Overview
Sponsor-declared trial summary
Phase
Phase II and Phase III (Integrated)
Status
Ongoing, recruiting
Participants planned
42
Countries
1
Sites
4
Lyell syndrome
Compare, after 5 days of treatment, the cessation of disease progression in patients with SJS/NET between 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 …
Key facts
- Sponsor
- Hospices Civils De Lyon
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Trial duration
- 13 May 2022 → ongoing
- Decision date (initial)
- 2024-08-12
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Direction Générale de l'Offre de Soins - France
External identifiers
- EU CT number
- 2024-515275-35-00
- EudraCT number
- 2020-003544-83
- ClinicalTrials.gov
- NCT04651439
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety, Efficacy
Compare, after 5 days of treatment, the cessation of disease progression in patients with SJS/NET between 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).
Secondary objectives 11
- 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 FILGRASTIM and CONTROL treatment arms
- Evaluation of overall survival at time D30 between FILGRASTIM and CONTROL treatment arms
- Evaluation of overall survival to 365 days between FILGRASTIM and CONTROL arms
- Evaluation of the number of days of hospitalization corresponding to the SJS/NET episode between the FILGRASTIM and CONTROL 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 risk of developing post-traumatic stress disorder (PTSD)
Conditions and MedDRA coding
Lyell syndrome
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | LLT | 10042030 | Stevens Johnson syndrome | 10040785 |
| 20.0 | LLT | 10025166 | Lyell syndrome | 10040785 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Filgrastim (ZARZIO) / Placebo (Glucose 5%) Single-center, randomized, controlled, single-blind (patient) versus placebo, clinical phase 2/3, superiority pilot trial comparing two therapeutic strategies:
- FILGRASTIM EXPERIMENTAL arm: reference symptomatic treatment combined with intravenous or subcutaneous ZARZIO treatment,
- CONTROL arm: reference symptomatic treatment combined with intravenous placebo (5% glucose) (except for patients weighing less than 30kg).
|
Randomised Controlled | Single | [{"id":131952,"code":1,"name":"Subject"}] | 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) 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) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- 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
- SJS or NET evolving for less than 7 days and with progression of the detachment or rash observed within 48 hours
- 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)
- Patient registered with a social security scheme or benefiting from a similar scheme
- Negative beta-HCG pregnancy test for women of childbearing age
Exclusion criteria 13
- Patients weighing less than 20 kg
- Chronic myeloid disease such as myeloid leukemia or AML
- Thrombophilia or current thrombosis pathology
- PNN (polymorphonuclear neutrophils) > 50.000 on the CBC (Complete Blood Count) during the inclusion visit
- Administration of G-CSF or GM-CSF within 5 days of inclusion
- Patient who received cyclosporine, anti-TNFalpha or intravenous immunoglobulins or lithium in the month prior the inclusion
- Pregnant or breast-feeding women
- Patient under protective measure (safeguard measure, curatorship, guardianship) or deprived of liberty
- Patient in exclusion period after participation at other interventional clinical trial
- Known hypersensitivity to the active substance (FILGRASTIM) or to the one of the excipients (glutamine acid, sorbitol E420, Polysorbate 80)
- Patients with known glucose intolerance or hereditary fructose intolerance
- Patient with a traumatic brain injury less than 24 hours
- Patients in septic shock
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 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
Secondary endpoints 11
- Time to stop progression
- Time to complete re-epidermalization, defined as disappearance of skin erosions AND return to normal skin
- Overall survival at D30
- Overall survival to D365
- Number of hospital days corresponding to the length of hospitalization for the SJS/NET episode
- Number per patient and nature of clinical or biological adverse events observed between D0 and D5 leading to premature discontinuation of filgrastim treatment
- Total number per patient and nature of clinical or biological adverse events observed up to D365
- 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.
