NCT04651439: GNET

Severe Bullous Drug Eruption and Filgrastim

Recruiting now Phase 2, PHASE3 Last updated 8 May 2024

What this trial tests

Phase 2, PHASE3 trial testing Filgrastim in Rare Diseases in 42 participants. Currently enrolling.

Timeline

13 May 2022

Primary endpoint
18 May 2025

13 May 2026

Quick facts

Lead sponsor	Hospices Civils de Lyon
Phase	Phase 2, PHASE3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	42
Start date	13 May 2022
Primary completion	18 May 2025
Estimated completion	13 May 2026
Sites	3 locations across France

Drugs / interventions tested

• Filgrastim — full drug profile →
• Placebo

Conditions studied

• Rare Diseases — all drugs for Rare Diseases →
• Toxic Epidermal Necrolyses — all drugs for Toxic Epidermal Necrolyses →

Sponsor

Hospices Civils de Lyon — full company profile →

Who can join

6 and older, any sex, with Rare Diseases or Toxic Epidermal Necrolyses. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Scoring Assessments in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.
   Dobry AS, Himed S, Waters M, Kaffenberger BH. · · 2022 · cited 18× · PMID 35783656 · DOI 10.3389/fmed.2022.883121