New Therapeutic Target for Toxic Epidermal Necrolysis (TEN) Using Anti-CD38+ Monoclonal Antibodies. (NET-CD38)

Civil Hospices of Lyon

Status and phase

Not yet enrolling

Phase 2

Phase 1

Conditions

Cutaneous Adverse Drug Reactions (CADR)

Toxic Epidermal Necrolysis

Immunotherapy

Treatments

Drug: DARATUMUMAB (DARZALEX®)

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT07110662

2024-512164-63-00 (EU Trial (CTIS) Number)

69HCL23_1000

Details and patient eligibility

About

Toxic Epidermal Necrolysis (TEN) are rare diseases that are dermatologic emergencies characterized by widespread epidermal necrosis and sloughing of skin. A hundred patients are affected each year in France. The main symptom is bullous and skin detachment > 10% which gradually progresses to extensive necrosis of the 100% BSA epidermis. The mortality rate is around 15-20% due to visceral inflammatory injuries and serious bacterial infections. The morbidity is also very important (92% at 1 year), especially ophthalmologic with high risk of blindness. There is currently no effective treatment.

Our team recently demonstrated that the severity of the disease correlates with the quantity and quality of CD8+ T lymphocytes which are activated in the active phase of disease. An activation marker has been identified, the CD38 receptor, which is very strongly expressed on the T clones responsible for the disease in the skin or blood of patients The CD38 receptor is the target of several commercial therapeutic antibodies, including DARATUMUMAB, which is currently used for the treatment of myeloma. DARATUMUMAB is a depleting antibody that eliminates cells strongly expressing this receptor.

The hypothesis is that a single intravenous infusion of DARATUMUMAB upon hospital admission of a patient with drug-induced NET would eliminate pathogenic T cells, thereby slowing disease progression, severity (% BSA with skin detachment, mortality rate) and sequelae.

Enrollment

9 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adult, over 18 years old, with drug-induced SJS/NET, proven or very strongly suspected (indirect argument of certainty) and confirmed by the evaluator.
SJS or NET or overlap syndrome evolving for less than 7 days prior to inclusion and with a progression of the detachment or rash observed within 48 hours prior to DARATUMUMAB treatment.
Negative hepatitis B screening (HBs, anti HBs and HBc).
The patient (or a trusted support person, family member, or close relative in case of emergency) must be capable of understanding the objectives of the trial and must have given free, informed, and express consent.
Patient affiliated to the Social Security system or benefiting from a similar system.
Negative beta HCG pregnancy test for women of childbearing potential and agreement to use effective contraception during the study and up to 3 months after stopping DARATUMUMAB treatment.

Exclusion criteria

Patient with Lyell syndrome induced by immunotherapy.
Known hypersensitivity to the active substance (DARZALEX) or to one of the excipients (L-histidine, L-histidine hydrochloride monohydrate, L-methionine, Polysorbate 20 Sorbitol -E420).
Patient with known hereditary fructose intolerance (HFI).
Patient with known history of chronic obstructive pulmonary disease (COPD).
Patient admitted with septic shock.
PMNs < 1,500 /mm3 on CBC at inclusion visit.
Pregnant or breast-feeding women.
Patient under protective measures (safeguard, curatorship, guardianship) or deprived of liberty.