Mesenchymal stromal cells treatment in Lyell syndrome: A pilot phase 1-2 open trial (LYSYME)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

15 Apr 2024 → ongoing

Decision date (initial)

2024-11-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

DGOS - French Ministry of Health

External identifiers

EU CT number

2024-516404-42-00

EudraCT number

2020-000308-12

ClinicalTrials.gov

NCT04711200

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the safety and the efficacy i.e., complete almost complete cutaneous re-epithelialization at D7 after infusion of 2×106/kg ASCs in SJS-TEN patients.

Secondary objectives 1

1. To evaluate the impact of ASCs treatment on SJS-TEN clinical course and immunological markers.

Conditions and MedDRA coding

Adults diagnosed with SJS-TEN with at least 10% of body surface area involved

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. For patients : Patient ≥18 and ≤ 75 years-old
2. For patients : Admission ≤ 10 days after the index date (date of the first symptoms of the disease)
3. For patients : Patient with confirmed SJS-TEN diagnosis hospitalized in the department of Dermatology or intensive care medicine
4. For patients : 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)
5. For patients : 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
6. For patients : Affiliated to a social security scheme
7. For donors : Donor ≥ 18 and ≤ 55 years old
8. For donors : Admission for a programmed plastic surgery of liposuction or aspiration in the abdominal wall under general anesthesia
9. For donors : Health history questionnaire in appendix completed
10. For donors : Written consent
11. For donors : Affiliated to a social security scheme

Exclusion criteria 38

1. For patients : Pregnant or breastfeeding woman
2. For patients : Patient deprived of liberty by a judicial or administrative decision or under the protection of justice
3. For patients : Any psychological, familial, sociological or geographical condition potentially hampering compliance with the research protocol and followup schedule
4. For patients : Patient under tutorship or curatorship
5. For patients : Patient under psychiatric care according to art. L1121-6 CSP
6. For donors : Positive viral serology: HIV, HBV (An anti HBc antibody isolated without detection of viral genome (HBV NAT) and HBsAg can be considered as acceptable), HCV, HEV, syphilis, HTLV, active infection with IgM+ for toxoplasmosis, EBV, CMV
7. For donors : Detection of Coronavirus SARS CoV-2 RNA on screening (positive RTPCR), if performed in the usual care
8. For donors : Deprived of freedom
9. For donors : Significant comorbidities according to donor health history, if considered to be clinically significant by the investigator
10. For donors : Treatment with extractive pituitary hormones (including growth hormones)
11. For donors : Human dura mater transplant
12. For patients : History of malignant disease within the past ten years and or presence of metastasis
13. For donors : Surgical history of the central nervous system
14. For donors : Dementia or neurological disease that may evoke subacute spongiform encephalopathy
15. For donors : Family history as part of subacute spongiform encephalopathy
16. For donors : Hematological malignancies
17. For donors : Active or cured cancer
18. For donors : System or connective tissue disease
19. For donors : Active generalized infection (bacterial, viral, parasitic, tuberculosis, leprosy...)
20. For donors : Multiple adenopathy, splenomegaly, hepatomegaly at clinical examination
21. For donors : Icterus
22. For donors : Chemotherapy history, irradiation
23. For patients : Positive serology for HIV
24. For donors : Long-term systemic steroids (duration > 30 days within the 5 past years or within 1 month before inclusion, at any dose)
25. For patients : Active infection for hepatitis B or C
26. For patients : Detection of Coronavirus SARS CoV-2 RNA on admission (positive RTPCR), if performed in the usual care
27. For patients : Decompensated cardiac failure
28. For patients : Uncontrolled epilepsia
29. For patients : Previous history or allogenic bone marrow transplantation
30. For patients : Participation in other interventional drug research
31. For donors : Authenticated risk factors for viral infections in the past 12 months : o Multiple sexual partners (donor or regular partner) o Intravenous addiction (donor or regular partner) o Accident of exposure to blood or derivatives suspected of being contaminated
32. For donors : Topical steroids on abdominal wall within 1 month before inclusion
33. For donors : Contraindication to general anesthesia
34. For donors : Body mass index <18.5 or >30 kg/m2
35. For donors : Active smoking
36. For donors : Unbalanced diabetes or treated by insuline
37. For donors : Donors who present a risk according to current health alerts and recommendations from ANSM, ABM and SECPROCH at the time of inclusion
38. For donors : In addition, any donor patient presenting an exclusion criterion or any element considered to be clinically significant in appendix will not be included

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety: The toxicity is defined as the observation of at least one adverse effect
2. Efficacy: Rate of complete almost complete reepithelialisation at D7 after infusion. This criterion is defined as at least 90% of cutaneous body surface area (BSA) healed at D7 in comparison to maximal cutaneous detachable-detached BSA observed.

Secondary endpoints 10

1. Rate of observed and predicted death at one month by the SCORTEN scale
2. Duration of hospitalisation according to our historical cohort
3. Duration of each mucous membrane healing i.e. (buccal, nasal, genital, eyes).
4. Rate of sepsis
5. Rate of intensive care transfer
6. Rate of sequelae at M12
7. Th1/Th2 immune response in the peripheral blood of the patients after injection at D0, D10, M1
8. Evaluation of expression profile of Th1/Th2 associated chemokines and anti-inflammatory chemokines in the peripheral blood after injection at D0, D10, M1.
9. Epidermal chimerism research on healed skin biopsy and peripheral blood at 1 month.
10. Rate of complete or almost complete reepithelialisation at D5, D10 and D15 after infusion.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Saskia ORO

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Saskia ORO

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications