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

NCT06734884 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 2020_572022-502750-14-00
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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

Keywords

DRESS syndrome; drug hypersensitivity; Eosinophil; Benralizumab; targeted therapy

Outcome Measures

Primary Outcomes (1)

• 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)

  Number of days spent in hospital for the management of DRESS syndrome

  from inclusion to 52 weeks

Secondary Outcomes (5)

• Percentage of body surface with cutaneous lesions due to DRESS and severity grade of skin involvement observed within the 52 weeks period

  at Day4, Day 7, Week 2, Week 4, Week 12, Week 24 and Week 52

• Number and severity grade of organ lesions due to DRESS observed within the 52 weeks period

  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.

• Dosage of blood eosinophils during the 52 weeks after inclusion

  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.

• Number of flares or relapses of DRESS during a 52 week-period after inclusion

  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.

• Consumption of topical or systemic corticosteroids during a 52 week-period after inclusion

  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

Study Arms (2)

Benralizumab

EXPERIMENTAL

Drug: Benralizumab 30 MG/ML [Fasenra]

Placebo

PLACEBO COMPARATOR

Drug: Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride

Interventions

Benralizumab 30 MG/ML [Fasenra] DRUG

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

Benralizumab

Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride DRUG

Subcutaneous injection at day 2, week 4 and week 8

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (minimum 18year-old)
• 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
• 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)
• AND Fever ≥ 38°C at the time of the examination or notion of a thermal peak ≥ 38°C in the preceding 72 hours.
• 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).

You may not qualify if:

• Patients \<18 year-old
• Patients with DRESS with REGIScar score \<4
• Patients without skin eruption at baseline
• Eosinophils blood count \<500/mm3 or \< 0.5 G/L at baseline
• Patients with contra-indication to blood samples dedicated to the biocollection, according to the investigator's opinion
• Patients with contra-indication to stop the culprit drug(s) involved in DRESS
• Past history of hypersensitivity to biological drugs
• Patients with a contra-indication of topical corticosteroids (mainly a past history of contact eczema with clobetasol propionate)
• Pregnancy and lactation

Sponsors & Collaborators

• University Hospital, Lille: lead
• AstraZeneca: collaborator

Study Sites (1)

Delphine STAUMONT-SALLE

Lille, Nord, 59000, France

Location

MeSH Terms

Conditions

Drug Hypersensitivity Syndrome; Drug Hypersensitivity

Interventions

benralizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Delphine STAUMONT-SALLE, Professor, MD

CONTACT

+33320444145; DRC@chu-lille.fr

Japhete ELENGA KOANGA

CONTACT

+33320444145; japhete.elengakoanga@chu-lille.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: December 16, 2024
• Study Start: January 6, 2025
• Primary Completion (Estimated): January 5, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: January 17, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

FR (1)