GENEPID: A 44-weeks monocentric open study assessing the efficacy and safety of Deucravacitinib in adults with Inflammatory EPidermal GENodermatoses (epidermolysis bullosa simplex and inflammatory congenital ichthyoses)

The primary objective of this study is to describe the **efficacy** of deucravacitinib over the three periods of a challenge-dechallenge-rechallenge design in adults with inflammatory congenital ichthyosis, erythrodermic congenital ichthyosis, severe keratinopathic ichthyosis, or severe simplex epidermolysis bullosa. This objective is clinically relevant as it aims to evaluate the therapeutic potential of deucravacitinib in managing these complex and severe dermatological conditions, which are characterized by significant morbidity and impact on quality of life.

Secondary objectives include: - Describing the **safety** of deucravacitinib treatment over the study period. - Describing the evolution of efficacy and health outcomes measures, such as severity, itch, pain, and quality of life, within each study period. - Studying patients' compliance during treatment periods. - Describing cytokines evolution over the study follow-up.

The clinical trial involves **adult** participants diagnosed with **inflammatory epidermal genodermatoses**, specifically targeting individuals with inflammatory congenital ichthyosis, erythrodermic congenital ichthyosis, severe keratinopathic ichthyosis, or severe simplex epidermolysis bullosa. The study population includes both male and female subjects over the age of 18, with a confirmed laboratory diagnosis of the specified conditions due to genetic mutations. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. Participants were selected based on their medical condition and genetic confirmation, adhering to the principal inclusion criteria. The trial aims to evaluate the efficacy of deucravacitinib in this specific patient group.

The clinical trial is designed to evaluate the **efficacy** and safety of **deucravacitinib** in adults with **inflammatory epidermal genodermatoses**, specifically targeting conditions such as epidermolysis bullosa simplex and inflammatory congenital ichthyoses. This is a Phase 4, monocentric, open-label study with a challenge-dechallenge-rechallenge design, spanning a total duration of 44 weeks. The trial will involve a series of study visits, beginning with an inclusion visit where participants will be screened based on specific criteria, including being over 18 years of age and having a laboratory-confirmed diagnosis of the relevant conditions due to specific genetic mutations.

Participants will be administered deucravacitinib in the form of a film-coated tablet, with a maximum daily dose of 6 mg, taken orally. The study is structured into three distinct periods, each serving to assess the primary endpoint of efficacy in treating the specified conditions, alongside secondary endpoints such as safety, severity, itch, pain, quality of life, compliance, and cytokine profile. Follow-up visits will be scheduled throughout the trial to monitor these parameters and ensure participant safety.

The expected length of participant involvement is up to 44 weeks, with the possibility of early termination if adverse effects are observed or if the participant withdraws consent. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the overall outcomes of the treatment. The trial is not classified as low intervention, and the treatment is used outside of its authorized marketing application. Participants' involvement is crucial for the comprehensive assessment of deucravacitinib's therapeutic potential in these rare dermatological conditions.

The clinical trial involves the administration of **deucravacitinib**, a chemical compound developed by Bristol-Myers Squibb International Corporation. Deucravacitinib is provided in the form of a **film-coated tablet**. The active substance, deucravacitinib, is chemically synthesized and is also known by its synonyms BMS986165 and 6-((cyclopropylcarbonyl)amino]-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-((2H3)methyl)pyridazine-3-carboxamide. The pharmaceutical form of the medication is a film-coated tablet, designed for **oral use**. The maximum daily dose is 6 mg, with a total maximum dose of 6 mg per day. The treatment period is set for a maximum of 32 weeks. The medication is not formulated for pediatric use and is not classified as an orphan drug.

In this study, deucravacitinib is the primary investigational product, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial is designed to assess the efficacy and safety of deucravacitinib in adults with inflammatory congenital ichthyosis, erythrodermic congenital ichthyosis, severe keratinopathic ichthyosis, or severe simplex epidermolysis bullosa. The study follows a challenge-dechallenge-rechallenge design to evaluate the therapeutic effects of the medication over the specified treatment period. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

The efficacy of **deucravacitinib** in the treatment of adults with inflammatory congenital ichthyosis, erythrodermic congenital ichthyosis, severe keratinopathic ichthyosis, or severe simplex epidermolysis bullosa will be assessed in a clinical trial. The primary endpoint is to evaluate the efficacy of deucravacitinib in these patient populations. Secondary endpoints include safety assessments, as well as measures of severity, itch, pain, quality of life, compliance, and baseline and functional cytokine profiles.

The study employs a challenge-dechallenge-rechallenge design over three periods, with efficacy parameters being collected and analyzed throughout the trial duration. The trial is planned to last for 44 weeks, with the maximum treatment period for deucravacitinib set at 32 weeks. Efficacy assessments will be conducted using validated scales and laboratory tests to ensure accurate and reliable data collection. The trial is categorized as a Phase 4 study, focusing on treatment efficacy and safety in a real-world setting.