Patients: Adults diagnosed with SJS-TEN with at least 10% of body surface area involved. MedDRA version: 20.0 Level: LLT Classification code 10025166 Term: Lyell syndrome System Organ Class: 100000004858
Conditions
Interventions
Product Name: expanded allogeneic adipose derived stromal cells
Pharmaceutical Form: Suspension for injection
Sponsors
ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients: - Patients aged from 18 to 75 years-old - Admission less than 10 days after the index date (date of the first symptoms of the disease) - Patient with confirmed SJS-TEN diagnosis hospitalized in the department of Dermatology or intensive care medicine - At least 10 % of detachable-detached body surface area at any time during the first 10 days after the index date (date of the first symptoms of the disease) - Written consent from patient or trustworthy person or legal representant or family member - Affiliated to a social security scheme Donors: - Donors aged from 18 to 55 years old - Admission for a programmed plastic surgery of liposuction or aspiration in the abdominal wall under general anesthesia - Selection criteria according to stem cell donor health history questionnaire from Agence de la Biomédecine - Written consent - Affiliated to a social security scheme Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Patients: - Pregnant or breastfeeding women - History of malignant disease within the past ten years and or presence of metastasis - Positive serology for HIV - Active infection for hepatitis B or C - Decompensated cardiac failure - Uncontrolled epilepsia - Previous history or allogenic bone marrow transplantation - Participation in other interventional drug research - Patient deprived of freedom - Any psychological, familial, sociological or geographical condition potentially hampering compliance with the research protocol and follow-up schedule Donors: - Positive viral serology (HBV, HCV, HIV, HEV, syphilis, HTLV, active infection with IgM+ for toxoplasmosis, EBV, CMV) - Deprived of freedom - Significant comorbidities according to donor health history or authenticated risk factors for viral infections in the past 12 months: • Multiple sexual partners between the donor or his or her usual partner • Intravenous addiction to the donor or regular partner • Accident of exposure to blood or derivatives suspected of being contaminated - Treatment with extractive pituitary hormones (including growth hormones) - Human dura mater transplant - Surgical history of the central nervous system - Dementia or neurological disease that may evoke subacute spongiform encephalopathy - Family history as part of subacute spongiform encephalopathy - Hematological malignancies - Active or cured cancer - System disease - Active generalized infection (viral, parasitic, tuberculosis, leprosy...) - Multiple adenopathy, splenomegaly, hepatomegaly - Icterus - Chemotherapy history, irradiation - Long-term steroids ( > 90 days)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Safety : The toxicity is defined as the observation of at least one of the following adverse events: - Persisting fever (> 38.5°C between D5 and D10) independently of a sepsis - Local acute infusional toxicity: phlebitis, hematoma, local infection between D0 and D3 - Anaphylaxis or severe systemic reaction following ASCs administration at D0 - Rash between D0 and D3, involving =30% of BSA - Cardiac complications in absence of previous cardiologic disease between D0 and D3 - Sustained ventricular arrhythmia between D0 and D3 - ST-elevation myocardial infarction between D0 and D3 - Acute pulmonary edema with PaO2 25, laboured breathing, cyanosis, dyspnoea NYHA Grade IV) in absence of infectious pneumopathy and specific SJS-TEN lung involvement between D0 and D3 - Cardiogenic shock with signs of hypoperfusion between D0 and D3 - Thrombo-embolic event between D0 and D3 - Cerebral infarction between D0 and D3 - Acute renal failure or doubling of creatinine between D0 and D3 - Epilepsia between D0 and D3 - Sepsis between D0 and D3 - Death between D0 and D3 If one of these outcome is observed, then it will be considered as a toxicity for the patient. Efficacy: The efficacy is defined as the cutaneous re-epithelialization at D7 post-infusion according to the percentage of cutaneous BSA re-epithelialized in comparison to maximal cutaneous detachable-detached BSA observed previous or after infusion. Complete response, almost complete response : At least 90% of detached-detachable cutaneous BSA re-epithelialized. Partial response : Between 50% and 90% of detached-detachable cutaneous BSA re-epithelialized. Failure : Less than 50% of detached-detachable cutaneous BSA re-epithelialized. For simplicity, regarding the small sample size of the trial, complete (or almost complete) response and partial response will be considered as procedure success. In case of patient’s death, his(her) response will be considered as a failure of the procedure. Cutaneo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Rate of observed and predicted death at one month by the SCORTEN . - Duration of hospitalization according to historical cohort related to BSA involved, onset of the disease and SCORTEN. - Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes). - Rate of sepsis at one month. - Rate of intensive care transfer at one month. - Rate of sequelae at M12 - Th1/Th2 immune response in the peripheral blood of the patients before injection at D0, D7 and M1 - Evaluation of expression profile of Th1/Th2 associated chemokines and anti-inflammatory chemokines in the peripheral blood after injection at D0, D7 and M1. - Epidermal chimerism research on healed skin biopsy and peripheral blood at 1 month. - Cutaneous re-epithelialization rate at D5, D10 and D15 post-infusion according to the percentage of cutaneous BSA re-epithelialized in comparison to maximal cutaneous detachable-detached BSA observed.;Timepoint(s) of evaluation of this end point: 12 Month | — |
Countries
France
Outcome results
None listed