Toxic Epidermal NecrolysisPhase 1/2NET-CD38NCT07110662
New Therapeutic Target for Toxic Epidermal Necrolysis (TEN) Using Anti-CD38+ Monoclonal Antibodies.
A Phase 1/2 study testing DARATUMUMAB (DARZALEX®) in people with Toxic Epidermal Necrolysis and Immunotherapy, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Toxic Epidermal Necrolysis, Immunotherapy, Cutaneous Adverse Drug Reactions (CADR)
- What is being tested?
- DARATUMUMAB (DARZALEX®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteFrance
- Study dates
- 29 Oct 2025to 29 Apr 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
Reference Center for Toxic, Toxin and Toxidermal Bullous Dermatoses - E. Herriot Hospital
Lyon, 69437
Benoit BENSAID, Hospital practitioner, +33 4 72 11 72 11, benoit.ben-said@chu-lyon.fr
Florence HACARD, Doctor
About this study
Official title: New Therapeutic Approach to Toxic Epidermal Necrolysis (TEN) Using Anti-CD38+ Antibodies in the Active Phase of the Disease - Phase I/II Study to Assess the Tolerance and Efficacy of DARATUMUMAB.
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.
- Being tested
- DARATUMUMAB (DARZALEX®)
- Keywords
- Toxic Epidermal Necrolysis (TEN), Stevens-Johnson Syndrome (SJS), anti-CD38+, DARATUMUMAB, Simon design, Lyell syndrome
- Medical subject headings
- Stevens-Johnson Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DARATUMUMAB (DARZALEX®)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Single intravenous infusion of DARATUMUMAB 16 mg/kg body weight. Receives: Drug: DARATUMUMAB (DARZALEX®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
From baseline up to 24 hours after end of infusion: tolerance criteria defined as occurence of infusion related reactions, Cytokine release syndrome, main hemostasis parameters or variation in main biological parameters (blood ionogram).
Tolerance criteria according to NCI-CTCAE v5 criteria is defined as occurence of infusion related reactions; Cytokine release syndrome is characterized by increased levels of serum pro-inflammatory mediators; Main hemostasis parameters (prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FBG), thromobin time (TT), and D-dimer (DD); Variation in main biological parameters (blood ionogram).
Measured: At baseline and 24 hours after completion of the infusion of DARZALEX. If a clinical symptom or reaction is observed during infusion, an additional blood samples will be taken after a single intravenous infusion of DARZALEX 16 mg/kg body weight at day 1.
Efficacy defined as stop of disease progression at Day 6
The cessation of disease progression at day 6 (D6) will be assessed by evaluating the change in the percentage of body surface area with skin detachment (detached and/or bullous surfaces, and/or associated with Nikolsky's sign) between the baseline (before daratumumab administration) and day 6 (D6), according to the following rules :
- ≤ 2% for Stevens-Johnson Syndrome,
- ≤ 5% for overlap syndrome
- ≤ 10% for Lyell syndrome And without any new lesion with skin detachment. The percentage of body surface area with skin detachment will be evaluated based on the stable burn table using the E-Burn® application Day 6 after an intravenous injection of darzalex (16mg/kg) in addition to the reference symptomatic treatment (Day 1 = infusion of darzalex treatment)
Measured: Day 6 after an intravenous injection of darzalex (16mg/kg)
The occurrence of grade 3 or higher cardiovascular, renal, thyroid, or intestinal adverse events within two months of injection (seven times the nine-day half-life of daratumumab)
Occurrence of grade >=3 cardiovascular, renal, thyroid or intestinal adverse events, according to NCI-CTCAE v5 criteria.
Measured: Up to 2 months after the DARATUMUMAB infusion.
Secondary outcomes (6)
Measure time between index date (onset of first symptom) and initiation of DARATUMUMAB treatment (Day 1)
Total number of days between the unique intravenous infusion of DARATUMUMAB at day 1 and onset of first symptoms leading to the diagnosis of TEN (Toxic Epidermal Necrolysis)
Measured: From date of onset of first symptoms leading to the diagnosis of TEN (Toxic Epidermal Necrolysis) until the unique infusion of DARATUMUMAB treatment at (Day 1)]
Stop TEN progression delay: Time in days from start of DARATUMUMAB injection (Day 1) to cessation of progression
Total number of days between intravenous infusion of DARATUMUMAB (day 1) and the documented stopping progression of TEN
Measured: From the date of DARATUMUMAB infusion (Day 1) until the documented date of stopping progression of TEN, assessed up to 12 months or date of death from any cause
Complete re-epidermalization delay: Time in days from start of DARATUMUMAB infusion (Day 1) to complete re-epidermalization
The complete re-epidermalization is defined as disappearance of skin erosions AND return to normal skin. The complete re-epidermalization is the total number of days between DARATUMUMAB injection (day 1) to complete re-epidermalization.
