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

The primary objective of this study is to establish the **efficacy** of ruxolitinib cream in adults with moderate **Atopic Dermatitis** (AD) who have shown an inadequate response to, are intolerant to, or have contraindications to topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). This is clinically relevant as it addresses the need for alternative treatments in patients who do not respond to or cannot tolerate standard therapies, potentially improving disease management and patient outcomes.

Secondary objectives include:

• Further assessing the treatment effects of ruxolitinib cream in the specified patient population.
• Evaluating the safety and tolerability of ruxolitinib cream in these patients.
• Further evaluating the efficacy of ruxolitinib cream in this context.
• Assessing quality of life and other patient-reported outcomes (PROs) in participants with moderate AD who have an inadequate response to, or are intolerant to, or contraindicated to TCSs and TCIs.

The clinical trial involves a total of **93 participants** diagnosed with **Atopic Dermatitis**. The study population includes both male and female adults aged 18 years and older. Participants were selected based on their diagnosis of moderate atopic dermatitis, with a documented history of inadequate response, intolerance, or contraindication to topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). The trial includes individuals with an Investigator's Global Assessment (IGA) score of 3, an Eczema Area and Severity Index (EASI) score greater than 7, and an Itch Numeric Rating Scale (NRS) score of at least 4. Participants also have a Dermatology Life Quality Index (DLQI) score greater than 10 and a body surface area (BSA) involvement of 10% to 20%, excluding the scalp. The study requires participants to discontinue all agents used to treat atopic dermatitis during the trial period, except as specified in the protocol. Additionally, participants must agree to avoid pregnancy, breastfeeding, or fathering children during and after the trial as per the specified guidelines. The trial population includes a vulnerable group, ensuring comprehensive safety and ethical considerations are in place.

The clinical trial is designed as a **randomized**, **double-blind**, vehicle-controlled study to evaluate the efficacy and safety of **ruxolitinib** cream in adults with moderate **atopic dermatitis**. The trial will involve multiple centers and is categorized as a Phase 3b study. Participants will be randomly assigned to receive either the active treatment, ruxolitinib cream, or a vehicle cream that lacks the active substance. The trial aims to establish the efficacy of ruxolitinib cream in participants who have shown an inadequate response to, or are intolerant to, or contraindicated to topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs).

The trial will span approximately 24 weeks, with the estimated recruitment start date set for September 10, 2024, and an estimated end date of December 15, 2025. Participants will be involved in the study for the entire duration unless early termination is warranted due to adverse events, non-compliance, or withdrawal of consent. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, diagnosis, and disease severity; baseline assessments on Day 1; and subsequent follow-up visits to monitor efficacy and safety outcomes. The primary endpoint will be assessed at Week 8, focusing on the proportion of participants achieving a 75% improvement in the Eczema Area and Severity Index (EASI75) and an Investigator's Global Assessment Treatment Success (IGA-TS) score of 0 or 1 with a ≥ 2-grade improvement from baseline.

Secondary endpoints will include the proportion of participants achieving a ≥ 4-point improvement in the Itch Numeric Rating Scale (ITCH4) from baseline to various time points, as well as assessments of adverse events, changes in vital signs, and laboratory data. Participants will also be evaluated for improvements in quality of life measures such as the Dermatology Life Quality Index (DLQI) and other patient-reported outcomes. The study will ensure that participants adhere to specific guidelines, including discontinuation of other atopic dermatitis treatments and adherence to pregnancy prevention measures. The trial will be conducted in accordance with ethical standards, and participants will be required to provide informed consent prior to enrollment.

The clinical trial involves the use of **Ruxolitinib** cream, an experimental medication formulated as a topical cream. The active substance in this formulation is **Ruxolitinib**, a chemical compound known for its therapeutic potential in treating moderate atopic dermatitis. The cream is applied cutaneously, with a maximum daily dose of 15 grams and a total maximum dose of 2520 grams over a treatment period of 24 weeks. The cream is manufactured by Incyte Corporation and is identified by the sponsor product code INCB018424. The administration of the cream is monitored to ensure participant compliance with the dosing schedule.

In addition to the experimental treatment, the study employs a **vehicle cream** as a comparator. This vehicle cream shares the same formulation as the Ruxolitinib cream but lacks the active substance. It serves as a placebo to evaluate the efficacy and safety of the Ruxolitinib cream. The vehicle cream is also applied cutaneously, following the same administration route as the experimental treatment. The use of the vehicle cream allows for a controlled comparison to assess the therapeutic benefits of the active treatment.

The efficacy of **Ruxolitinib** cream in the treatment of moderate atopic dermatitis will be assessed through a series of primary and secondary endpoints. The primary endpoints include the proportion of participants achieving EASI75, defined as a ≥ 75% improvement in the Eczema Area and Severity Index (EASI) score from baseline at Week 8, and the proportion of participants achieving IGA-TS, defined as an Investigator's Global Assessment (IGA) score of 0 or 1 with a ≥ 2-grade improvement from baseline at Week 8.

Secondary endpoints will evaluate additional efficacy parameters, such as the proportion of participants achieving ITCH4, defined as a ≥ 4-point improvement in the Itch Numeric Rating Scale (NRS) score, at various timepoints including Day 2, Day 3, Day 7, and Week 8. Other secondary measures include the type, frequency, and severity of adverse events, changes in vital signs, and laboratory data for hematology and serum chemistry. The study will also assess the proportion of participants achieving EASI75 and IGA-TS at each postbaseline visit, excluding Week 8, and the time to achieve ITCH4 and ITCH2 during the vehicle-controlled period.

Additional assessments will include changes from baseline in Dermatology Life Quality Index (DLQI) scores, Patient-Oriented Eczema Measure (POEM), EQ-5D-5L, Hospital Anxiety and Depression Scale (HADS), and PROMIS Short Form scores related to sleep impairment and disturbance. These efficacy parameters will be measured and collected at specified timepoints throughout the study, ensuring a comprehensive evaluation of the treatment's impact on the participants' condition.