LYell SYndrome MEsenchymal Stromal Cells Treatment

Mesenchymal Stromal Cells Clinical Trial

— LYSYME  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04711200
• Other study ID #: P150941J
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: September 2022
• Est. completion date: September 2025

Study information

• Verified date: April 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Saskia Oro, MD
• Phone: 0149812536
• Email: saskia.oro[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 15
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Adipose Derived Stromal Cells
• Epidermal Necrolysis
• Lyell Syndrome
• Mesenchymal Stromal Cells
• Overlap Syndrome
• Stevens-Johnson Syndrome
• Syndrome
• Toxic Epidermal Necrolysis

Intervention

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).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

References & Publications (5)

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. Review. — View 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. — View 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. Review. Erratum in: Lancet. 2017 Oct 28;390(10106):1948. — View 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. Epub 2007 Sep 6. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety : Observation of at least one adverse effect		Day 10
Primary	Efficacy : Rate of complete or almost complete reepithelialisation		Day 7 after infusion
Secondary	Rate of observed and predicted death by the SCORTEN		at one month
Secondary	Duration of hospitalisation according to our historical cohort related to BSA involved		Month 12
Secondary	Duration of hospitalisation according to our historical cohort related to onset of the disease		Month 12
Secondary	Duration of hospitalisation according to our historical cohort related to SCORTEN		Month 12
Secondary	Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes)		at Month 12
Secondary	Rate of sepsis		at Month 12
Secondary	Rate of intensive care transfer		at Month 12
Secondary	Rate of sequelae		at Month 12
Secondary	Th1/Th2 immune response in the peripheral blood of the patients		after injection at Day 0, Day 10, Month 1
Secondary	Evaluation of expression profile of Th1/Th2 associated chemokines and anti-inflammatory chemokines in the peripheral blood		after injection at Day 0, Day 10, Month 1.
Secondary	Epidermal chimerism study on healed skin biopsy		at 1 month
Secondary	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.		at Day 5, Day 10 and Day15