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LYell SYndrome MEsenchymal Stromal Cells Treatment (LYSYME)

Primary Purpose

Epidermal Necrolysis, Lyell Syndrome, Toxic Epidermal Necrolysis

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Adipose derived stromal cells intravenously injected
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epidermal Necrolysis focused on measuring Epidermal necrolysis, Lyell syndrome, toxic epidermal necrolysis, Overlap syndrome, Mesenchymal stromal cells, Adipose derived stromal cells

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Adipose derived stromal cells intravenously injected

    Arm Description

    Outcomes

    Primary Outcome Measures

    Safety : Observation of at least one adverse effect
    Efficacy : Rate of complete or almost complete reepithelialisation

    Secondary Outcome Measures

    Rate of observed and predicted death by the SCORTEN
    Duration of hospitalisation according to our historical cohort related to BSA involved
    Duration of hospitalisation according to our historical cohort related to onset of the disease
    Duration of hospitalisation according to our historical cohort related to SCORTEN
    Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes)
    Rate of sepsis
    Rate of intensive care transfer
    Rate of sequelae
    Th1/Th2 immune response in the peripheral blood of the patients
    Evaluation of expression profile of Th1/Th2 associated chemokines and anti-inflammatory chemokines in the peripheral blood
    Epidermal chimerism study on healed skin biopsy
    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.

    Full Information

    First Posted
    November 30, 2020
    Last Updated
    May 2, 2022
    Sponsor
    Assistance Publique - Hôpitaux de Paris
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04711200
    Brief Title
    LYell SYndrome MEsenchymal Stromal Cells Treatment
    Acronym
    LYSYME
    Official Title
    Mesenchymal Stromal Cells Treatment in Lyell Syndrome: A Pilot Phase 1-2 Open Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2022 (Anticipated)
    Primary Completion Date
    September 2025 (Anticipated)
    Study Completion Date
    September 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Assistance Publique - Hôpitaux de Paris

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    15 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Adipose derived stromal cells intravenously injected
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Adipose derived stromal cells intravenously injected
    Intervention Description
    2×10^6/kg of Adipose derived stromal cells A single injection at D0 (performed maximum three days post-admission).
    Primary Outcome Measure Information:
    Title
    Safety : Observation of at least one adverse effect
    Time Frame
    Day 10
    Title
    Efficacy : Rate of complete or almost complete reepithelialisation
    Time Frame
    Day 7 after infusion
    Secondary Outcome Measure Information:
    Title
    Rate of observed and predicted death by the SCORTEN
    Time Frame
    at one month
    Title
    Duration of hospitalisation according to our historical cohort related to BSA involved
    Time Frame
    Month 12
    Title
    Duration of hospitalisation according to our historical cohort related to onset of the disease
    Time Frame
    Month 12
    Title
    Duration of hospitalisation according to our historical cohort related to SCORTEN
    Time Frame
    Month 12
    Title
    Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes)
    Time Frame
    at Month 12
    Title
    Rate of sepsis
    Time Frame
    at Month 12
    Title
    Rate of intensive care transfer
    Time Frame
    at Month 12
    Title
    Rate of sequelae
    Time Frame
    at Month 12
    Title
    Th1/Th2 immune response in the peripheral blood of the patients
    Time Frame
    after injection at Day 0, Day 10, Month 1
    Title
    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.
    Title
    Epidermal chimerism study on healed skin biopsy
    Time Frame
    at 1 month
    Title
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Saskia Oro, MD
    Phone
    0149812536
    Ext
    +33
    Email
    saskia.oro@aphp.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    Myriem Carrrier, MSc
    Phone
    0144841752
    Email
    myriem.carrier@aphp.fr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Saskia Oro, MD
    Organizational Affiliation
    saskia.oro@aphp.fr
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    17805350
    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.
    Results Reference
    background
    PubMed Identifier
    27317286
    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.
    Results Reference
    background
    PubMed Identifier
    21367635
    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.
    Results Reference
    background
    PubMed Identifier
    19780713
    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.
    Results Reference
    background
    PubMed Identifier
    28476287
    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. Erratum In: Lancet. 2017 Oct 28;390(10106):1948.
    Results Reference
    result

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    LYell SYndrome MEsenchymal Stromal Cells Treatment

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