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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT07110662
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Hospices Civils de Lyon
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Not yet recruiting
Countries	France
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Toxic Epidermal Necrolysis, Immunotherapy, Cutaneous Adverse Drug Reactions (CADR)

Arms & Interventions

Arms

Experimental: Experimental

Single intravenous infusion of DARATUMUMAB 16 mg/kg body weight.

Interventions

Drug: - DARATUMUMAB (DARZALEX®)

A single injection of DARZALEX 16 mg/kg body weight administered by intravenous infusion (day 1) in addition to standard symptomatic treatment of NET until re-epidermalization.

Contact a Trial Team

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International Sites

Lyon, France

Status

Address

Reference Center for Toxic, Toxin and Toxidermal Bullous Dermatoses - E. Herriot Hospital

Lyon, , 69437

Site Contact

Benoit BENSAID, Hospital practitioner

[email protected]

+33 4 72 11 72 11

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