Maintenance of Remission With Rituximab Versus Azathioprine for Newly-diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis. (MAINRITSEG)
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|ClinicalTrials.gov Identifier: NCT03164473|
Recruitment Status : Recruiting
First Posted : May 23, 2017
Last Update Posted : March 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|Eosinophilic Granulomatosis With Polyangiitis||Drug: Rituximab Drug: Azathioprine Drug: Placebo-rituximab Drug: Placebo-azathioprine||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||98 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||March 7, 2018|
|Estimated Primary Completion Date :||July 2022|
|Estimated Study Completion Date :||July 2022|
pre-emptive 500-mg fixed-dose of IV rituximab every 6 months (total duration of 18 months = 4 infusions)
oral tablets for 24 months
Active Comparator: Azathioprine
oral tablets : 2 mg/kg/day for 24 months
4 infusions for 18 months
- Duration of remission in weeks [ Time Frame: 28 months ]accrued number of weeks where a patient remains in remission with BVAS=0 and prednisone dose ≤7.5 mg/day
- proportion of patients remaining in remission with a BVAS=0 and prednisone dose ≤7.5 mg/day [ Time Frame: 28 months ]
- proportion of patients remaining in remission with a BVAS=0 [ Time Frame: 28 months ]
- proportion of patients with at least one vasculitis relapse (major, minor, either) [ Time Frame: 28 months ]
- proportion of patients with at least one clinically significant asthma/rhino-sinusal exacerbation [ Time Frame: 28 months ]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.
- time to first vasculitis relapse [ Time Frame: 28 months ]
- time to first clinically significant asthma/rhino-sinusal exacerbation [ Time Frame: 28 months ]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.
- variation of the obstructive pulmonary disease [ Time Frame: 28 months ]assessed by change of FEV1 at pulmonary function tests after use of a bronchodilator
- 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 ]
- proportion of patients with adverse events [ Time Frame: 28 months ]
- proportion of patients with serious adverse events [ 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 ]necessitating hospitalization, all cause deaths, cancers or infusion reactions (within 24 hours of infusion) that contraindicated further infusions
- number and causes of deaths over the 28 month study period [ Time Frame: 28 months ]
- damage assessed by the mean variation of the Vasculitis Damage Index (VDI) [ Time Frame: 28 months ]
- quality of life assessed by the mean variation of the SF-36 [ 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03164473
|Contact: Xavier Puechal, MD, PhD||+ 33 1 58 41 32 firstname.lastname@example.org|
|Contact: Severine Ait el Gaz-Poignant||+33 1 58 41 12 email@example.com|
|Paris, France, 75014|
|Contact: Xavier Puechal, MD, PhD + 33 1 58 41 32 41 firstname.lastname@example.org|
|Study Chair:||Benjamin Terrier||National Referral Center for Rare Systemic Autoimmune Diseases - Hôpital Cochin|