Efficacy of Baricitinib in Treating New-Onset Juvenile Dermatomyositis: A Phase II Clinical Trial

The primary objective of this study is to evaluate the **efficacy** of baricitinib in patients with new-onset **Juvenile Dermatomyositis (JDM)** at week 24, as measured by the PRINTO 20 level of improvement. This is clinically relevant as it aims to determine the potential of baricitinib to improve disease outcomes in JDM, a rare and debilitating inflammatory condition affecting children.

Secondary objectives include:

• Assessing the efficacy of baricitinib at weeks 4, 8, 12, 16, and 24 according to PRINTO 50, 70, and 90 levels of improvement.
• Determining the response rate to baricitinib using the Total Improvement Score (TIS) based on the 2016 American College of Rheumatology/European League myositis response criteria.
• Evaluating the efficacy of baricitinib according to the PRINTO criteria of clinically inactive disease.
• Assessing the efficacy of baricitinib on JDM-related skin disease using the cutaneous DM disease area and severity index (CDASI).
• Evaluating the efficacy of baricitinib on global disease activity of various extramuscular organ systems using the Myositis Disease Activity Assessment VAS (MYOACT).
• Assessing the efficacy of baricitinib on interstitial lung disease.
• Evaluating the safety of baricitinib.
• Assessing the reduction in oral corticosteroids at week 24.
• Characterizing the pharmacokinetics of baricitinib in children with JDM.
• Assessing a correlation between pharmacokinetics and response to baricitinib at week 24.
• Identifying biomarkers of JDM activity and predictive biomarkers of response to baricitinib, including cytokine levels and gene expression related to immunity.
• Assessing a correlation between the muscle biopsy score and the response to baricitinib.

The clinical trial involves participants diagnosed with **Juvenile Dermatomyositis**, a condition characterized by muscle weakness and skin rash. The study population includes both male and female subjects aged between 3 to 18 years, with a focus on those experiencing new-onset symptoms. Participants were selected based on specific criteria, including muscle weakness as measured by MMT and/or CMAS, and seropositivity or vaccination for chickenpox. The trial includes a vulnerable population, as it involves children and adolescents. The sponsor has not provided information regarding the total number of participants. Participants are required to be affiliated with a social security regime and, for those of childbearing age, to use effective contraception methods. The trial aims to assess the efficacy of baricitinib over a 24-week period.

The clinical trial is designed to evaluate the efficacy of **baricitinib** in patients with new-onset **juvenile dermatomyositis**. This is a phase II, open-label, multicentric study. The trial will involve a randomized, controlled design to ensure the reliability of the results. The estimated duration of the trial is from November 2022 to June 2026, with a maximum treatment period of 24 weeks for each participant. Participants will be children aged 3-18 years who meet the ENMC 2018 dermatomyositis classification criteria and exhibit muscle weakness. The primary endpoint is the achievement of the PRINTO 20 level of improvement at week 24, defined as a 20% or greater improvement in three or more of the six variables of the juvenile dermatomyositis core set, with one or no variable worsening by more than 30%.

The study will include several visits to monitor the participants' progress and ensure their safety. The initial visit will be a screening visit to confirm eligibility based on the inclusion criteria, such as muscle weakness and seropositivity or vaccination for chickenpox. Follow-up visits will occur at weeks 4, 8, 12, 16, and 24 to assess the primary and secondary endpoints, including the PRINTO 50, 70, and 90 levels of improvement, variations in disease activity scores, and adverse events. The end-of-study visit will occur at week 24, marking the conclusion of the participant's involvement in the trial. Participants are expected to adhere to the study protocol, and any deviation or adverse event may lead to early termination from the study. The trial will also involve the measurement of various biomarkers and the assessment of muscle biopsies to provide comprehensive data on the treatment's efficacy and safety.

The clinical trial involves the use of **baricitinib**, an experimental medication, in the treatment of new-onset juvenile dermatomyositis. **Baricitinib** is a chemical substance with the active substance name **baricitinib** and is also known by the synonyms LY-3009104 and INCB-028050. It is classified under the ATC code L04AA37. The pharmaceutical form of **baricitinib** is identified as PHF00082MIG, and it is administered orally. The maximum daily dose is 4 mg, with a total maximum dose of 672 mg over the treatment period. The maximum treatment period is 24 weeks. The medication is not a pediatric formulation and is not classified as an orphan drug.

In this trial, **baricitinib** is the primary investigational product, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The administration of the drug is monitored to ensure participant compliance with the dosing schedule. The trial aims to assess the efficacy of **baricitinib** in patients with new-onset juvenile dermatomyositis at week 24, according to the PRINTO 20 level of improvement. The study is designed to provide a comprehensive evaluation of the therapeutic potential of **baricitinib** in this patient population.

The efficacy of **baricitinib** in the treatment of new-onset juvenile dermatomyositis will be assessed primarily through the PRINTO 20 level of improvement at week 24. This primary endpoint is defined as a 20% or greater improvement in three or more of the six variables of the juvenile dermatomyositis core set, with one or no variable worsening by more than 30%, ensuring that muscle strength is not the variable worsening. Secondary endpoints include the achievement of PRINTO 20 levels of improvement at weeks 4, 8, 12, and 16, as well as PRINTO 50, 70, and 90 levels of improvement at weeks 4, 8, 12, 16, and 24. Additional secondary endpoints involve the assessment of clinically inactive disease at specified timepoints according to PRINTO criteria, and the relative and absolute variations of TIS, CDSAI, and MYOACT between inclusion and weeks 4, 8, 12, 16, and 24.

Further efficacy assessments will include the improvement of interstitial lung disease, if present at screening, through pulmonary function tests and lung tomodensitometry. The study will also evaluate adverse events, corticosteroid dose at week 24, and conduct a non-compartmental analysis of baricitinib pharmacokinetics (PK). Correlations between baricitinib PK and disease activity scores will be analyzed. Biomarker measurements, including serum levels of IFN-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-22, and TNF-α, will be conducted at inclusion, weeks 4, and 24. Gene expression studies related to immunity will be performed at the same timepoints. Muscle biopsies will be assessed using an internationally validated score system. These comprehensive assessments will provide a detailed evaluation of the efficacy of baricitinib in this patient population.