- Presence of ophthalmological, stomatological/ORL, gastroenterological, gynecological, urological and psychiatric sequelae
- Patient quality of life
- Risk of developing post-traumatic stress disorder (PTSD)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Zarzio 48 MU/0.5 ml solution for injection or infusion in pre-filled syringe
PRD6059198 · Product
- Active substance
- Filgrastim
- Substance synonyms
- NT100H, FILGRASTIM (GENETICAL RECOMBINATION)
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INJECTION
- Max daily dose
- 960 µg microgram(s)
- Max total dose
- 4800 µg microgram(s)
- Max treatment duration
- 5 Day(s)
- Authorisation status
- Authorised
- ATC code
- L03AA02 — FILGRASTIM
- Marketing authorisation
- EU/1/08/495/005
- MA holder
- SANDOZ GMBH
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Zarzio 30 MU/0.5 ml solution for injection or infusion in pre-filled syringe
PRD6061083 · Product
- Active substance
- Filgrastim
- Substance synonyms
- NT100H, FILGRASTIM (GENETICAL RECOMBINATION)
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INJECTION
- Max daily dose
- 960 µg microgram(s)
- Max total dose
- 4800 µg microgram(s)
- Max treatment duration
- 5 Week(s)
- Authorisation status
- Authorised
- ATC code
- L03AA02 — FILGRASTIM
- Marketing authorisation
- EU/1/08/495/001
- MA holder
- SANDOZ GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
GLUCOSE FRESENIUS 5 %, solution pour perfusion
PRD778182 · Product
- Active substance
- Glucose Monohydrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INFUSION
- Max daily dose
- 20 ml millilitre(s)
- Max total dose
- 100 ml millilitre(s)
- Max treatment duration
- 5 Day(s)
- Authorisation status
- Authorised
- ATC code
- B05BA03 — CARBOHYDRATES
- Marketing authorisation
- 34009 367 626 4 0
- MA holder
- FRESENIUS KABI FRANCE S.A.S.
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Hospices Civils De Lyon
- Sponsor organisation
- Hospices Civils De Lyon
- Address
- 3 Quai Des Celestins, Bp 2251 Bp 2251
- City
- Lyon Cedex 02
- Postcode
- 69229
- Country
- France
Scientific contact point
- Organisation
- Hospices Civils De Lyon
- Contact name
- Benoît BEN SAID
Public contact point
- Organisation
- Hospices Civils De Lyon
- Contact name
- Benoît BEN SAID
Locations
1 EU/EEA country · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 42 | 4 |
| Rest of world | — | 0 | — |
Investigational sites
Hospices Civils De Lyon
Centre de référence sur les dermatoses bulleuses toxiques et les toxidermies sévères - Pavillon R, 5 Place D Arsonval, 69437, Lyon Cedex 03
Hospices Civils De Lyon
Service de Médecine Interne (Pav O), 5 Place D Arsonval, 69437, Lyon Cedex 03
Hospices Civils De Lyon
Services d'Anesthésie-Réanimation (Pav I, Pav G) et unités de soins continus (USC, Pav I et H), 5 Place D Arsonval, 69437, Lyon Cedex 03
Hospices Civils De Lyon
Département Anesthésie-Réanimation rassemblant le Service de réanimation et des Brulés (Pav I), le, 5 Place D Arsonval, 69437, Lyon Cedex 03
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2022-05-13 | 2022-05-13 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 14 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-515275-35-00 | 8 |
| Protocol (for publication) | D1_Protocol 2024-515275-35-00 | 8.1 |
| Recruitment arrangements (for publication) | K1_Document additionnel | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and CF Enfant de 12 a 17 ans | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and CF Enfant de 6 a 11 ans | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and CF Mineur devenant majeur | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and CF Parent enfant mineur 30kg ou plus | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and CF Parent enfant mineur moins de 30 kg | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and CF Patient majeur | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and CF Patient poursuite apres situation durgence | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and CF Representant patient | 4 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC ZARZIO | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC ZARZIO | 1 |
| Synopsis of the protocol (for publication) | D1_protocol-synopsis-FR 2024-515275-35-00 | 8 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-08-01 | France | Acceptable 2024-08-09
|
2024-08-12 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-04-30 | France | Acceptable 2025-06-27
|
2025-06-27 |