Measured: From the date of DARATUMUMAB infusion (day 1) until the documented date of complete re-epidermization, assessed up to 12 months or date of death from any cause.
Hospital stay : measure the length of stay in one of the intensive care, burn, or internal medicine departments at Hôpital Édouard Herriot.
Length of stay in E. Herriot hospital units care: Time between admission and discharge from E Herriot hospital
Measured: From admission to end of 12-month follow-up period
Co-morbidities associated with the NET: document ophthalmological, gynecological, pulmonary, digestive, psychiatric, urological, stomatological/ORL, dermatological, hepatic, nephrological sequelae at 2, 6 and 12 months after Day1 (injection of Darzalex).
Absence or presence of any co-morbitity: ophthalmological, gynecological, pulmonary, digestive, psychiatric, urological, stomatological/ORL, dermatological, hepatic and nephrological adverse event related to the disease and grade according to NCI-CTCAE v5 criteria.
Measured: At 2 months, 6 months and 12 months after Day 1 (injection of Daratumumab)
Overall survival measure at Day 15 and 12 months after Darzalex infusion (D1)
Overall survival rate defined as percentage of deaths
Measured: At Day15 and 12 months after Darzalex infusion (Day 1).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2025
- Study start29 Oct 2025 (estimated)
- Primary completion29 Oct 2028 (estimated)
- Study completion29 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Toxic Epidermal NecrolysisStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a prospective, single-center, open-label phase I/II study using an optimal two-stage SIMON-type design for efficacy/tolerance evaluation (Simon, 1989), with an additional stage for tolerance evaluation alone... : 1. After the first three inclusions, and two months of follow-up, a safety analysis with an opinion from the Independent Study Monitoring Board (DSMB) and an efficacy analysis (Simon's plan) will be carried out. If the rules allow (at least one patient with cessationof progression and a positive opinion from the DSMB concerning safety), 3 new patients will be included. 2. After the first 6 inclusions and two months' follow-up, a safety analysis with a DSMB opinion will be carried out. If the DSMB opinion is favorable, 3 additional patients will be included. The 2-month follow-up period is sufficient for the collection of clinico-biological criteria of interest.
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen-Cilag Ltd., INSERM U1111
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07110662
- Sponsor's protocol ID
- 69HCL23_1000
- Other IDs
- 2024-512164-63-00, 2024-512164-63-00
- Acronym
- NET-CD38
- Status last verified
- Jul 2025
- First submitted
- 21 Jul 2025
- Last updated
- 7 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- New Therapeutic Approach to Toxic Epidermal Necrolysis (TEN) Using Anti-CD38+ Antibodies in the Active Phase of the Disease - Phase I/II Study to Assess the Tolerance and Efficacy of DARATUMUMAB.
- ClinicalTrials.gov ID
- NCT07110662
- Acronym / sponsor ID
- NET-CD38 / 69HCL23_1000
- Keywords
- Toxic Epidermal Necrolysis (TEN), Stevens-Johnson Syndrome (SJS), anti-CD38+, DARATUMUMAB, Simon design, Lyell syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Collaborators
- Janssen-Cilag Ltd., INSERM U1111
- Study start
- 29 Oct 2025 (estimated)
- Primary completion
- 29 Oct 2028 (estimated)
- Study completion
- 29 Apr 2029 (estimated)
- First posted
- 7 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a prospective, single-center, open-label phase I/II study using an optimal two-stage SIMON-type design for efficacy/tolerance evaluation (Simon, 1989), with an additional stage for tolerance evaluation alone... : 1. After the first three inclusions, and two months of follow-up, a safety analysis with an opinion from the Independent Study Monitoring Board (DSMB) and an efficacy analysis (Simon's plan) will be carried out. If the rules allow (at least one patient with cessationof progression and a positive opinion from the DSMB concerning safety), 3 new patients will be included. 2. After the first 6 inclusions and two months' follow-up, a safety analysis with a DSMB opinion will be carried out. If the DSMB opinion is favorable, 3 additional patients will be included. The 2-month follow-up period is sufficient for the collection of clinico-biological criteria of interest.
