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Eosinophilic Granulomatosis With PolyangiitisPhase 3MAINRITSEGNCT03164473

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

A Phase 3 study testing Rituximab and Azathioprine in people with Eosinophilic Granulomatosis With Polyangiitis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Rituximab and Azathioprine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
98 participants
Where
1 siteFrance
Study dates
7 Mar 2018to 23 Sep 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • patients with a diagnosis of EGPA according to Lanham and/or ACR 1990 criteria and/or Revised Chapel Hill Nomenclature and/or MIRRA study inclusion criteria
  • 18 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
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  • 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).

Who cannot join

  • 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
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  • 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
  • white blood cell count ≤4,000/mm3
  • platelet count ≤100,000/mm3
  • ALT or AST level >3 times the upper limit of normal
  • patients not able to stop allopurinol and febuxostat which may enhance azathioprine toxicity
  • patients unable to give written informed consent prior to participation in the study.

Trial locations and contacts

1 site in 1 country.

France1 site
  • Hôpital Cochin

    Paris, Paris, 75014

Other trials in France

About this study

Official title: MAINtenance of Remission With RITuximab Versus Azathioprine for Patients With Newly-diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis. A Prospective, Randomized, Controlled, Double-blind Study: the MAINRITSEG Trial

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.

Read the detailed description

Rituximab, an anti-CD20 monoclonal antibody, has been shown to be as effective as cyclophosphamide to induce GPA and MPA remission, with an acceptable safety profile, leading to its registration by the FDA and EMA as remission-induction therapy in these patients.

In addition, the MAINRITSAN trial has demonstrated that 500 mg rituximab given every 6 months for 18 months was significantly more effective than azathioprine standard of care to maintain remission in patients with GPA or MPA, with a similar profile of tolerance.

EGPA patients were excluded from these trials. Long-term studies have shown that only 29% of EGPA patients achieved long-term remission and that relapses occurred in more than 40% of them, leading to high cumulative morbidity and damage. Moreover, most patients cannot be weaned off corticosteroids due to asthma and rhino-sinusal manifestations, even after vasculitis remission.

However, recent retrospective series indicated that rituximab may also be an effective remission induction and maintenance agent in refractory or relapsing EGPA. REOVAS, the first randomized controlled trial with rituximab as induction therapy in EGPA, has started within the French Vasculitis Study Group network.

The MAINRITSEG trial is a phase III, comparative, multicenter, randomized, double-blind, double-dummy and superiority trial, comparing pre-emptive low-dose rituximab-based regimen with azathioprine standard therapy, for the remission maintenance in newly-diagnosed or relapsing EGPA.

Patients, with newly diagnosed or relapsing EGPA, after achievement of remission, will be randomized in a 1:1 ratio to receive:

  • Standard regimen: maintenance oral azathioprine (2 mg/kg/day) for 24 months. This control group will receive conventional therapy plus 4 infusions of placebo-rituximab (every 6 months for 18 months)
  • Experimental regimen: pre-emptive 500-mg fixed-dose of rituximab every 6 months for 18 months (4 infusions). This group will receive intravenous rituximab plus orally placebo-azathioprine for 24 months.

All patients will receive standard of care therapy including glucocorticoid therapy reduction/withdrawal.

Being tested
Rituximab, Azathioprine, Placebo-rituximab, Placebo-azathioprine
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
Medical subject headings
Churg-Strauss Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

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

  • AzathioprineDrug

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

  • Placebo-rituximabDrug

    4 infusions for 18 months

  • Placebo-azathioprineDrug

    oral tablets for 24 months

Study groups in NCT03164473
Study groupRoleWhat they receive
RituximabExperimental* 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
Receives: Drug: Rituximab; Drug: Placebo-azathioprine
AzathioprineActive 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
Receives: Drug: Azathioprine; Drug: Placebo-rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 28 months

Secondary outcomes (21)
  1. proportion of patients remaining in remission with a BVAS=0 and prednisone dose ≤7.5 mg/day

    Measured: 28 months

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

    Measured: 28 months

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

    Measured: 28 months

  4. 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

    Measured: 6 months

  5. 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

    Measured: 12 months

  6. 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 18

    Measured: 18 months

  7. 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 28

    Measured: 28 months

  8. proportion of patients with at least one vasculitis relapse (major, minor, either)

    Measured: 28 months

  9. proportion of patients with at least one clinically significant asthma/rhino-sinusal exacerbation

    defined as a worsening of asthma/rhino-sinusal disease leading to the doubling (or more) of the existing maintenance dose of corticosteroids for 3 or more days or hospital admission or an emergency department visit.

    Measured: 28 months

  10. time to first vasculitis relapse

    Measured: 28 months

  11. time to first clinically significant asthma/rhino-sinusal exacerbation

    defined as a worsening of asthma/rhino-sinusal disease leading to the doubling (or more) of the existing maintenance dose of corticosteroids for 3 or more days or hospital admission or an emergency department visit.

    Measured: 28 months

  12. variation of the obstructive pulmonary disease

    assessed by change of FEV1 at pulmonary function tests after use of a bronchodilator

    Measured: 28 months

  13. prednisone dose at months 6, 12, 18, 24 and 28, and area under the curve over the 28 month study period

    Measured: 28 months

  14. proportion of patients with adverse events

    Measured: 28 months

  15. proportion of patients with serious adverse events

    Measured: 28 months

  16. proportion of patients with selected severe adverse events including grade 3 or 4 adverse effects (Common Terminology Criteria for Adverse Events)

    necessitating hospitalization, all cause deaths, cancers or infusion reactions (within 24 hours of infusion) that contraindicated further infusions

    Measured: 28 months

  17. number and causes of deaths over the 28 month study period

    Measured: 28 months

  18. damage assessed by the mean variation of the Vasculitis Damage Index (VDI)

    Measured: 28 months

  19. quality of life assessed by the mean variation of the SF-36

    Measured: 28 months

  20. disability assessed by the mean variation of the Health Assessment Questionnaire (HAQ)

    Measured: 28 months

  21. number of days of hospitalization

    Measured: 28 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2017
  2. Study start7 Mar 2018
  3. Primary completion23 Sep 2024
  4. Study completion23 Sep 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03164473
Sponsor's protocol ID
P150922
Other IDs
2016-000627-53, 2016
Acronym
MAINRITSEG
Status last verified
Oct 2025
First submitted
22 May 2017
Last updated
20 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Puechal X, Pugnet G, Thoreau B, de Moreuil C, Jouneau S, Quemeneur T, Baron G, Smets P, Neel A, Le Gallou T, Noel N, Uzunhan Y, Comarmond-Ortoli C, Urbanski G, Benhamou Y, Berezne A, Mekinian A, Hamidou M, Campagne J, Abisror N, Cohen P, Guillevin L, Ravaud P, Terrier B; French Vasculitis Study Group. Rituximab vs Azathioprine for Eosinophilic Granulomatosis With Polyangiitis Maintenance Therapy: A Randomized Clinical Trial. JAMA. 2026 Oct 22:e2615278. doi: 10.1001/jama.2026.15278. Online ahead of print.

    PubMed 42911562

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rituximab and Azathioprine in people with Eosinophilic Granulomatosis With Polyangiitis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Duration of remission in weeks (time frame: 28 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03164473, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.

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