This trial is active, not recruiting.

Condition anca-associated vasculitides
Treatments rituximab, placebo
Phase phase 3
Target CD20
Sponsor Assistance Publique - Hôpitaux de Paris
Collaborator Roche Pharma AG
Start date March 2015
End date July 2018
Trial size 97 participants
Trial identifier NCT02433522, 2012-001963-66, P110146 extended


MAINRITSAN study compared Rituximab and azathioprine as maintenance therapy for ANCA-associated vasculitides. In this study, Rituximab (5 infusions at D1, D15, M6, M12, M18) was superior to azathioprine (2 mg/kg/day) to prevent relapses of AAV 28 months after the inclusion (Guillevin et al. NEJM 2014). Nevertheless, in the follow-up study of MAINRITSAN, up to 30% of patients experienced a relapse 38 months after the last rituximab infusion (unpublished data). Right now, no randomized controlled study has been carried in order to evaluate the best duration of the maintenance treatment with rituximab.

The investigators objective is to evaluate the efficacy of a long term rituximab treatment to prevent relapses of ANCA-associated vasculitis in patients in remission after a first phase of rituximab maintenance treatment.

The investigators will conduct a randomized placebo-controlled trial of a long term rituximab maintenance treatment (46 months) against a conventional maintenance treatment (18 months).

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
500 mg rituximab infusion at the randomization visit and every 6 months for 18 months
500 mg rituximab infusion at the randomization visit and every 6 months for 18 months. Each infusion will be preceded by an infusion of 1000 mg paracetamol, 100 mg methylprednisolone and 5 mg dexchlorpheniramine.
(Placebo Comparator)
Placebo infusion at the randomization visit and every 6 months for 18 months

Primary Outcomes

Vasculitis score 2003 (BVAS 2003 )
time frame: 28 months

Secondary Outcomes

Number of adverse events,
time frame: 28 months
number of patients experiencing at least one adverse event in both arms
time frame: 28 months
correlation of ANCA level with the clinical events
time frame: 28 months
ANCA level during follow-up
time frame: 28 months
correlation B-Lymphocytes CD-19 level with the clinical events
time frame: 28 months
B-Lymphocytes CD-19 level during follow-up
time frame: 28 months
number of B memory cells during follow-up in both arms
time frame: 28 months
correlation number of B memory cells with the clinical events
time frame: 28 months
Number of patients with ANCA in each arm
time frame: 28 months
Time frame to death in both arms
time frame: 28 months
time frame of first minor relapse
time frame: 28 months
time frame of first major relapse
time frame: 28 months
Cumulated dose of corticosteroid treatment
time frame: 28 months
Number and severity of damages
time frame: 28 months
number of of gammaglobulins
time frame: 28 months
Quality of life : SF36 (The Short Form (36) Health Survey)
time frame: 28 months
functional capacities : HAQ (Health Assessment Questionnaire )
time frame: 28 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: First, patients must have been included in MAINRITSAN 2 and in addition to meeting the criteria for inclusion and non-inclusion. MAINRITSAN 2 inclusion criteria: - Granulomatosis with Polyangiitis Or microscopic polyangiitis complying Or kidney-limited disease With or without detectable ANCA (anti-neutrophil cytoplasmic antibodies) at the time of diagnosis or relapse, and at remission. - Who have achieved remission using a treatment combining corticosteroids and an immunosuppressive agent, including corticosteroids, cyclophosphamide IV or oral (the use of another immunosuppressant is allowed, according to the current French guidelines, as well as plasma exchanges and/or IV immunoglobulins, or rituximab). - Interval of 1 month between the end of the immunosuppressant treatment and the randomization time if cyclophosphamide or methotrexate were used, interval between 4 and 6 months if rituximab was used - Age > 18 years without age limit higher when the diagnosis is confirmed. - Informed and having signed the consent form to take part in the study. and Patients must meet all of the following criteria: - In complete remission (BVAS 0) at 28 months of MAINRITSAN2 study. - Informed patient who accepted to participate in MAINRITSAN 2 and who signed the informed consent to this extension. - Randomized on the day of the evaluation of the primary endpoint of MAINRITSAN 2 during the visit M28 (last visit of the protocol). Exclusion Criteria: - Eosinophilic granulomatosis with polyangiitis (EGPA) - History of severe allergic manifestations or anaphylactic manifestations following humanized or murine monoclonal antibodies infusions - Pregnant or breast feeding women. Contraception is required for women who could be pregnant during treatment follow up and during the year following the last infusion. - Infection by HIV (positive serology), HCV (positive serology), or HBV (HBsAg positive or anti-HBc antibody positive with anti-HBs antibody negative) - Uncontrolled infection at time of inclusion in the extended follow-up study. - Other severe bacterial, viral , mycobacterial or fungal infection(s), occurring within the last 3 months before of randomization. A severe infection is defined by the hospitalization, a life or organ threatening. - Severe chronic obstructive bronchopathy (FEV < 50% or dyspnea stage III). - Cardiac failure, stage IV according to the NYHA classification. - Recent history of coronary artery disease (<1 month). - Ongoing malignancy or hematologic disease within 5 years before inclusion. - Patient with severe immunodepression characterized by clinical manifestations. - Participation to another concomitant therapeutic study (except observational studies or studies without therapeutic intervention). - Psychiatric disease that may interfere with the study. - Non affiliation to a health insurance. - Uncontrolled severe cardiac disease.

Additional Information

Official title Extended Follow Up of the Mainritsan 2 Study. Comparison Between a Long Term and a Conventional Maintenance Treatment With Rituximab: a Placebo- Controlled Randomized Trial
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Assistance Publique - Hôpitaux de Paris.