- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02433522
Comparison Between a Long Term and a Conventional Maintenance Treatment With Rituximab (MAINRITSAN3)
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
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follow-up study of MAINRITSAN, up to 30% of patients experienced a relapse 38 months after the last rituximab infusion (unpublished data).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).
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Paris, France, 75014
- Hôpital COCHIN
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Rituximab
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
Placebo infusion at the randomization visit and every 6 months for 18 months
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Vasculitis score 2003 (BVAS 2003 )
Time Frame: 28 months
|
Relapse free survival rates (BVAS > 0)
|
28 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of adverse events,
Time Frame: 28 months
|
adverse events including infectious effects and their severity in each arm
|
28 months
|
number of patients experiencing at least one adverse event in both arms
Time Frame: 28 months
|
28 months
|
|
correlation of ANCA level with the clinical events
Time Frame: 28 months
|
28 months
|
|
ANCA level during follow-up
Time Frame: 28 months
|
28 months
|
|
correlation B-Lymphocytes CD-19 level with the clinical events
Time Frame: 28 months
|
28 months
|
|
B-Lymphocytes CD-19 level during follow-up
Time Frame: 28 months
|
28 months
|
|
number of B memory cells during follow-up in both arms
Time Frame: 28 months
|
28 months
|
|
correlation number of B memory cells with the clinical events
Time Frame: 28 months
|
28 months
|
|
Number of patients with ANCA in each arm
Time Frame: 28 months
|
28 months
|
|
Time frame to death in both arms
Time Frame: 28 months
|
28 months
|
|
time frame of first minor relapse
Time Frame: 28 months
|
28 months
|
|
time frame of first major relapse
Time Frame: 28 months
|
"the reappearance of disease activity or worsening, with a Birmingham Vasculitis Activity Score >0, and involvement of one or more major organs, disease-related life-threatening events, or both"
|
28 months
|
Cumulated dose of corticosteroid treatment
Time Frame: 28 months
|
28 months
|
|
Number and severity of damages
Time Frame: 28 months
|
28 months
|
|
number of of gammaglobulins
Time Frame: 28 months
|
28 months
|
|
Quality of life : SF36 (The Short Form (36) Health Survey)
Time Frame: 28 months
|
28 months
|
|
functional capacities : HAQ (Health Assessment Questionnaire )
Time Frame: 28 months
|
28 months
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Loic GUILLEVIN, MD-PhD, Assistance Publique - Hôpitaux de Paris
Publications and helpful links
General Publications
- Pagnoux C, Guillevin L; French Vasculitis Study Group; MAINRITSAN investigators. Rituximab or azathioprine maintenance in ANCA-associated vasculitis. N Engl J Med. 2015 Jan 22;372(4):386-7. doi: 10.1056/NEJMc1414728. No abstract available.
- Charles P, Perrodeau E, Samson M, Bonnotte B, Neel A, Agard C, Huart A, Karras A, Lifermann F, Godmer P, Cohen P, Hanrotel-Saliou C, Martin-Silva N, Pugnet G, Maurier F, Sibilia J, Carron PL, Gobert P, Meaux-Ruault N, Le Gallou T, Vinzio S, Viallard JF, Hachulla E, Vinter C, Puechal X, Terrier B, Ravaud P, Mouthon L, Guillevin L; French Vasculitis Study Group. Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Trial. Ann Intern Med. 2020 Aug 4;173(3):179-187. doi: 10.7326/M19-3827. Epub 2020 Jun 2.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Autoimmune Diseases
- Systemic Vasculitis
- Vasculitis
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- P110146 extended
- 2012-001963-66 (EUDRACT_NUMBER)
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