Clinical trial • Phase II/III • Dermatology

FILGRASTIM for Toxic epidermal necrolysis (Lyell syndrome) | Stevens-Johnson syndrome

Phase II/III trial of FILGRASTIM for Toxic epidermal necrolysis (Lyell syndrome) | Stevens-Johnson syndrome.

Overview

Trial Therapeutic Area
Dermatology
Trial Disease
Toxic epidermal necrolysis (Lyell syndrome) | Stevens-Johnson syndrome
Trial Stage
Phase II/III
Drug Modality
Peptide/protein/enzyme | Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
01-08-2024
First CTIS Authorization Date
12-08-2024

Trial design

Randomised, filgrastim (zarzio 30 mu and zarzio 48 mu pre-filled syringes) given iv or sc daily for 5 consecutive days (weight-based dosing: 20 to <30 kg = 0.3 ml zarzio 48 mu/0.5 ml sc; 30 to <60 kg = 0.5 ml zarzio 30 mu/0.5 ml iv; 60 to <90 kg = 0.5 ml zarzio 48 mu/0.5 ml iv; 90 to <120 kg = 2 x 0.5 ml zarzio 30 mu/0.5 ml iv; 120 to 150 kg = 0.5 ml zarzio 30 mu + 0.5 ml zarzio 48 mu iv; >150 kg = 2 x 0.5 ml zarzio 48 mu iv) versus placebo (glucose fresenius 5% 20 ml iv infusion once daily for 5 consecutive days). note: placebo is not available for 20 to <30 kg because the blinded injection must be subcutaneous.-controlled Phase II/III trial in France.

Randomised
Yes
Comparator
FILGRASTIM (Zarzio 30 MU and Zarzio 48 MU pre-filled syringes) given IV or SC daily for 5 consecutive days (weight-based dosing: 20 to <30 kg = 0.3 mL Zarzio 48 MU/0.5 mL SC; 30 to <60 kg = 0.5 mL Zarzio 30 MU/0.5 mL IV; 60 to <90 kg = 0.5 mL Zarzio 48 MU/0.5 mL IV; 90 to <120 kg = 2 x 0.5 mL Zarzio 30 MU/0.5 mL IV; 120 to 150 kg = 0.5 mL Zarzio 30 MU + 0.5 mL Zarzio 48 MU IV; >150 kg = 2 x 0.5 mL Zarzio 48 MU IV) versus PLACEBO (Glucose Fresenius 5% 20 mL IV infusion once daily for 5 consecutive days). Note: placebo is not available for 20 to <30 kg because the blinded injection must be subcutaneous.
Target Sample Size
42
Trial Duration For Participant
365

Eligibility

Recruits 42 paediatric patients.

Pregnancy Exclusion
Pregnant or breast-feeding women
Vulnerable Population
Includes minors (patients from 6 years of age and older). Consent must be given in writing by parents for minors; guardians may provide consent for patients in immediate life‑threatening situations. Subject information and consent forms exist for children 6–11 years and 12–17 years, for parents of minors (separate versions for children ≥30 kg and <30 kg), for minors becoming adult, and for adult patients; patients under protective measures (safeguard, curatorship, guardianship) or deprived of liberty are explicitly excluded.

Inclusion criteria

  • {"criterion_text":"- Patient 6 years of age and older, presenting with SJS or NET of proven or very strongly suspected (indirect argument of certainty) drug or infectious origin, confirmed by the evaluator"}
  • {"criterion_text":"- SJS or NET evolving for less than 7 days and with progression of the detachment or rash observed within 48 hours"}
  • {"criterion_text":"- Patient and/or guardians capable of understanding the objectives of the trial and having given written consent to participate (parents for minors, guardians for patients in immediate life-threatening situations)"}
  • {"criterion_text":"- Patient registered with a social security scheme or benefiting from a similar scheme"}
  • {"criterion_text":"- Negative beta-HCG pregnancy test for women of childbearing age"}

