Assessment of Filgrastim Efficacy in Patients with Severe Bullous Drug Eruptions: Lyell Syndrome and Stevens-Johnson Syndrome

The primary objective of this study is to compare the cessation of disease progression after 5 days of treatment in patients with **Stevens-Johnson syndrome (SJS)** and **Lyell syndrome** (Toxic Epidermal Necrolysis, TEN) between two groups: the experimental arm receiving **filgrastim** in addition to the reference symptomatic treatment (FILGRASTIM group) and the control arm receiving only the reference symptomatic treatment combined with placebo (CONTROL group). This objective is clinically relevant as it aims to determine the efficacy of filgrastim in halting the progression of these severe bullous drug eruptions, potentially improving patient outcomes and reducing morbidity.

Secondary objectives include: - Assessment of time to cessation of disease progression since initiation of treatment between FILGRASTIM and CONTROL treatment arms. - Evaluation of time to complete re-epidermalization between the treatment arms. - Evaluation of overall survival at day 30 and up to 365 days between the treatment arms. - Evaluation of the number of days of hospitalization corresponding to the SJS/TEN episode between the treatment arms. - Assessment of the frequency of clinical or biological adverse events leading to premature discontinuation of filgrastim treatment. - Assessment of the total number per patient and the nature of clinical or biological adverse events observed during patient management in each treatment arm. - Assessment of the use of systemic corticosteroid therapy in each treatment arm. - Assessment of the presence of ophthalmological, stomatological/ORL, gastroenterological, gynecological, urological, and psychiatric sequelae. - Assessment of patient quality of life. - Assessment of the risk of developing post-traumatic stress disorder (PTSD).

The clinical trial involves participants diagnosed with **Stevens-Johnson syndrome** (SJS) or Lyell syndrome, also known as toxic epidermal necrolysis (TEN). The study population includes both male and female subjects aged 6 years and older. Participants are required to have SJS or TEN of a proven or strongly suspected drug or infectious origin, with the condition evolving for less than 7 days and showing progression within the last 48 hours. The trial includes a vulnerable population, as it involves minors and individuals in potentially life-threatening situations. Participants must be capable of understanding the trial's objectives and provide written consent, with guardians providing consent for minors. Women of childbearing age must have a negative beta-HCG pregnancy test. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on specific inclusion criteria, ensuring that participants are registered with a social security scheme or a similar system. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the therapeutic efficacy of **filgrastim** in patients with severe bullous drug eruptions, specifically Lyell syndrome and Stevens-Johnson syndrome. This is a randomized, double-blind, controlled trial with an estimated duration extending until May 2026. The trial involves two arms: an experimental group receiving **filgrastim** in addition to standard symptomatic treatment, and a control group receiving only the standard symptomatic treatment combined with a placebo. The primary objective is to compare the cessation of disease progression after five days of treatment between the two groups.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, disease progression, and consent. The trial will include follow-up visits to monitor the treatment's effects and any adverse events. The end-of-study visit will assess the primary and secondary endpoints, including the halt in skin detachment progression, time to complete re-epidermalization, and overall survival rates at 30 and 365 days. The expected length of participant involvement is up to one year, with the possibility of early termination due to adverse events or other clinical considerations.

Inclusion criteria require participants to be six years or older, with a confirmed diagnosis of SJS or NET of drug or infectious origin, and disease progression observed within 48 hours. Exclusion criteria are not specified in the provided data. The trial will also evaluate secondary endpoints such as the number of hospital days, adverse events, and the use of systemic corticosteroid therapy. Participants' quality of life and the risk of developing post-traumatic stress disorder will be assessed. The trial aims to provide valuable insights into the efficacy of **filgrastim** in managing these severe conditions.

The clinical trial involves the administration of **Zarzio 30 MU/0.5 ml**, a **solution for injection or infusion** in a pre-filled syringe, containing the active substance **filgrastim**. Filgrastim is a protein-based therapeutic agent, specifically a recombinant form, used to stimulate the production of white blood cells. The pharmaceutical form is a solution for injection or infusion, and it is administered via injection. The maximum daily dose is 960 micrograms, with a total maximum dose of 4800 micrograms over a treatment period of 5 days. The product is manufactured by Sandoz GmbH and is not a pediatric formulation.

Another experimental treatment in the trial is **Zarzio 48 MU/0.5 ml**, also a **solution for injection or infusion** in a pre-filled syringe, containing the same active substance, **filgrastim**. This formulation is identical in pharmaceutical form and administration route to the Zarzio 30 MU/0.5 ml. The dosing schedule is consistent, with a maximum daily dose of 960 micrograms and a total maximum dose of 4800 micrograms over 5 days. This product is also produced by Sandoz GmbH and is not intended for pediatric use.

The trial includes a non-experimental treatment, **GLUCOSE FRESENIUS 5%**, a **solution for infusion** containing **glucose monohydrate**. This chemical-based solution is used as a placebo in the control group. The pharmaceutical form is a solution for infusion, administered via infusion. The maximum daily dose is 20 milliliters, with a total maximum dose of 100 milliliters over a 5-day treatment period. This product is manufactured by Fresenius Kabi France S.A.S. and is not a pediatric formulation.

The clinical trial aims to evaluate the therapeutic efficacy of **filgrastim** in patients with severe bullous drug eruptions, specifically Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (NET). The primary endpoint for assessing efficacy is the comparison between the experimental group receiving filgrastim and the control group receiving placebo, in terms of the proportion of patients experiencing a halt in the progression of skin detachment by Day 5. This is defined by the assessment of detached and/or bullous surface areas and the presence of a NIKOLSKY sign, determined according to the stable burns table.

Secondary endpoints include several parameters: time to stop progression, time to complete re-epidermalization, overall survival at Day 30 and Day 365, and the number of hospital days related to the SJS/NET episode. Additionally, the trial will monitor the number and nature of clinical or biological adverse events leading to premature discontinuation of filgrastim treatment between Day 0 and Day 5, as well as up to Day 365. The use of systemic corticosteroid therapy between Day 0 and Day 15 will be analyzed, including the nature, cumulative doses, and indications for prescriptions, with a comparison between the two treatment groups. Other assessments include the presence of sequelae in various medical domains, patient quality of life, and the risk of developing post-traumatic stress disorder (PTSD).