Study of Mepolizumab-based Regimen Compared to Conventional Therapeutic Strategy in Patients With Eosinophilic Granulomatosis With Polyangiitis (E-merge)

NCT05030155 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: D201801352020-003318-10
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare mepolizumab-based regimen to conventional therapeutic strategy for remission induction in patients with Eosinophilic Granulomatosis with Polyangiitis.

Conditions

Eosinophilic Granulomatosis With Polyangiitis

Keywords

Eosinophilic Granulomatosis with Polyangiitis; Mepolizumab; Remission induction; Conventional therapeutic

Outcome Measures

Primary Outcomes (1)

• Percentage of patients who achieved a prednisone dose of 4.0 mg or less per day at day 168, without experiencing a relapse

  EGPA relapse will be defined as worsening or persistence of active disease since the last visit characterized by: a) active vasculitis (BVAS \>0); OR b) active asthma symptoms; OR c) active nasal and/or sinus disease, warranting: i) an increased dose of prednisone compared to previous dosage and at least \>4 mg/day prednisone total daily dose or equivalent; OR ii) an increased dose or addition of immunosuppressive therapy; OR iii) hospitalisation related to EGPA worsening. A BVAS evaluation will be conducted at the time of a relapse, or as soon as possible afterwards

  Day 168

Secondary Outcomes (16)

• Prednisone dosage at days 168 and 364

  Days 168 and 364

• Area under the curve for corticosteroids at days 168 and 364

  Days 168 and 364

• Proportion of participants with a prednisone dose of 4.0 mg or less per day for 0 weeks

  Days 168 and 364

• Proportion of participants with a prednisone dose of 4.0 mg or less per day for more than 0 weeks but less than 4 weeks

  Days 168 and 364

• Proportion of participants with a prednisone dose of 4.0 mg or less per day for more than 4 weeks but less than 12 weeks

  Days 168 and 364

Study Arms (4)

Patients with FFS=0 - Mepolizumab

EXPERIMENTAL

Mepolizumab 300mg every 4 weeks until D336

Drug: Mepolizumab

Patients with FFS=0 - Placebo

PLACEBO COMPARATOR

Placebo of Mepolizumab every 4 weeks until D336

Drug: Placebo

Patients with FFS≥1 - Mepolizumab

EXPERIMENTAL

Mepolizumab 300mg every 4 weeks until D336 and placebo of Azathioprine 1mg/kg/day from D126 until D360 and placebo of cyclophosphamide/mesna at D1, D15, D28, D56, D84 and D112

Drug: Mepolizumab; Drug: Placebo

Patients with FFS≥1 - Placebo

PLACEBO COMPARATOR

Placebo of Mepolizumab every 4 weeks until D336, cyclophosphamide and mesna at D1, D15, D28, D56, D84 and D112 and Azathioprine 1mg/kg/day from D126 until D360

Drug: cyclophosphamide/azathioprine; Drug: Placebo

Interventions

Mepolizumab DRUG

300 mg/month subcutaneous

Patients with FFS=0 - Mepolizumab; Patients with FFS≥1 - Mepolizumab

cyclophosphamide/azathioprine DRUG

Patients with FFS≥1 will receive cyclophosphamide then azathioprine

Patients with FFS≥1 - Placebo

Placebo DRUG

Patients with FFS=0 will receive placebo

Patients with FFS=0 - Placebo; Patients with FFS≥1 - Mepolizumab; Patients with FFS≥1 - Placebo

Eligibility Criteria

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

You may qualify if:

• Patients with a diagnosis of EGPA independently of ANCA status,
• Patients aged of 18 years or older,
• Patients with newly-diagnosed disease or relapsing disease at the time of screening, with an active disease defined as a Birmingham Vasculitis Activity Score (BVAS) ≥3,
• Patients within the first 21 days following initiation/increase of corticosteroids at a dose ≤ 1 mg/kg/day (pulses of methylprednisolone before oral corticosteroid therapy are authorized)
• Patients having given their written informed consent prior to participation in the study.
• Patients affiliated with social security or CMU (profit or being entitled)

You may not qualify if:

• Patients with GPA, MPA, or other vasculitis, defined by the ACR criteria and/or the Chapel Hill Consensus Conference,
• Patients with vasculitis in remission of the disease defined as a BVAS \<3
• Patients with severe cardiac failure defined as class IV in New York Heart Association
• Patients with acute infections or chronic active infections (including HIV, HBV or HCV and checked in the last 12 months),
• Patients with active cancer or recent cancer (\<5 years), except basocellular carcinoma and prostatic cancer of low activity controlled by hormonal treatment,
• Pregnant women and lactation. Patients with childbearing potential should have reliable contraception for the 12 months duration of the study,
• Patients with EGPA who have already been treated with mepolizumab within the previous 12 months,
• Patients with hypersensitivity to a monoclonal antibody or biologic agent,
• Patients with contraindication to use mepolizumab, cyclophosphamide, mesna, azathioprine or maintenance therapy used for vasculitis,
• Patients with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol,
• Patients included in other investigational therapeutic study within the previous 3 months,
• Patients suspected not to be observant to the proposed treatments,
• Patients who have white blood cell count ≤4,000/mm3,
• Patients who have platelet count ≤100,000/mm3,
• Patients who have ALT or AST level greater that 3 times the upper limit of normal that cannot be attributed to underlying EGPA disease,

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• French Vasculitis Study Group: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Service de Médecine Interne, Centre de référence " Maladies systémiques et autoimmunes rares, en particulier Vascularites nécrosantes et Sclérodermies systémiques "Hôpital Cochin

Paris, 75014, France

Location

MeSH Terms

Conditions

Churg-Strauss Syndrome

Interventions

mepolizumab; Cyclophosphamide; Azathioprine

Condition Hierarchy (Ancestors)

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Loic GUILLEVIN, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: July 31, 2021
• First Posted: September 1, 2021
• Study Start: May 30, 2022
• Primary Completion: November 1, 2025
• Study Completion: November 1, 2025
• Last Updated: November 20, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)