Rituximab in Eosinophilic Granulomatosis With Polyangiitis

NCT02807103 | Completed Phase 3

• 2 other identifiers: P1409152016-000275-25
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

Brief Summary

Phase III, comparative, multicenter, randomized, controlled, double-blind and superiority research, comparing rituximab-based regimen with conventional therapeutic strategy for the induction of remission in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Patients with newly diagnosed or relapsing EGPA will be randomized in a 1:1 ratio to receive:

• Experimental therapeutic strategy based on the use of rituximab (experimental group)
• Conventional therapeutic strategy based on Five-Factor Score (FFS)-assessed disease severity (comparative group)

Conditions

Eosinophilic Granulomatosis With Polyangiitis (EGPA)

Keywords

Rituximab; remission induction; eosinophilic granulomatosis with polyangiitis

Outcome Measures

Primary Outcomes (1)

• The percentage of patients who obtained a BVAS=0 and prednisone dose ≤7.5 mg/day at day 180.

  180 days

Secondary Outcomes (11)

• Number of adverse events

  180 days

• Number of adverse events

  360 days

• Area under the curve for corticosteroids

  180 days

• Area under the curve for corticosteroids

  360 days

• Number of sequelae assessed by the Vasculitis Damage Index

  180 days

Study Arms (4)

Rituximab with FFS=0

EXPERIMENTAL

All patients in the rituximab group will receive corticosteroids with a predefined tapering schedule similar to the conventional therapy group. Patients with FFS=0 will receive 1 gram of rituximab at day 1 and day 15 as induction treatment

Drug: Rituximab

Conventional therapy with FFS=0

PLACEBO COMPARATOR

All patients will receive corticosteroids with a predefined tapering schedule similar to the experimental group. Patients with FFS=0 will receive placebo-rituximab at day 1 and day 15.

Drug: Placebo-rituximab

Rituximab with FFS≥1

EXPERIMENTAL

All patients in the rituximab group will receive corticosteroids with a predefined tapering schedule similar to the conventional therapy group. Patients with FFS≥1 will receive a total of 9 pulses : * 1 gram of rituximab at day 1 and day 15 as induction treatment * placebo-cyclophosphamide at days 1, 15, 29, 50, 71, 92, 113, 134 and 155. Maintenance therapy by azathioprine will be started at day 180 according to the standard of care of these patients, as recommended by the French Vasculitis Study Group.

Drug: Rituximab; Drug: Placebo-cyclophosphamide

Conventional therapy with FFS≥1

ACTIVE COMPARATOR

All patients will receive corticosteroids with a predefined tapering schedule similar to the experimental group. Patients with FFS≥1 will receive intravenous pulses of cyclophosphamide for a total of 9 pulses: 600 mg/m2 at days 1, 15 and 29, and then 500 mg-fixed dose at days 50, 71, 92, 113, 134 and 155. Maintenance therapy by azathioprine will be started at day 180 according to the standard of care of these patients, as recommended by the French Vasculitis Study Group.

Drug: Cyclophosphamide

Interventions

Rituximab DRUG

1 g intravenous pulse at day1 and day15

Also known as: Mabthera

Rituximab with FFS=0; Rituximab with FFS≥1

Cyclophosphamide DRUG

intravenous 9 pulses : 600 mg/m2 at days 1, 15 and 29, and then 500 mg-fixed dose at days 50, 71, 92, 113, 134 and 155.

Also known as: endoxan

Conventional therapy with FFS≥1

Placebo-cyclophosphamide DRUG

intravenous 7 pulses : at days 29, 50, 71, 92, 113, 134 and 155.

Also known as: Nacl

Rituximab with FFS≥1

Placebo-rituximab DRUG

intravenous pulses at day1 and day15

Also known as: nacl

Conventional therapy with FFS=0

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,
• Patient 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) ,
• Patient able to give written informed consent prior to participation in the study.

You may not qualify if:

• Patients with GPA, MPA, or other vasculitides, 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 Assocation
• Patients with acute infections or chronic active infections (including HIV, HBV or HCV),
• 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 rituximab within the previous 12 months,
• Patients with hypersensitivity to a monoclonal antibody or biologic agent,
• Patients with contraindication to use rituximab, cyclophosphamide, mesna or azathioprine,
• 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

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

Study Sites (1)

Hôpital Cochin

Paris, Paris, 75014, France

Location

Related Publications (1)

• Terrier B, Pugnet G, de Moreuil C, Bonnotte B, Benhamou Y, Chauveau D, Besse MC, Duffau P, Limal N, Neel A, Urbanski G, Jourde-Chiche N, Martin-Silva N, Campagne J, Mekinian A, Schleinitz N, Ackermann F, Fauchais AL, Froissart A, Le Gallou T, Uzunhan Y, Viallard JF, Berezne A, Chiche L, Taille C, Direz G, Durel CA, Godmer P, Trad S, Lambert M, de Menthon M, Quemeneur T, Cadranel J, Charles P, Dossier A, Jilet L, Guillevin L, Abdoul H, Puechal X; French Vasculitis Study Group. Rituximab Versus Conventional Therapy for Remission Induction in Eosinophilic Granulomatosis With Polyangiitis : A Randomized Controlled Trial. Ann Intern Med. 2025 Sep;178(9):1249-1257. doi: 10.7326/ANNALS-24-03947. Epub 2025 Jul 29.

  PMID: 40720835 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Churg-Strauss Syndrome

Interventions

Rituximab; Sodium Chloride; Cyclophosphamide

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Xavier PUECHAL, MD, PhD

  Centre de référence " Maladies systémiques et autoimmunes rares, en particulier Vascularites nécrosantes et Sclérodermies systémiques "

  STUDY CHAIR

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: May 20, 2016
• First Posted: June 21, 2016
• Study Start: December 5, 2016
• Primary Completion: October 21, 2020
• Study Completion: October 21, 2020
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)