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: DARATUMUMAB (DARZALEX®)Single intravenous infusion of DARATUMUMAB 16 mg/kg body weight. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Experimental |
Primary outcome
From baseline up to 24 hours after end of infusion: tolerance criteria defined as occurence of infusion related reactions, Cytokine release syndrome, main hemostasis parameters or variation in main biological parameters (blood ionogram).
Time frame: At baseline and 24 hours after completion of the infusion of DARZALEX. If a clinical symptom or reaction is observed during infusion, an additional blood samples will be taken after a single intravenous infusion of DARZALEX 16 mg/kg body weight at day 1.
Tolerance criteria according to NCI-CTCAE v5 criteria is defined as occurence of infusion related reactions; Cytokine release syndrome is characterized by increased levels of serum pro-inflammatory mediators; Main hemostasis parameters (prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FBG), thromobin time (TT), and D-dimer (DD); Variation in main biological parameters (blood ionogram).
Efficacy defined as stop of disease progression at Day 6
Time frame: Day 6 after an intravenous injection of darzalex (16mg/kg)
The cessation of disease progression at day 6 (D6) will be assessed by evaluating the change in the percentage of body surface area with skin detachment (detached and/or bullous surfaces, and/or associated with Nikolsky's sign) between the baseline (before daratumumab administration) and day 6 (D6), according to the following rules : * ≤ 2% for Stevens-Johnson Syndrome, * ≤ 5% for overlap syndrome * ≤ 10% for Lyell syndrome And without any new lesion with skin detachment. The percentage of body surface area with skin detachment will be evaluated based on the stable burn table using the E-Burn® application Day 6 after an intravenous injection of darzalex (16mg/kg) in addition to the reference symptomatic treatment (Day 1 = infusion of darzalex treatment)
The occurrence of grade 3 or higher cardiovascular, renal, thyroid, or intestinal adverse events within two months of injection (seven times the nine-day half-life of daratumumab)
Time frame: Up to 2 months after the DARATUMUMAB infusion.
Occurrence of grade >=3 cardiovascular, renal, thyroid or intestinal adverse events, according to NCI-CTCAE v5 criteria.
6 secondary outcomes
Measure time between index date (onset of first symptom) and initiation of DARATUMUMAB treatment (Day 1)
Time frame: From date of onset of first symptoms leading to the diagnosis of TEN (Toxic Epidermal Necrolysis) until the unique infusion of DARATUMUMAB treatment at (Day 1)]
Stop TEN progression delay: Time in days from start of DARATUMUMAB injection (Day 1) to cessation of progression
Time frame: From the date of DARATUMUMAB infusion (Day 1) until the documented date of stopping progression of TEN, assessed up to 12 months or date of death from any cause
Complete re-epidermalization delay: Time in days from start of DARATUMUMAB infusion (Day 1) to complete re-epidermalization
Time frame: From the date of DARATUMUMAB infusion (day 1) until the documented date of complete re-epidermization, assessed up to 12 months or date of death from any cause.
Hospital stay : measure the length of stay in one of the intensive care, burn, or internal medicine departments at Hôpital Édouard Herriot.
Time frame: From admission to end of 12-month follow-up period
Co-morbidities associated with the NET: document ophthalmological, gynecological, pulmonary, digestive, psychiatric, urological, stomatological/ORL, dermatological, hepatic, nephrological sequelae at 2, 6 and 12 months after Day1 (injection of Darzalex).
Time frame: At 2 months, 6 months and 12 months after Day 1 (injection of Daratumumab)
Overall survival measure at Day 15 and 12 months after Darzalex infusion (D1)
Time frame: At Day15 and 12 months after Darzalex infusion (Day 1).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DARATUMUMAB (DARZALEX®) in people with Toxic Epidermal Necrolysis and Immunotherapy, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Benoit BENSAID, Hospital practitioner (+33 4 72 11 72 11, benoit.ben-said@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
From baseline up to 24 hours after end of infusion: tolerance criteria defined as occurence of infusion related reactions, Cytokine release syndrome, main hemostasis parameters or variation in main biological parameters (blood ionogram). (time frame: At baseline and 24 hours after completion of the infusion of DARZALEX. If a clinical symptom or reaction is observed during infusion, an additional blood samples will be taken after a single intravenous infusion of DARZALEX 16 mg/kg body weight at day 1.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.