Ruxolitinib Cream in Children With Atopic Dermatitis
Official title: A Maximum Use (MUsT) Pediatric Study of 1.5% Ruxolitinib Cream in Children (Ages ≥ 2 Years to < 12 Years) With Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atopic Dermatitis
Keywords: pediatric
Atopic dermatitis
ruxolitinib cream
maximum use
open label
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: Innovaderm Research
First posted: 2021-09-05
Enrollment: 29
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label maximum use trial to evaluate ruxolitinib safety, tolerability and blood levels after its topical application twice daily to affected areas (≥ 35% BSA) in pediatric participants with atopic dermatitis (AD) and to determine if its systemic bioavailability results in any adverse events.

Detailed description: Open-label, BID application to all affected areas identified at BSLN for 4 weeks (maximum use trial (MUsT) period). The next 4 weeks (treatment extension period) will be applied BID to active lesions only for the next 4 weeks for a total treatment period of 8 weeks. Eligible participants will be offered option to continue into 44-wk LTS period of BID to treat as-needed to active lesions. All participants will have 30 day safety follow-up visit.

Eligibility criteria: Inclusion Criteria:

* Male and female children aged ≥ 2 years to \< 12 years (age at the screening visit).
* Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria.
* AD duration of at least 3 months (participant/parent/guardian may verbally report signs and symptoms of AD with onset at least 3 months prior to screening).
* An IGA score as follows:

  * Treatment period: ≥ 2 at the screening and baseline visits.
  * LTS period: 0 to 4 at Week 8
* %BSA (excluding the scalp) with AD involvement as follows:

  * Treatment period: ≥ 35% at screening and baseline
  * LTS period: 0% to 20% at Week 8
* For children aged 6 years to \< 12 years, mean Itch NRS score ≥ 4 during the screening period.
* Participants/guardians who agree to discontinue all agents used by the participant to treat AD from the screening visit through the final safety follow-up visit.
* At least 1 target lesion that measures approximately 5 cm2 or more at the screening and baseline visits. The target lesion must be representative of the participant's disease state but not located on the face, hands, feet, or genitalia.
* 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 male and female participants who are prepubescent.
* 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.

Exclusion Criteria:

* An unstable course of AD (spontaneously improving or rapidly deteriorating) as determined by the investigator over the previous 4 weeks prior to the baseline visit.
* Concurrent conditions and history of other diseases as follows:

  * Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome,
  * Wiskott-Aldrich syndrome) or a history of malignant disease within 5 years before the baseline visit.
  * Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit.
  * Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chickenpox, clinically infected AD, impetigo) within 1 week before the baseline 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.
  * Other types of eczema.
  * Chronic asthma requiring more than 800 μg/day of inhaled budesonide or equivalent high dose of other inhaled corticosteroids.
  * A medical history of hepatitis B virus or hepatitis C virus infection.
  * Any participant on maintenance dialysis.
* Any of the following clinical laboratory test results at screening:

  * Cytopenias at screening, defined as follows:
  * Hemoglobin \< 10 g/dL
  * ANC \< 1000/µL
  * Platelet count \< 100,000/µL
  * Liver function tests:
  * AST or ALT ≥ 2.5 × ULN
  * Total bilirubin \> 1.5 × ULN (isolated bilirubin \> 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is \< 35%).
  * Estimated GFR \< 30 mL/min/1.73 m2 (using the Modification of Diet in Renal Disease equation)
  * Positive serology test results at screening for HIV antibody.
  * Any other clinically significant laboratory result that, in the opinion of the investigator, pose a significant risk to the participant
* 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 the baseline visit:

  * 5 half-lives or 12 weeks, whichever is longer - biologic agents (eg, dupilumab).
  * 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogues, cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate, choroquine or tacrolimus).
  * 2 weeks - immunizations with live-attenuated vaccines; sedating antihistamines unless on a long-term stable regimen (nonsedating antihistamines are permitted). Note: Live-attenuated vaccines are not recommended during the treatment period of the study. COVID-19 vaccines are allowed during the study.
  * 1 week - use of topical treatments for AD (other than bland emollients, creams, ointments, sprays, soap substitutes), topical antipruritics (eg, doxepin cream), corticosteroids, calcineurin inhibitors, PDE4 inhibitors, coal tar (shampoo), topical 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.
* Previous treatment with systemic or topical JAK inhibitors (eg, ruxolitinib, tofacitinib, baricitinib, filgotinib, lestaurtinib, pacritinib).
* 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, which is thought by the investigator to potentially impact the participant's AD.
* Known or suspected hypersensitivity to either ruxolitinib or any component of its cream vehicle.
* Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before the baseline visit with another investigational medication or current enrollment in another investigational drug protocol.
* Inadequate venous access in nonlesional areas for laboratory blood draws.
* In the opinion of the investigator, unable or unlikely to comply with the administration schedule and study evaluations.

Primary outcomes:
measure: Number of treatment-emergent adverse events
timeFrame: Up to approximately 61 weeks
Secondary outcomes:
measure: Concentration of Ruxolitinib in plasma
timeFrame: Day 1, Weeks 2, 4 and 8
measure: Plasma Css of Ruxolitinib
timeFrame: Weeks 2 and 4
measure: Accumulation ratio of Ruxilitinib
timeFrame: Day 1, Weeks 2, 4 and 8
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Desert Sky Dermatology
state: Arizona
city: Hot Springs National Park
country: United States
facility: Burke Pharmaceutical Research
state: Arkansas
city: Anaheim
country: United States
facility: Orange County Research Center
state: California
city: Hollywood
country: United States
facility: Skin Care Research, Llc Scr Hollywood
state: Florida
city: Lake Mary
country: United States
facility: Accel Clinical Research
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic Inc.
state: Florida
city: Tampa
country: United States
facility: Forward Clinical Trials
state: Florida
city: Sandy Springs
country: United States
facility: Advanced Medical Research Pc
state: Georgia
city: Savannah
country: United States
facility: Aeroallergy Research Lab of Savannah
state: Georgia
city: Auburn Hills
country: United States
facility: Oakland Hills Dermatology Pc
state: Michigan
city: Reno
country: United States
facility: Skin Cancer and Dermatology Institute
state: Nevada
city: Forest Hills
country: United States
facility: Forest Hills Dermatology Group
state: New York
city: Dayton
country: United States
facility: Ohio Pediatric Research Association
state: Ohio
city: Gresham
country: United States
facility: Cyn3Rgy Research - Clinedge - Ppds
state: Oregon
city: San Antonio
country: United States
facility: Progressive Clinical Research
state: Texas
Study officials:
affiliation: Incyte Corporation
name: Haq Nawaz, MD, MPH, MBA, MS
role: STUDY_DIRECTOR
References: