Clinical trial NCT04711200: LYell SYndrome MEsenchymal Stromal Cells Treatment
Official title: Mesenchymal Stromal Cells Treatment in Lyell Syndrome: A Pilot Phase 1-2 Open Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-01-15
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Patients aged from 18 to 75 years-old
* Admission less than 10 days after onset of the reaction
* 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

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
* 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

Primary outcomes:
measure: Safety : Observation of at least one adverse effect
timeFrame: Day 10
measure: Efficacy : Rate of complete or almost complete reepithelialisation
timeFrame: Day 7 after infusion
Secondary outcomes:
measure: Rate of observed and predicted death by the SCORTEN
timeFrame: at one month
measure: Duration of hospitalisation according to our historical cohort related to BSA involved
timeFrame: Month 12
measure: Duration of hospitalisation according to our historical cohort related to onset of the disease
timeFrame: Month 12
measure: Duration of hospitalisation according to our historical cohort related to SCORTEN
timeFrame: Month 12
measure: Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes)
timeFrame: at Month 12
measure: Rate of sepsis
timeFrame: at Month 12
measure: Rate of intensive care transfer
timeFrame: at Month 12
measure: Rate of sequelae
timeFrame: at Month 12
measure: Th1/Th2 immune response in the peripheral blood of the patients
timeFrame: after injection at Day 0, Day 10, Month 1
measure: Evaluation of expression profile of Th1/Th2 associated chemokines and anti-inflammatory chemokines in the peripheral blood
timeFrame: after injection at Day 0, Day 10, Month 1.
measure: Epidermal chimerism study on healed skin biopsy
timeFrame: at 1 month
measure: 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.
timeFrame: at Day 5, Day 10 and Day15
Other outcomes:
Locations:
Study officials:
affiliation: saskia.oro@aphp.fr
name: Saskia Oro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.