Efficacy and Safety of Ruxolitinib Cream in Pediatric Patients with Moderate Atopic Dermatitis: A Phase 3b Randomized, Double-Blind, Vehicle-Controlled Study

The primary objective is to evaluate the efficacy of ruxolitinib cream in children and adolescents aged 6 to < 18 years with moderate Atopic Dermatitis who have an inadequate response to, are intolerant of, or have contraindications for topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI), thereby addressing an unmet therapeutic need in this population. Secondary objectives are to:

• Further assess the efficacy of ruxolitinib cream in the same patient cohort, including during the disease‑control period;
• Evaluate the safety and tolerability of the study medication;
• Characterize the pharmacokinetic profile of ruxolitinib in plasma;
• Assess health‑related quality of life and other patient‑reported outcomes.

The trial enrolled 68 participants diagnosed with Atopic Dermatitis who were children and adolescents aged 6 to < 18 years, inclusive of both female and male subjects. Eligibility required a documented disease duration of at least 3 months for ages 6–11 years or 2 years for ages 12–< 18 years, an EASI score greater than 7, an IGA score of 3, and involvement of 3‑20 % of body surface area (excluding scalp) at screening. Participants also needed an itch or worst‑itch numeric rating scale score of ≥ 4, and a recent history of inadequate response, intolerance, or contraindication to topical corticosteroids or calcineurin inhibitors. Additional criteria included compliance with contraceptive requirements for sexually active individuals, the ability to provide informed consent/assent, and agreement to discontinue other AD treatments throughout the study. The population comprised otherwise healthy, vulnerable pediatric patients meeting these specific disease‑severity and treatment‑history thresholds.

The study is a Phase 3b, randomized, double-blind, multicenter, vehicle-controlled trial evaluating the efficacy and safety of ruxolitinib 15 g cream versus vehicle cream in participants aged 6 to < 18 years with moderate Atopic Dermatitis. After an initial screening visit to confirm eligibility (including Hanifin‑Rajka criteria, EASI > 7, IGA = 3, BSA 3‑20 % and itch NRS ≥ 4), participants attend a baseline (VC Day 1) visit where study medication is assigned. The treatment period comprises eight weeks of twice‑daily application with scheduled follow‑up visits on Days 2, 3, 7, and at Weeks 2, 4, and 8 to assess primary and secondary endpoints such as EASI75 response, IGA‑TS, and itch score changes. An end‑of‑study visit concludes the investigational period, followed by a safety follow‑up. Participants are involved for approximately ten weeks total, including screening and final safety assessment. Early termination may occur if a participant experiences a serious adverse event, fails to meet compliance requirements, withdraws consent, or requires prohibited concomitant therapy.

The investigational product is Ruxolitinib (INCB018424) cream, a topical cream formulation containing the active substance ruxolitinib. Each application delivers a dose of 15 g and is intended for cutaneous use; the cream is applied to the affected skin areas according to the dosing schedule defined in the study protocol.

The control treatment is a vehicle cream that matches the test product in appearance and excipient composition but contains no active substance or phosphoric acid. The vehicle is applied to the skin in the same manner and quantity as the active cream, providing a double‑blind comparator.

All administrations are performed by the participant or caregiver under guidance from study staff. Application timing and amount are recorded in study diaries, and compliance is assessed by verification of returned product containers and diary entries in accordance with protocol‑defined monitoring procedures.

Efficacy will be evaluated using several clinical endpoints. The primary endpoint is the binary response status of EASI75 at visit‑completion (VC) Week 8, defined as achieving ≥ 75 % improvement in the Eczema Area and Severity Index (EASI) score from baseline. Secondary endpoints include the binary response status of IGA‑TS at VC Week 8 (IGA score of 0 or 1 with ≥ 2‑grade improvement), the binary response status of ITCH4 at VC Week 8 (≥ 4‑point improvement in Itch NRS for participants aged 12 to < 18 years or WI NRS for participants aged 6 to < 12 years), time to first disease exacerbation (DE) in the double‑blind continuation period, time to achieve ITCH4 during the VC period, binary responses of EASI75 and IGA‑TS at each post‑baseline visit (excluding VC Week 8), DLQI‑4/CDLQI‑4 at VC Weeks 2, 4, 8 (≥ 4‑point improvement), changes from baseline in DLQI/CDLQI and POEM scores, and plasma concentrations of ruxolitinib (Ctrough,ss) at VC Week 2 and Week 8 in a pharmacokinetic subset.

Assessments will be performed with validated instruments: EASI for disease severity, Investigator’s Global Assessment (IGA) for overall disease status, numeric rating scales for itch (Itch NRS or WI NRS), Dermatology Life Quality Index (DLQI) or Children’s DLQI (CDLQI) for quality‑of‑life impact, and the Patient‑Oriented Eczema Measure (POEM) for symptom burden. Measurements will be collected at baseline and at predefined time points including Days 2, 3, 7, VC Weeks 2, 4, 8, and additional post‑baseline visits for binary response evaluations. Plasma samples for pharmacokinetic analysis will be drawn at VC Week 2 and Week 8.

Binary response rates will be compared between the ruxolitinib cream and vehicle groups using appropriate proportion tests. Time‑to‑event endpoints (first DE, time to ITCH4) will be analyzed with survival‑type methods. Changes from baseline in continuous outcomes (DLQI/CDLQI, POEM) will be evaluated using mixed‑model repeated‑measures or analogous statistical approaches, with safety parameters monitored concurrently.