Clinical trial NCT06734884: Interest of a Targeted Therapy for the Treatment of a Severe Form of Hypersensitivity to Drug (DRESS Syndrome)
Official title: Efficacy and Safety of Anti-interleukin 5 Receptor Therapy (Benralizumab) in Patients With Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: DRESS Syndrome
Keywords: DRESS syndrome
drug hypersensitivity
Eosinophil
Benralizumab
targeted therapy
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2024-12-16
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Drug Reaction with eosinophilia and Systemic Symptoms (DRESS) is a rare and severe multiorgan drug reaction whose pathophysiological mechanisms underlying remain unclear, but may involve the role of several immune cells like eosinophils. iIndeed,the number of eosinophils is increased in blood and/or in organs tiisues in at least 50% of patients with DRESS. There is no specific treatment available. The standard of care is corticosteroids, but they may be inefficient or poorly tolerated. The aim of this research is to find out whether a specific treatment of the immunological response in DRESS syndrome would be useful in combination with corticosteroids to speed up the recovery from DRESS syndrome and therefore reduce the total length of your hospital stay when your illness is being managed. This a multicenter, international, prospective, interventional study, double-blinded, placebo-controlled, randomized, in two balanced parallel groups, one receiving the standard of care (topical or systemic corticosteroids, according to the severity of DRESS syndrome) and the other one corticsoteroids and a targeted therapy against eosinophils (benralizumab, already available in other eosinophilic diseases like asthma).


Eligibility criteria: Inclusion Criteria:

1. Adult patients (minimum 18year-old)
2. diagnosed at D0 (= baseline and inclusion) with DRESS defined by:

   1. with a REGIScar score at D0 calculated at at least 4 (4 or 5: probable DRESS; \&gt;5: definite case of DRESS), see Annex: REGIScar criteria
   2. Skin eruption with an onset considered as compatible with a DRESS syndrome according to the investigator's opinion after the uptake of one or several drug(s)
   3. AND Fever ≥ 38°C at the time of the examination or notion of a thermal peak ≥ 38°C in the preceding 72 hours.
   4. At least 1 organ disorder compatible with the diagnosis of DRESS syndrome among the following disorders:

      * Adenopathies present in at least 2 different sites and ≥ 1 cm in size
      * Acute hepatitis defined by :

        * Elevation of liver enzymes in serum: ALAT (Alanine Aminotransferase) and/or ASAT (Aspartate Aminotransferase)
        * AND/OR an increase in serum total bilirubin, according to the standards of the local analysis laboratory (in the absence of a history of liver disease: ASAT and/or ALAT ≥ 3N (=3 times normal)
        * AND/OR total bilirubin ≥ 2N
      * Acute renal failure defined by :

        * An increase in creatinine according to local laboratory standards
        * AND a sterile cytobacteriological examination (in the absence of a history of renal disease: creatininaemia ≥ 1.5N
        * AND/OR increase in creatinine ≥ 0.3 mg/dl (or ≥ 26.5 mol/L)
        * AND/OR urine output \&lt; 0.3 ml/kg/h (over ≥ 24h).
      * Pulmonary impairment defined by:

        * Oxygen saturation (SpO2) measured by pulse oximetry ≤ 95% in room air
        * And/or the presence of an interstitial syndrome on a standard chest X-ray or a CT scan of the chest (in the absence of any other cause of lung damage).
3. With eosinophilia (blood eosinophil count ≥ 500/mm3 or ≥0.5 G/L).
4. Patient having given written informed consent
5. patient with social insurance

Exclusion Criteria:

1. Patients \&lt;18 year-old
2. Patients with DRESS with REGIScar score \&lt;4
3. Patients without skin eruption at baseline
4. Eosinophils blood count \&lt;500/mm3 or \&lt; 0.5 G/L at baseline
5. Patients with contra-indication to blood samples dedicated to the biocollection, according to the investigator's opinion
6. Patients with contra-indication to stop the culprit drug(s) involved in DRESS
7. Past history of hypersensitivity to biological drugs
8. Patients who received a previous anti-IL5 or anti-IL5 receptor therapy within 5 half lives (= 4 months) before inclusion
9. Patients with a contra-indication of topical corticosteroids (mainly a past history of contact eczema with clobetasol propionate)
10. Pregnancy and lactation

Primary outcomes:
measure: Efficacity of an add-on treatment with benralizumab to decrease the total hospitalization for DRESS duration within a 52 weeks (W52) period in patients diagnosed with DRESS syndrome and treated with corticosteroids (CS)
timeFrame: from inclusion to 52 weeks
Secondary outcomes:
measure: Percentage of body surface with cutaneous lesions due to DRESS and severity grade of skin involvement observed within the 52 weeks period
timeFrame: at Day4, Day 7, Week 2, Week 4, Week 12, Week 24 and Week 52
measure: Number and severity grade of organ lesions due to DRESS observed within the 52 weeks period
timeFrame: Total number of organ lesions within 52 weeks. These organ lesions will be recorded at Day 4, Day7, Week 2, Week 4, Week 12, Week 24 and Week 52.
measure: Dosage of blood eosinophils during the 52 weeks after inclusion
timeFrame: number of cells per mm3 or per liter) performed at baseline (D0 = prior treatment), and at Day 2, Day 4, Day 7, Week 2, Week 4, Week 8, Week 12, Week 24, Week 52.
measure: Number of flares or relapses of DRESS during a 52 week-period after inclusion
timeFrame: Total number of exacerbation/worsening or occurrence/reappearance of DRESS signs identified within the Week 52 period and recorded at Day 2, Day 4, Day 7, Week 2, Week 4, Week 8, Week 12, Week 24, Week 52.
measure: Consumption of topical or systemic corticosteroids during a 52 week-period after inclusion
timeFrame: Total quantity of superpotent topical or systemic corticosteroids (CS) used at Day 7, Week 2, Week 4, Week 8, Week 12, Week 24, Week 52
Other outcomes:
Locations:
city: Lille
country: France
facility: Delphine STAUMONT-SALLE
state: Nord
Study officials:
References: