Maintenance of Remission With Rituximab Versus Azathioprine for Newly-diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis.

NCT03164473 | Completed Phase 3 DMC

• 2 other identifiers: P1509222016-000627-53
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate, after achievement of remission, the efficacy of rituximab compared with azathioprine maintenance therapy on duration of remission, in patients with relapsing or newly-diagnosed Eosinophilic granulomatosis with polyangiitis EPGA receiving standard of care therapy including glucocorticoid therapy reduction/withdrawal.

Conditions

Eosinophilic Granulomatosis With Polyangiitis

Keywords

Eosinophilic granulomatosis with polyangiitis in remission; double-blind randomized controlled trial; maintenance therapy; rituximab versus azathioprine; vasculitis remission; asthma control; rhinosinusal manifestations control; glucocorticoid therapy reduction/withdrawal; steroid sparing effect; damage

Outcome Measures

Primary Outcomes (1)

• Duration of remission in weeks

  accrued number of weeks where a patient remains in remission with BVAS=0 and prednisone dose ≤7.5 mg/day

  28 months

Secondary Outcomes (21)

• proportion of patients remaining in remission with a BVAS=0 and prednisone dose ≤7.5 mg/day

  28 months

• Accrued number of weeks where a patient remains in remission with BVAS=0 and prednisone dose ≤4 mg/day

  28 months

• proportion of patients remaining in remission with a BVAS=0 over the 28 months study period

  28 months

• proportion of participants who achieved remission of vasculitis (BVAS = 0) while receiving prednisone at a dose of 4.0 mg or less per day at month 6

  6 months

• proportion of participants who achieved remission of vasculitis (BVAS = 0) while receiving prednisone at a dose of 4.0 mg or less per day at month 12

  12 months

Study Arms (2)

Rituximab

EXPERIMENTAL

* pre-emptive 500-mg fixed-dose of IV rituximab every 6 months (total duration of 18 months = 4 infusions) * plus orally placebo-azathioprine for 24 months

Drug: Rituximab; Drug: Placebo-azathioprine

Azathioprine

ACTIVE COMPARATOR

* standard maintenance oral azathioprine therapy (2 mg/kg/day) for 24 months * plus 4 placebo-rituximab infusions given every 6 months for 18 months

Drug: Azathioprine; Drug: Placebo-rituximab

Interventions

Rituximab DRUG

pre-emptive 500-mg fixed-dose of IV rituximab every 6 months (total duration of 18 months = 4 infusions)

Rituximab

Azathioprine DRUG

oral tablets : 2 mg/kg/day for 24 months

Azathioprine

Placebo-rituximab DRUG

4 infusions for 18 months

Azathioprine

Placebo-azathioprine DRUG

oral tablets for 24 months

Rituximab

Eligibility Criteria

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

You may qualify if:

• years of age or more
• with newly-diagnosed EGPA or after a vasculitis flare and remission achieved within the past year
• independently of ANCA status
• within 30-360 days following achievement of vasculitis remission (corresponding to a Birmingham Vasculitis Activity Score (BVAS)=0) achieved with an induction regimen including the one used in the REOVAS trial: either CS alone or in association with CYC (total dose ranging from 4.5-10 g for patients \<65 years old and from 3-10g for patients ≥65 years old) or RTX (2 x 1g (D1, D15) or 4 weekly 375 mg/m2).
• with a stable prednisone dose for 30 days or no more prednisone
• after oral immunosuppressive drug cessation if started at remission.
• Patients included in the REOVAS trial and achieving remission can be included at month 12 visit if they fulfil the other criteria
• Patients able to give written informed consent prior to participation in the study.
• Affiliation with a mode of social security (profit or being entitled).

You may not qualify if:

• patients with GPA, MPA or other vasculitides
• patients with vasculitis not in remission defined as a BVAS \>0
• acute or chronic active infections (including HIV, HBV or HCV)
• active or recent cancer ( \<5 years), except basocellular carcinoma and low activity prostatic cancer controlled by hormonal treatment
• severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
• pregnant women and lactation
• patients with childbearing potential will have reliable contraception for all the duration of the study and another 12 months after. Women are considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient
• men who refuse to use effective method of contraception (condom) from the date of consent through the end of the study
• patients who had already been treated with rituximab before the last relapse/flare
• patients who have been treated with rituximab with a different induction regimen than 2 x 1g (D1, D14) or 4 weekly 375 mg/m2 infusions
• hypersensitivity to a monoclonal antibody or biologics
• contraindication to rituximab or azathioprine
• other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation
• patients included in other investigational therapeutic study within the previous 3 months except in the REOVAS trial, after which patients achieving remission can be included if they fulfil the other criteria
• patients suspected not to be observant to the proposed treatments

Sponsors & Collaborators

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

Study Sites (1)

Hôpital Cochin

Paris, Paris, 75014, France

Location

MeSH Terms

Conditions

Churg-Strauss Syndrome

Interventions

Rituximab; 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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Benjamin Terrier

  National Referral Center for Rare Systemic Autoimmune Diseases - Hôpital Cochin

  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 22, 2017
• First Posted: May 23, 2017
• Study Start: March 7, 2018
• Primary Completion: September 23, 2024
• Study Completion: September 23, 2024
• Last Updated: November 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)