NCT04651439

Severe Bullous Drug Eruption and Filgrastim

Evaluating the Therapeutic Efficacy of Filgrastim in Severe Bullous Drug Eruptions (Lyell and Stevens-Johnson Syndromes)

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: Hospices Civils de Lyon · Academic / Other
• Sex: All
• Age: 6 Years
• Healthy volunteers: Not accepted

Summary

Toxic epidermal necrolysis (TEN) including Stevens Johnson (SJS) and Lyell syndromes represent the most severe drug eruptions. It is an allergic disorder caused by cytotoxic T lymphocytes, specific of drugs, responsible for the destruction of keratinocytes by apoptosis. Regulatory T cell (CD25 high CD4+), normally responsible for controlling the activation of cytotoxic T lymphocytes, have altered function. Despite the progress made in the pathophysiological understanding of TEN, there is currently no effective treatment. The main symptom is bullous and skin peeling \> 10% giving the appearance of great burns. The death rate is estimated between 30 and 40% due to visceral inflammatory injuries and bacterial superinfection. The risk of mortality is estimated during the initial treatment by calculating the SCORTEN (mortality\>10% if SCORTEN\>2, mortality\>90% if SCORTEN\>5). The morbidity is also very important (92% at 1 year), especially ophthalmologic with high risk of blindness... The therapeutic potential of G-CSF (Granulocyte-Colony Stimulating Factor) in TEN is supported by several observations. The G-CSF promotes skin healing. This has been shown in human burns, with a significant reduction in healing time under G-CSF. The mechanisms associate the growth factor effect on keratinocytes, macrophages stimulation and metalloprotease activity allowing tissue remodeling limiting sequels onset. Otherwise, healing altered in deficient G-CSF mice is corrected by the growth factor injection. The G-CSF is an immunomodulator whose activities appear to justify use in TEN : * Polarization of immune response to Th2 non-cytotoxic (anti Th1), * Preferential differentiation of naive LT (T lymphocytes) in regulator LT (CD25 high CD4+) and mobilization of regulator LT of the spinal cord to altered tissues. The G-CSF was used in a few cases of TEN with great efficacy. No data is available concerning sequels of SJS/TEN in treated patients. This clinical trial program, by providing proof of the efficacy of filgrastim in SJS/TEN, should allow progress in care of this serious toxics diseases. In the future, it could thus reduce the significant morbidity of these syndromes with a high rate of sequelae.

Conditions

• Rare Diseases
• Toxic Epidermal Necrolyses

Interventions

Type	Name	Description
DRUG	Filgrastim	Injection of ZARZIO 30 MU/0,5mL and/or ZARZIO 48 MU/0,5mL, over a period of 5 consecutive days (1 injection per day during 30 minutes - - day 1 : set up standard treatment). The filgrastim solution will be diluted in 20 mL of 5% Glucose. The dose of ZARZIO administrated depends of the patient's weight : * 20 to \< 30kg = 0,3 mL of ZARZIO 48 MU/0,5mL (subcutaneous route) * 30 to \< 60kg = 0,5 mL of ZARZIO 30 MU/0,5mL (by IV) * 60 to \< 90kg = 0,5 mL of ZARZIO 48 MU/0,5mL (by IV) * 90 to \< 120kg = 2x0,5 mL of ZARZIO 30 MU/0,5mL (by IV) * 120 to 150kg = 0,5 mL of ZARZIO 30 MU/0,5mL + 0,5 mL of ZARZIO 48 MU/0,5mL (by IV) * \> 150kg = 2x0,5 mL of ZARZIO 48 MU/0,5mL (by IV)
DRUG	Placebo	Injection of 20 mL of Glucose 5% solution over a period of 5 consecutive days (1 injection per day during 30 minutes - day 1 : set up standard treatment). The dose given is equivalent to that used for filgrastim : * 20 to \< 30kg = placebo not available because the injection must be done subcutaneously so the blind cannot be respected. * 30 to \< 60kg = 20mL of Glucose 5% solution (by IV) * 60 to \< 90kg = 20mL of Glucose 5% solution (by IV) * 90 to \< 120kg = 20mL of Glucose 5% solution (by IV) * 120 to 150kg = 20mL of Glucose 5% solution (by IV) * \> 150kg = 20mL of Glucose 5% solution (by IV)

Timeline

• Start date: 2022-05-13
• Primary completion: 2025-05-18
• Completion: 2026-05-13
• First posted: 2020-12-03
• Last updated: 2024-05-08

Locations

3 sites across 1 country: France