Interest of a Targeted Therapy for the Treatment of a Severe Form of Hypersensitivity to Drug (DRESS Syndrome)

NCT ID: NCT06734884

Last Updated: 2025-01-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-06
• Study Completion Date: 2029-09-01

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).

Conditions

DRESS Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Benralizumab

Group Type: EXPERIMENTAL

Benralizumab 30 MG/ML [Fasenra]

Intervention Type: DRUG

Subcutaneous injection 30 mg at day 2, week 4 and week 8.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride

Intervention Type: DRUG

Subcutaneous injection at day 2, week 4 and week 8

Interventions

Benralizumab 30 MG/ML [Fasenra]

Subcutaneous injection 30 mg at day 2, week 4 and week 8.

Intervention Type: DRUG

Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride

Subcutaneous injection at day 2, week 4 and week 8

Intervention Type: DRUG

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; >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 < 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 <18 year-old

2. Patients with DRESS with REGIScar score <4

3. Patients without skin eruption at baseline

4. Eosinophils blood count <500/mm3 or < 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Delphine STAUMONT-SALLE

Lille, Nord, France

Countries

France

Central Contacts

Delphine STAUMONT-SALLE, Professor, MD

Role: CONTACT

DRC@chu-lille.fr

+33320444145

Japhete ELENGA KOANGA

Role: CONTACT

japhete.elengakoanga@chu-lille.fr

+33320444145 ext. 30939

Facility Contacts

Delphine STAUMONT-SALLE, MD, Professor

Role: primary

DRC@chu-lille.fr

+33320444145

Other Identifiers

2022-502750-14-00

Identifier Type: CTIS

Identifier Source: secondary_id

2020_57

Identifier Type: -

Identifier Source: org_study_id