I4V-MC-JAIO: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of Baricitinib in Children from 6 Years to less than 18 Years of Age with Alopecia Areata

The primary objective of this Phase 3, double-blind, randomized, placebo-controlled trial is to evaluate the **efficacy** of high-dose and low-dose **baricitinib** compared to placebo in the treatment of pediatric participants with **alopecia areata** (AA). This objective is clinically relevant as it aims to determine the potential of baricitinib as a therapeutic option for children aged 6 to less than 18 years suffering from AA, a condition characterized by hair loss that can significantly impact quality of life and psychological well-being.

The clinical trial involves a total of **351 participants** diagnosed with **alopecia areata (AA)**. The study population includes both male and female subjects, with an age range of 2 to 17 years, indicating a focus on pediatric participants. The trial population was selected based on specific criteria, including having severe AA for at least one year, with a current episode lasting at least six months and involving significant scalp hair loss. Participants with a history of severe AA for eight years or more may be included if there have been episodes of hair regrowth. The trial does not specify particular lifestyle considerations such as diet or physical activity. The study includes a vulnerable population, as it involves pediatric subjects. The selection criteria ensure that participants have a significant and well-documented history of the condition, which is crucial for evaluating the efficacy of the treatment being tested.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy, safety, and pharmacokinetics of **baricitinib** in pediatric participants aged 6 to less than 18 years with **alopecia areata**. The trial aims to test the hypothesis that both high and low doses of baricitinib are superior to placebo in treating this condition. The study is expected to run until October 2029, with recruitment starting in August 2023. Participants will be involved for a maximum treatment period of 136 weeks, with the possibility of early termination if specific conditions arise, such as adverse reactions or non-compliance with the study protocol.

Study visits are structured to ensure comprehensive data collection and participant safety. The inclusion visit, or screening, will assess eligibility based on criteria such as having severe alopecia areata for at least one year and a current episode of hair loss covering 50% or more of the scalp. Following successful screening, participants will be randomized to receive either baricitinib or a matching placebo. Follow-up visits will occur at regular intervals to monitor treatment response and safety, with the primary endpoint being the percentage of participants achieving a Severity of Alopecia Tool (SALT) score of 20 or less. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any ongoing health concerns are addressed.

Throughout the trial, participants will receive the investigational product in the form of tablets or oral suspension, with a maximum daily dose of 4 mg. The study will utilize an oral syringe and bottle adapter for the administration of the oral suspension. The trial's design ensures that all investigational products, including the placebo, are appropriately packaged and manufactured for clinical trial use, maintaining the integrity and reliability of the study outcomes.

The clinical trial involves the administration of **Baricitinib**, a chemical compound, in various pharmaceutical forms. The primary experimental medication is **Baricitinib** in tablet form, with a maximum daily dose of 4 mg and a total maximum dose of 3808 mg over a treatment period of 136 days. The tablets are administered orally. The sponsor product code for this formulation is LY3009104, and it is manufactured by Eli Lilly and Company Limited. The trial also includes a film-coated tablet form of **Baricitinib**, which is similarly administered orally with the same dosing regimen. This formulation is packaged specifically for clinical trial use, with no commercial debossing on the tablets, and is manufactured using the commercial drug substance as Olumiant.

Additionally, the trial includes a pediatric formulation of **Baricitinib** in the form of an oral suspension. This formulation is also administered orally, with the same dosing schedule as the tablet forms. The oral suspension is accompanied by an oral syringe and bottle adapter, which are CE marked and provided by DEKRA Certification GmbH. This pediatric formulation is designed to facilitate administration in children aged 6 to less than 18 years with alopecia areata.

A placebo is used as a comparator in the trial to match the experimental medication LY3009104. The placebo is designed to mimic the appearance and administration route of the active medication but contains no active substance. The use of a placebo allows for a double-blind, randomized, placebo-controlled trial design, which is essential for evaluating the efficacy and safety of **Baricitinib** in the target pediatric population.

The efficacy of **Baricitinib** in the treatment of pediatric participants with **Alopecia Areata** will be assessed in a Phase 3, double-blind, randomized, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the percentage of participants achieving an absolute Severity of Alopecia Tool (SALT) score of ≤ 20. This endpoint will be used to determine the effectiveness of both high and low doses of Baricitinib compared to placebo.

Participants will be evaluated for efficacy based on the improvement in their SALT scores, which is a validated scale used to measure the extent of scalp hair loss. The trial will include children aged 6 to less than 18 years who have severe Alopecia Areata for at least one year, with a current episode lasting at least six months and involving hair loss of 50% or more of the scalp. The trial is designed to confirm the hypothesis that Baricitinib is superior to placebo in this patient population.