LYell SYndrome MEsenchymal Stromal Cells Treatment

Official title

Mesenchymal Stromal Cells Treatment in Lyell Syndrome: A Pilot Phase 1-2 Open Trial

Overview

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.

Interventions

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

Primary outcome measures

• Safety : Observation of at least one adverse effect [Time frame: Day 10]
• Efficacy : Rate of complete or almost complete reepithelialisation [Time frame: Day 7 after infusion]

Secondary outcome measures (12)

• Rate of observed and predicted death by the SCORTEN [Time frame: at one month]
• Duration of hospitalisation according to our historical cohort related to BSA involved [Time frame: Month 12]
• Duration of hospitalisation according to our historical cohort related to onset of the disease [Time frame: Month 12]
• Duration of hospitalisation according to our historical cohort related to SCORTEN [Time frame: Month 12]
• Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes) [Time frame: at Month 12]
• Rate of sepsis [Time frame: at Month 12]
• Rate of intensive care transfer [Time frame: at Month 12]
• Rate of sequelae [Time frame: at Month 12]
• Th1/Th2 immune response in the peripheral blood of the patients [Time frame: after injection at Day 0, Day 10, Month 1]
• Evaluation of expression profile of Th1/Th2 associated chemokines and anti-inflammatory chemokines in the peripheral blood [Time frame: after injection at Day 0, Day 10, Month 1.]
• Epidermal chimerism study on healed skin biopsy [Time frame: 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. [Time frame: at Day 5, Day 10 and Day15]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Henri Mondor — Créteil

Publications

• 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
• 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 PMID 27317286
• 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
• 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
• 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

Identifiers

NCT: NCT04711200 · P150941J · 2024-516404-42-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