Exclusion criteria

  • {"criterion_text":"- Patients weighing less than 20 kg"}
  • {"criterion_text":"- Known hypersensitivity to the active substance (FILGRASTIM) or to the one of the excipients (glutamine acid, sorbitol E420, Polysorbate 80)"}
  • {"criterion_text":"- Patients with known glucose intolerance or hereditary fructose intolerance"}
  • {"criterion_text":"- Patient with a traumatic brain injury less than 24 hours"}
  • {"criterion_text":"- Patients in septic shock"}
  • {"criterion_text":"- Chronic myeloid disease such as myeloid leukemia or AML"}
  • {"criterion_text":"- Thrombophilia or current thrombosis pathology"}
  • {"criterion_text":"- PNN (polymorphonuclear neutrophils) > 50.000 on the CBC (Complete Blood Count) during the inclusion visit"}
  • {"criterion_text":"- Administration of G-CSF or GM-CSF within 5 days of inclusion"}
  • {"criterion_text":"- Patient who received cyclosporine, anti-TNFalpha or intravenous immunoglobulins or lithium in the month prior the inclusion"}
  • {"criterion_text":"- Pregnant or breast-feeding women"}
  • {"criterion_text":"- Patient under protective measure (safeguard measure, curatorship, guardianship) or deprived of liberty"}
  • {"criterion_text":"- Patient in exclusion period after participation at other interventional clinical trial"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Comparison between the 2 groups of the proportion of patients with a halt in the progression of skin detachment at D5 (D0: initiation of treatment) defined by a detached and/or bullous surface and/or associated with a NIKOLSKY sign determined according to the stable burns table","definition_or_measurement_approach":"Proportion of patients at Day 5 (from treatment initiation) with cessation of progression of skin detachment, defined by detached and/or bullous surface and/or presence of a Nikolsky sign; assessment determined according to the stable burns table."}

Secondary endpoints

  • {"endpoint_text":"- Time to stop progression","definition_or_measurement_approach":"Time from treatment initiation to cessation of disease progression."}
  • {"endpoint_text":"- Time to complete re-epidermalization, defined as disappearance of skin erosions AND return to normal skin","definition_or_measurement_approach":"Time from treatment initiation to complete re-epidermalization, operationally defined as disappearance of skin erosions and return to normal skin."}
  • {"endpoint_text":"- Overall survival at D30","definition_or_measurement_approach":"All-cause survival status assessed at Day 30."}
  • {"endpoint_text":"- Overall survival to D365","definition_or_measurement_approach":"All-cause survival status assessed up to Day 365."}
  • {"endpoint_text":"- Number of hospital days corresponding to the length of hospitalization for the SJS/NET episode","definition_or_measurement_approach":"Number of inpatient days attributable to the SJS/NET episode."}
  • {"endpoint_text":"- Number per patient and nature of clinical or biological adverse events observed between D0 and D5 leading to premature discontinuation of filgrastim treatment","definition_or_measurement_approach":"Count and characterization of clinical/biological adverse events between Day 0 and Day 5 that lead to premature discontinuation of filgrastim."}
  • {"endpoint_text":"- Total number per patient and nature of clinical or biological adverse events observed up to D365","definition_or_measurement_approach":"Total count and nature of adverse events per patient observed through Day 365."}
  • {"endpoint_text":"- Use of systemic corticosteroid therapy between D0 and D15, with a study of the nature, cumulative doses and indications for objective prescriptions. A comparison will be made between the 2 treatment groups.","definition_or_measurement_approach":"Assessment of systemic corticosteroid use between Day 0 and Day 15 including nature, cumulative doses and indications; between-group comparison."}
  • {"endpoint_text":"- Presence of ophthalmological, stomatological/ORL, gastroenterological, gynecological, urological and psychiatric sequelae","definition_or_measurement_approach":"Assessment (presence/absence) of listed organ-specific sequelae during follow-up."}
  • {"endpoint_text":"- Patient quality of life","definition_or_measurement_approach":"Quality of life assessment (instrument not specified in Part I data)."}
  • {"endpoint_text":"- Risk of developing post-traumatic stress disorder (PTSD)","definition_or_measurement_approach":"Assessment of risk or incidence of PTSD (assessment instrument/timing not specified in Part I data)."}

Recruitment

Planned Sample Size
42
Recruitment Window Months
20
Consent Approach
Written informed consent required. Adult patients provide consent themselves. For minors, parents must provide written consent; guardians can consent for patients in immediate life‑threatening situations. Subject information and consent forms exist in multiple age-specific versions (child 6–11 years, child 12–17 years, parent versions for minors ≥30 kg and <30 kg, minor becoming adult, adult patient, continuation after emergency), indicating age-appropriate information and assent/consent handling.

