Efficacy and Safety Evaluation of Apremilast in Pediatric Patients Aged ≥6 Years with Generalized Epidermolysis Bullosa Simplex: A 20-Week Multicenter Study

The primary objective of this study is to evaluate the **efficacy** of apremilast in patients aged 6 years and older with **epidermolysis bullosa simplex** (EBS-sev) over three periods of a challenge-dechallenge-rechallenge design. This is clinically relevant as it aims to determine the therapeutic potential of apremilast in managing EBS-sev, a condition characterized by skin fragility and blistering, which significantly impacts patient quality of life.

Secondary objectives include: - Describing the safety profile of apremilast treatment throughout the study period. - Assessing the evolution of efficacy and health outcomes measures, including severity (patient and clinician global assessment), itch and pain (visual analog scales), duration of dressing, quality of life (QoL) using dermatological scales for both adults and children, and EB severity scores. - Evaluating patient compliance during treatment periods. - Validating a new score developed to assess EBS-sev severity. These objectives are crucial for understanding the broader impact of apremilast on patient health and treatment adherence, as well as for refining assessment tools for EBS-sev severity.

The clinical trial focuses on patients diagnosed with **epidermolysis bullosa simplex** (EBS-sev) due to KRT5 or 14 mutation. The study population includes both male and female participants aged 6 years and older. The sponsor has not provided the total number of participants. Participants are required to have a laboratory-confirmed diagnosis and a mean daily number of new blisters greater than four. The trial does not involve a vulnerable population. Participants are expected to refrain from using any topical therapies not approved by the investigator. The selection criteria ensure that the study population is representative of individuals with EBS-sev, allowing for a comprehensive evaluation of the efficacy of apremilast in this demographic.

The clinical trial is designed to evaluate the **efficacy** and safety of **apremilast** in patients aged 6 years and older with **epidermolysis bullosa simplex** (EBS). This study follows a challenge-dechallenge-rechallenge design over a period of 20 weeks. The trial is categorized as a Phase 4 study, focusing on an authorized drug not used in the specified indication. The trial is open-label and multicenter, with the primary objective being the assessment of apremilast's efficacy in treating EBS. Secondary objectives include evaluating safety, tolerability, and various health outcomes such as severity, itch, pain, duration of dressing, and quality of life. The study also aims to validate a new severity scale for EBS patients.

Participants will be involved in the study for a maximum of 16 weeks, with the treatment administered orally in the form of film-coated tablets. The maximum daily dose is 60 mg. The trial will commence with a screening visit to confirm eligibility, which includes criteria such as a laboratory-confirmed diagnosis of EBS due to KRT5 or 14 mutation and a mean daily number of new blisters greater than four. Participants must agree not to use any topical therapies other than those approved by the investigator. Follow-up visits will be scheduled throughout the study to monitor the participants' response to the treatment and any adverse events. The end-of-study visit will conclude the trial, assessing the overall outcomes and any long-term effects of the treatment.

Participant involvement is expected to last up to 16 weeks, with conditions for early termination including non-compliance with the study protocol, withdrawal of consent, or any adverse events that may compromise the safety of the participant. The trial is set to begin recruitment on June 1, 2024, with an estimated end date of December 31, 2026. The study is authorized in France, and the trial status is currently authorized, with recruitment yet to commence.

The clinical trial involves the administration of **Otezla** (apremilast) in the form of film-coated tablets. The primary experimental medication is Otezla 30 mg film-coated tablets, which contain the active substance **apremilast**, a chemical compound. The pharmaceutical form is a film-coated tablet, and the route of administration is oral. The dosage regimen for this trial involves a maximum daily dose of 60 mg, with a total maximum dose of 60 mg per day. The treatment period is set for a maximum of 16 weeks. The medication is manufactured by Amgen Europe B.V. and is not a paediatric formulation.

In addition to the 30 mg tablets, the trial also includes Otezla film-coated tablets available in 10 mg, 20 mg, and 30 mg dosages. These tablets also contain **apremilast** as the active ingredient, with the same chemical origin. The administration route remains oral, and the maximum daily dose is consistent at 60 mg, with a total maximum dose of 60 mg per day. The treatment duration is similarly capped at 16 weeks. These tablets are also produced by Amgen Europe B.V. and are not formulated for paediatric use.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. Compliance with the dosing schedule is critical, and participant adherence will be monitored throughout the study to ensure the integrity of the trial results. The trial aims to assess the efficacy and safety of apremilast in patients aged 6 years and older with **epidermolysis bullosa simplex generalized**. The study design includes a challenge-dechallenge-rechallenge approach to evaluate the therapeutic effects of the medication.

The efficacy of **apremilast** in the treatment of patients with Epidermolysis Bullosa Simplex generalized (EBS-sev) will be assessed in a 20-week multicenter, open-label study. The primary endpoint is to evaluate the efficacy of apremilast in reducing the severity of EBS-sev. Secondary endpoints include the assessment of safety and tolerability, as well as secondary efficacy and health outcomes measures such as severity, itch, pain, duration of dressing, quality of life, and compliance. Additionally, the study aims to validate a new severity scale for EBS-sev patients.

The study will employ a challenge-dechallenge-rechallenge design to observe the effects of apremilast over three distinct periods. Efficacy parameters will be collected and analyzed throughout the treatment periods, with specific events monitored to assess safety and tolerability. The study will also include a one-week follow-up period to ensure comprehensive data collection. The trial is set to begin recruitment on June 1, 2024, and is estimated to conclude by December 31, 2026.