A Phase 2/3 interventional study of Filgrastim and Placebo in Rare Diseases and Toxic Epidermal Necrolyses, sponsored by Hospices Civils de Lyon. Recruiting at 3 sites in France. Open to participants aged 6 Years and older. Per ClinicalTrials.gov, last updated 2024-05-08.
Sponsored by Hospices Civils de Lyon · Phase 2/3, Interventional, and Treatment
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 :
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.
Exclusion Criteria:
Standard symptomatic treatment of the SJS/NET (until the reepidermization of the patient) + ZARZIO@ (30 MU/0,5mL and/or 48 MU/0,5mL - solution of 20 ml diluted in GLUCOSE 5%) administrated by IV or subcutaneous route over a period of 5 consecutive days (1 injection per day during 30 minutes)
Drug: Filgrastim
Standard symptomatic treatment of the SJS/NET (until the reepidermization of the patient) + 20 ml GLUCOSE 5% administrated by IV route over a period of 5 consecutive days (1 injection per day during 30 minutes)
Drug: Placebo
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)
Also known as: ZARZIO
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)
Also known as: GLUCOSE 5%
Arrest of the SJS/NET progression at day 5
Comparison between the 2 arms of the proportion of patients with arrest of progression of skin detachment defined by a peeled surface and/or bullous and/or associated at a NIKOLSKY sign determined according to the stable burn table - Evaluation done by the Outcomes Assessor and the adjudication committee.
Time frame: On day 5 (after 5 injections of ZARZIO or PLACEBO - D0: initiation of treatment)
Arrest of the SJS/NET progression
Comparison between the 2 arms of the time until the arrest of the SJS/NET progression defined by a peeled surface and/or bullous and/or associated at a NIKOLSKY sign determined according to the stable burn table - Evaluation done by the Outcomes Assessor and the adjudication committee.
Time frame: At day 3, day 7 and day 15
Complete re-epidermization
Comparison between the 2 arms of the time until the complete re-epidermization defined by the disappearance of skin rashes and return to normal skin. Evaluation done by the Outcomes Assessor and the adjudication committee.
Time frame: At day 3, day 5, day 7, day 15 and day 45
Overall survival
Comparison between the 2 arms of the overall survival
Time frame: Until 30 days
Overall survival
Comparison between the 2 arms of the overall survival
Time frame: Until 1 year
Duration of hospitalization
Comparison between the 2 arms of the number days of hospitalization corresponding to the duration of SJS/NET episode's hospitalization.
Time frame: 15 days (maximal of SJS/NET episode's hospitalization)
Premature discontinuation of experimental treatment
Number of clinical and biological adverse event leading to stop the filgrastim treatment (per patient, nature and grade of the AE (adverse event ) - repository CTCAE version 5.0)
Time frame: Between day 0 and day 5
Adverse events
Comparison between the 2 arms of the number of clinical and biological adverse event (by organ systems - repository CTCAE version 5.0)..
Time frame: Until 1 year
Use of systemic corticosteroid therapy
Study of the nature, cumulative doses and indications objectifying a corticosteroid prescription. A comparison between the 2 arms will be done.
Time frame: Between day 0 and day 15
Evaluation of sequels
Determination of the proportion of patients with at least one sequel among the following specialty : ophthalmology, stomatology/ORL(otorhinolaryngology), gastroenterology, gynecology, urology and psychiatry, researched during specialized consultations during the remote monitoring phase. A comparison between the 2 arms will be done.
Time frame: At day 45, day 60, day 90, day 180 and 1 year
Quality of life evolution
Quality of life evolution assessed with Dermatology Life Quality Index (DLQI) or Children's Dermatology Life Quality Index (CDLQI). DLQI is calculated by adding the score of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. CDLQI is used in the same way. It is documented in 5 minutes. Each question is illustrated by a cartoon based on the theme of the question, making it more fun for younger children. The scoring for each question is "Very much"\[Score = 3\], "Quite a lot"\[2\], "Only a little"\[1\], "Not at all"\[0\], "Blank"\[0\], and Q7 - "prevented school"\[3\]. The 10 individual question scores are summed to provide a total CDLQI score. The maximum possible score is 30, indicating maximum impact on QoL. A comparison between the 2 arms will be done.
Time frame: At day 60, day 180 and 1 year
Risk of developing Post Traumatic Stress Disorder (PTSD)
Determination of the proportion of patients with high risk of developing PTSD measured with Impact of Event Scale Revised (IES-R) or Children's Revised Impact of Event Scale (CRIES). IES-R is a 22-item self-administered questionnaire that measures symptoms of intrusion, avoidance and over-arousal experienced during the past 7 days. Patients rate each item on a 0-5 point Likert scale. The total score, between 0 and 88, is obtained by adding all the ratings for each item: low risk (score less than 12), moderate (score between 12 and 34 inclusive) or at high risk (score strictly greater than 34) of developing PTSD. CRIES-13 is a revised scale to measure the impact of events on children from 8 years old. Items are rated on a 4-point scale, with scores of 0, 1, 3 and 5 points. The maximum score is 65. The score is obtained by adding the responses to each item. A score of 30 or more would be effective in screening for PTSD. A comparison between the 2 arms will be done.
Time frame: At day 0, day 7 and day 15
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Hospices Civils de Lyon