LYell SYndrome MEsenchymal Stromal Cells Treatment

NCT04711200 | Recruiting Phase 1 DMC

• 2 other identifiers: P150941J2024-516404-42-00
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions (SCARs) to drugs. To date, no curative drug has demonstrated with a good level of evidence its ability to promote SJS and TEN healing and could contribute to earlier reepithelialisation. Mesenchymal stroma cells (MSCs) therapy represents a new therapeutic approach. eg, in patients with cardiovascular diseases, neurological diseases, renal transplantation, lung diseases as acute respiratory distress syndrome. Recently, MSCs have been proposed in both burn wound healing with a significantly decrease of the unhealed burn area and in cutaneous radiation. Moreover, MSCs have immunomodulation properties potentially effective in refractory acute and chronic graft versus host disease (GVHD) by improving thymic function and induction of Tregs. Indeed, MSCs are able to migrate to inflamed tissues after stimulation by pro-inflammatory cytokines and to modulate the local inflammatory reactions. MSCs have also demonstrated their ability to promote tissue remodelling, angiogenesis and immunomodulation through either differentiation or secretion of several growth factors such as VEGF, basic FGF and various cytokines. Therefore, combining their immunomodulation effect and secretion of soluble factors involved in wound repair, MSCs might be valuable as a cell therapy strategy for promoting cutaneous healing in SJS-TEN syndrome and subsequently decrease the morbi-mortality.

Conditions

Epidermal Necrolysis; Lyell Syndrome; Toxic Epidermal Necrolysis; Overlap Syndrome; Mesenchymal Stromal Cells; Adipose Derived Stromal Cells

Keywords

Epidermal necrolysis; Lyell syndrome; toxic epidermal necrolysis; Overlap syndrome; Mesenchymal stromal cells; Adipose derived stromal cells

Outcome Measures

Primary Outcomes (2)

• Safety : Observation of at least one adverse effect

  Day 10

• Efficacy : Rate of complete or almost complete reepithelialisation

  Day 7 after infusion

Secondary Outcomes (12)

• Rate of observed and predicted death by the SCORTEN

  at one month

• Duration of hospitalisation according to our historical cohort related to BSA involved

  Month 12

• Duration of hospitalisation according to our historical cohort related to onset of the disease

  Month 12

• Duration of hospitalisation according to our historical cohort related to SCORTEN

  Month 12

• Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes)

  at Month 12

Study Arms (1)

Adipose derived stromal cells intravenously injected

EXPERIMENTAL

Drug: Adipose derived stromal cells intravenously injected

Interventions

Adipose derived stromal cells intravenously injected DRUG

2×10\^6/kg of Adipose derived stromal cells A single injection at D0 (performed maximum three days post-admission).

Adipose derived stromal cells intravenously injected

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 and ≤ 75 years-old
• Admission ≤ 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)
• Who, after the nature of the study has been explained to them or a support person (if applicable), and prior to any protocol specific procedures being performed, have given written consent according to local regulatory requirements
• Affiliated to a social security scheme

You may not qualify if:

• 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
• Detection of Coronavirus SARS CoV-2 RNA on admission (positive RT-PCR), if performed in the usual care
• Decompensated cardiac failure
• Uncontrolled epilepsia
• Previous history of allogenic bone marrow transplantation
• Participation in other interventional drug research Patient deprived of liberty by a judicial or administrative decision or under the protection of justice
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the research protocol and follow-up schedule
• Patient under tutorship or curatorship
• Patient under psychiatric care according to art. L1121-6 CSP

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Henri Mondor

Créteil, France

RECRUITING

Related Publications (5)

• Duong TA, Valeyrie-Allanore L, Wolkenstein P, Chosidow O. Severe cutaneous adverse reactions to drugs. Lancet. 2017 Oct 28;390(10106):1996-2011. doi: 10.1016/S0140-6736(16)30378-6. Epub 2017 May 2.

  PMID: 28476287 BACKGROUND

• Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes Bavinck JN, Sidoroff A, Schneck J, Roujeau JC, Flahault A. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008 Jan;128(1):35-44. doi: 10.1038/sj.jid.5701033. Epub 2007 Sep 6.

  PMID: 17805350 BACKGROUND

• Creamer D, Walsh SA, Dziewulski P, Exton LS, Lee HY, Dart JK, Setterfield J, Bunker CB, Ardern-Jones MR, Watson KM, Wong GA, Philippidou M, Vercueil A, Martin RV, Williams G, Shah M, Brown D, Williams P, Mohd Mustapa MF, Smith CH. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol. 2016 Jun;174(6):1194-227. doi: 10.1111/bjd.14530. No abstract available.

  PMID: 27317286 BACKGROUND

• Roux S, Leotot J, Chevallier N, Bierling P, Rouard H. [Mesenchymal stromal cells: Biological properties and clinical prospects]. Transfus Clin Biol. 2011 Feb;18(1):1-12. doi: 10.1016/j.tracli.2011.01.001. Epub 2011 Mar 1. French.

  PMID: 21367635 BACKGROUND

• Chung HM, Won CH, Sung JH. Responses of adipose-derived stem cells during hypoxia: enhanced skin-regenerative potential. Expert Opin Biol Ther. 2009 Dec;9(12):1499-508. doi: 10.1517/14712590903307362.

  PMID: 19780713 BACKGROUND

MeSH Terms

Conditions

Stevens-Johnson Syndrome

Condition Hierarchy (Ancestors)

Stomatitis; Mouth Diseases; Stomatognathic Diseases; Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Erythema Multiforme; Erythema; Skin Diseases, Vesiculobullous; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Study Officials

• Saskia Oro, PhD

  saskia.oro@aphp.fr

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Saskia Oro, MD

CONTACT

0149812536; saskia.oro@aphp.fr

Charline Menanteau, MSc

CONTACT

0144841752; myriem.carrier@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: January 15, 2021
• Study Start: April 15, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)