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

• Register: ClinicalTrials.gov
• Last refreshed on: 9 January 2023
• Main ID: NCT03164473
• Date of registration: 22/05/2017
• Prospective Registration: Yes
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: Maintenance of Remission With Rituximab Versus Azathioprine for Newly-diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis. MAINRITSEG
• Scientific 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
• Date of first enrolment: March 7, 2018
• Target sample size: 98
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03164473
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

France

Contacts

• Name: Benjamin Terrier
• Affiliation: National Referral Center for Rare Systemic Autoimmune Diseases - Hôpital Cochin

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- 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).

Exclusion Criteria:

- 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

- 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Eosinophilic Granulomatosis With Polyangiitis

Intervention(s)

Drug: Placebo-azathioprine

Drug: Azathioprine

Drug: Rituximab

Drug: Placebo-rituximab

Primary Outcome(s)

Duration of remission in weeks [Time Frame: 28 months]

Secondary Outcome(s)

damage assessed by the mean variation of the Vasculitis Damage Index (VDI) [Time Frame: 28 months]

prednisone dose at months 6, 12, 18, 24 and 28, and area under the curve over the 28 month study period [Time Frame: 28 months]

time to first vasculitis relapse [Time Frame: 28 months]

proportion of patients remaining in remission with a BVAS=0 [Time Frame: 28 months]

proportion of patients remaining in remission with a BVAS=0 and prednisone dose =7.5 mg/day [Time Frame: 28 months]

proportion of patients with at least one clinically significant asthma/rhino-sinusal exacerbation [Time Frame: 28 months]

proportion of patients with selected severe adverse events including grade 3 or 4 adverse effects (Common Terminology Criteria for Adverse Events) [Time Frame: 28 months]

proportion of patients with at least one vasculitis relapse (major, minor, either) [Time Frame: 28 months]

time to first clinically significant asthma/rhino-sinusal exacerbation [Time Frame: 28 months]

proportion of patients with adverse events [Time Frame: 28 months]

disability assessed by the mean variation of the Health Assessment Questionnaire (HAQ) [Time Frame: 28 months]

number of days of hospitalization [Time Frame: 28 months]

proportion of patients with serious adverse events [Time Frame: 28 months]

quality of life assessed by the mean variation of the SF-36 [Time Frame: 28 months]

number and causes of deaths over the 28 month study period [Time Frame: 28 months]

variation of the obstructive pulmonary disease [Time Frame: 28 months]

Secondary ID(s)

2016-000627-53

P150922

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

French Vasculitis Study Group