Geography

Total Number Of Sites
4
Total Number Of Participants
42

France

Earliest CTIS Part Ii Submission Date
07-08-2024
Latest Decision Or Authorization Date
27-06-2025
Processing Time Days
324
Number Of Sites
4
Number Of Participants
42

Sites

Site Name
Hospices Civils De Lyon
Department Name
Service de Médecine Interne (Pav O)
Principal Investigator Name
Solène POUTREL
Principal Investigator Email
solene.poutrel@chu-lyon.fr
Contact Person Name
Solène POUTREL
Contact Person Email
solene.poutrel@chu-lyon.fr
Site Name
Hospices Civils De Lyon
Department Name
Département Anesthésie-Réanimation rassemblant le Service de réanimation et des Brulés (Pav I), le
Principal Investigator Name
Anne-Claire LUKASZEWICZ
Principal Investigator Email
anne-claire.lukaszewicz@chu-lyon.fr
Contact Person Name
Anne-Claire LUKASZEWICZ
Site Name
Hospices Civils De Lyon
Department Name
Centre de référence sur les dermatoses bulleuses toxiques et les toxidermies sévères - Pavillon R
Principal Investigator Name
Benoit BEN SAID
Principal Investigator Email
benoit.ben-said@chu-lyon.fr
Contact Person Name
Benoit BEN SAID
Contact Person Email
benoit.ben-said@chu-lyon.fr
Site Name
Hospices Civils De Lyon
Department Name
Services d'Anesthésie-Réanimation (Pav I, Pav G) et unités de soins continus (USC, Pav I et H)
Principal Investigator Name
Véronique LERAY
Principal Investigator Email
veronique.leray@chu-lyon.fr
Contact Person Name
Véronique LERAY
Contact Person Email
veronique.leray@chu-lyon.fr

Sponsor

Primary sponsor

Full Name
Hospices Civils De Lyon
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Third parties

  • {"country":"France","full_name":"Direction Générale de l'Offre de Soins - France","duties_or_roles":"Source of monetary support","organisation_type":""}

Investigational products

Investigational Product Name
Zarzio 48 MU/0.5 ml solution for injection or infusion in pre-filled syringe
Active Substance
FILGRASTIM
Modality
Peptide/protein/enzyme
Routes Of Administration
INJECTION (SC or IV depending on weight)
Route
SC or IV depending on weight
Authorisation Status
Authorised
Starting Dose
Used in weight-based dosing per protocol: 20 to <30 kg = 0.3 mL of Zarzio 48 MU/0.5 mL (subcutaneous); 60 to <90 kg = 0.5 mL Zarzio 48 MU/0.5 mL (IV); 120 to 150 kg includes 0.5 mL Zarzio 48 MU (IV); >150 kg = 2 x 0.5 mL Zarzio 48 MU (IV).
Dose Levels
0.3 mL (48 MU) ; 0.5 mL (48 MU) ; 2 x 0.5 mL (48 MU)
Frequency
Once daily for 5 consecutive days
Maximum Dose
960 µg/day; 4800 µg total
Investigational Product Name
Zarzio 30 MU/0.5 ml solution for injection or infusion in pre-filled syringe
Active Substance
FILGRASTIM
Modality
Peptide/protein/enzyme
Routes Of Administration
INJECTION (IV or SC depending on weight)
Route
IV (some SC use may apply for certain weights)
Authorisation Status
Authorised
Starting Dose
Used in weight-based dosing per protocol: 30 to <60 kg = 0.5 mL Zarzio 30 MU/0.5 mL (IV); 90 to <120 kg = 2 x 0.5 mL Zarzio 30 MU/0.5 mL (IV); 120 to 150 kg includes 0.5 mL Zarzio 30 MU (IV).
Dose Levels
0.5 mL (30 MU) ; 2 x 0.5 mL (30 MU)
Frequency
Once daily for 5 consecutive days
Maximum Dose
960 µg/day; 4800 µg total
Investigational Product Name
GLUCOSE FRESENIUS 5 %, solution pour perfusion
Active Substance
GLUCOSE MONOHYDRATE
Modality
Small molecule
Routes Of Administration
INFUSION (IV)
Route
IV infusion
Authorisation Status
Authorised
Starting Dose
20 mL of Glucose 5% solution IV once daily for 5 consecutive days (placebo comparator). Note: placebo not available for 20 to <30 kg since the blinded injection would need to be SC.
Dose Levels
20 mL IV
Frequency
Once daily for 5 consecutive days
Maximum Dose
20 mL/day; 100 mL total
Combination Treatment
Yes

Related trials

Other published trials that may interest you.