Evaluation of Baricitinib Pharmacokinetics, Efficacy, and Safety in Pediatric Patients with Moderate-to-Severe Atopic Dermatitis: A Phase 3 Randomized Controlled Trial

The primary objective of this Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study is to evaluate the **efficacy** and **safety** of **Baricitinib** in pediatric patients with moderate-to-severe **Atopic Dermatitis**. This objective is clinically relevant as it aims to determine the therapeutic potential and safety profile of Baricitinib, which could provide a new treatment option for this patient population, addressing an unmet medical need in managing this chronic inflammatory skin condition.

The clinical trial involves a total of **362 participants** diagnosed with **atopic dermatitis**. The study population includes both male and female subjects, ranging in age from 2 years old and above. Participants are required to be at or above the 5th percentile of weight for their age. The trial specifically targets children and teenagers who have been diagnosed with moderate to severe atopic dermatitis for a minimum of 12 months if they are 6 years old or older, or at least 6 months if they are between 2 to 6 years old. Participants must have shown an inadequate response or intolerance to existing topical medications within the 6 months preceding screening. Additionally, they must be willing to discontinue certain treatments for eczema during a washout period and agree to use emollients daily. The trial population was selected based on these criteria to ensure the safety and efficacy of the study drug, Baricitinib, in this vulnerable population. Lifestyle considerations such as the use of emollients are integral to the study, although specific details on diet or physical activity are not provided.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the pharmacokinetics, efficacy, and safety of **Baricitinib** in pediatric patients with moderate-to-severe **atopic dermatitis**. The trial is structured to include multiple phases, beginning with a screening visit to assess eligibility based on specific inclusion criteria, such as a diagnosis of moderate to severe atopic dermatitis for a specified duration and an inadequate response to existing topical treatments. Participants must also agree to discontinue certain eczema treatments during a washout period and use emollients daily. The trial is expected to span from May 24, 2019, to May 22, 2026, with participant involvement lasting up to 268 days, depending on individual response and adherence to the protocol.

Study visits are sequenced to include an initial screening visit, followed by regular follow-up visits to monitor the participants' response to the treatment and any adverse effects. The primary endpoints include the percentage of participants achieving an Investigator's Global Assessment of 0 or 1 with a ≥2 point improvement, and pharmacokinetic measures such as maximum observed drug concentration at steady state. The end-of-study visit will conclude the trial for each participant, assessing the overall safety and efficacy of the treatment. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or the occurrence of significant adverse events. The trial is categorized as a low-intervention study, as the investigational medicinal products are authorized in the EU and used in accordance with their marketing authorization, posing minimal additional risk to participants.

The clinical trial involves the use of several treatments, including **Baricitinib**, **Hydrocortisone**, and **Triamcinolone Acetonide**, as well as placebo controls. **Baricitinib** is administered in two forms: a film-coated tablet and an oral suspension. The film-coated tablet is designed for oral use, with a maximum daily dose of 4 mg and a total maximum dose of 7504 mg over a treatment period of up to 268 days. The oral suspension is also administered orally, with the same dosing parameters. The investigational medicinal product (IMP) is packaged specifically for clinical trial use, with no commercial debossing on the tablets, and is manufactured using the commercial drug substance with the same unit formula as Olumiant. The drug product and excipients may differ in facilities, specifications, methods, shelf-life, and packaging, all of which are appropriate for clinical trial use.

**Hydrocortisone** is utilized in the form of a cream for cutaneous use. It is part of the background therapy and does not have a specified maximum daily or total dose. The treatment period for **Hydrocortisone** is limited to 1 day. The cream is applied topically as needed, and participant compliance is monitored through regular assessments.

**Triamcinolone Acetonide** is also administered as a cream for cutaneous use, serving as part of the background therapy. Similar to **Hydrocortisone**, it does not have a specified maximum daily or total dose and is used for a treatment period of 1 day. The application is topical, and compliance is monitored through participant self-reporting and clinical evaluations.

Placebo treatments are included to match the active treatments, ensuring blinding in the study. These include placebos to match 1 mg, 2 mg, and 4 mg tablets, as well as a placebo to match the 2 mg/ml oral suspension. The placebos are administered in the same manner as their corresponding active treatments, with dosing schedules and compliance monitoring aligned to maintain the integrity of the study's blinding process.

The efficacy of the clinical trial will be assessed using several primary endpoints. These include the percentage of participants achieving an Investigator's Global Assessment (IGA) score of 0 or 1 with a ≥2 point improvement. Additionally, pharmacokinetic parameters will be evaluated, specifically the maximum observed drug concentration at steady state (Cmax,ss) and the area under the concentration-time curve for the dosing interval at steady state (AUCtau,ss) of **Baricitinib** (LY3009104). These endpoints will be measured to determine the effectiveness of the investigational medicinal product in pediatric patients with moderate-to-severe atopic dermatitis.