Granulomatosis With PolyangiitisPhase 3MAINRITSAN 2NCT01731561
Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis
A Phase 3 study testing Rituximab (Arm B) and Rituximab (Arm A) in people with Granulomatosis With Polyangiitis and Microscopic Polyangiitis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The aim of this study is to assess the efficacy of a rituximab regimen based on rate of ANCA and CD19 lymphocytes for maintenance treatment in systemic ANCA-associated vasculitis: prospective, multicenter, controlled, randomized comparative study of two rituximab regimens: one based on ANCA and CD19 lymphocytes versus… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Granulomatosis With Polyangiitis, Microscopic Polyangiitis, Renal Limited Forms
- What is being tested?
- Rituximab (Arm B) and Rituximab (Arm A)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 166 participants
- Where
- 1 siteFrance
- Study dates
- 16 Nov 2012to 5 Apr 2016
- 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
- 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.
Who cannot join
- Other systemic vasculitis
- Secondary vasculitis (following neoplastic disease or an infection in particular)
- Induction treatment with a regimen not corresponding to that recommended in France.
- Patient who has not achieved remission.
- Incapacity or refusal to understand or sign the informed consent form.
- Incapacity or refusal to adhere to treatment or perform the follow-up examinations required by the study. Non-compliance
Show all 25Show fewer
- Allergy, documented hypersensitivity or contraindication to the study medication (cyclophosphamide, corticosteroids, azathioprine, rituximab)
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
- Pregnancy, breastfeeding. Women of childbearing age must use a reliable method of contraception throughout the duration of immunosuppressive treatment up to 1 year after the last infusion of rituximab
- Infection by HIV, HCV or HBV
- Progressive, uncontrolled infection requiring a prolonged treatment (tuberculosis, HIV infection, etc.).
- Severe infection declared during the 3 months before randomization (CMV, HBV, HHV8, HCV, HIV, tuberculosis).
- Progressive cancer or malignant blood disease diagnosed during the 5 years before the diagnosis of vasculitis. Patients suffering from non-metastatic prostate cancer or those cured of a cancer or a malignant blood disorder for more than 5 years and not taking any antineoplastic agents for more than 5 years may be included.
- Participation in another clinical research protocol during the 4 weeks before inclusion.
- Any medical or psychiatric disorder which, in the investigator's opinion, may prevent the administration of treatment and patient follow-up according to the protocol, and/or which may expose the patient to a too greater risk of an adverse effect.
- No social security
- Churg and Strauss syndrome
- Viral, bacterial or fungic or mycobacterial infection uncontrolled in the 4 weeks before the inclusion
- History of deep tissue infection (fasciitis, osteomyelitis, septic arthritis)in the first year before the inclusion
- History of chronic and severe or recurrent infection or history of preexisting disease predisposing to severe infection
- Severe immunodepression
- Administration of live vaccine in the four weeks before inclusion
- Severe chronic obstructive pulmonary diseases (VEMS < 50 % or dyspnea grade III)
- Chronic heart failure stade III and IV (NYHA)
- History of recent acute coronary syndrome, unrelated to vasculitis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: MAINtenance of Remission Using RITuximab in Systemic ANCA-associated Vasculitis II
The aim of this study is to assess the efficacy of a rituximab regimen based on rate of ANCA and CD19 lymphocytes for maintenance treatment in systemic ANCA-associated vasculitis: prospective, multicenter, controlled, randomized comparative study of two rituximab regimens: one based on ANCA and CD19 lymphocytes versus systematic infusions.
Read the detailed description
Randomized, controlled, national, multicenter, prospective study to compare systematic rituximab infusions (conventional therapy) to rituximab infusion based on rate of ANCA and CD19 lymphocytes in patients with systemic ANCA-associated vasculitis, in remission (achieved with an induction treatment combining corticosteroids and an immunosuppressant after the first flare of the disease (new diagnosis) or after a relapse. Patients will be stratified by first flare (66% of the patients) or relapse (33% of the patients). Patients complying with the inclusion criteria may be included when they are in remission from their vasculitis. Patients will be included at the time of remission and then randomized. They will receive maintenance treatment by 1)2 rituximab infusions mg at D1, D15 then every 6 months until month 18 (i.e. a total of 5 infusions), at the dose of 500 mg. 2) 1 rituximab infusion at the dose of 500 mg at D0 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are > to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. After the 18 month length of maintenance phase, i.e. after stopping immunosuppressive maintenance therapy, patients will be followed for an additional 10 month period. Patients with granulomatosis with polyangiitis will be prescribed cotrimoxazole 160/800 tid (for 2 additional years).
- Being tested
- Rituximab (Arm B), Rituximab (Arm A)
- Keywords
- Granulomatosis with Polyangiitis, Microscopic polyangiitis, Renal limited forms, ANCA-associated vasculitis, Rituximab
- Medical subject headings
- Granulomatosis with Polyangiitis, Microscopic Polyangiitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab (Arm B)Drug
Rituximab infusion will be performed at D1 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are > to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis.
Rituximab (Arm A)Drug
Rituximab infusion will be performed at D1, D15, M6, M12 and M18(i.e. a total of 5 infusions), at the dose of 500 mg at a fixed dosage.All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab infusion according biological parameters | Experimental | Rituximab infusion based on ANCA and CD19 lymphocytes Receives: Drug: Rituximab (Arm B) |
| Systematic rituximab infusion | Active comparator | Semestrial rituximab infusion until 18 months Receives: Drug: Rituximab (Arm A) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of relapses
Number of relapses (BVAS>0) majors and minors in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up)
Measured: at 28 months
Secondary outcomes (13)
Number of patients with ANCA (Anti-Neutrophil Cytoplasmatic Antibodies)
Number of patients with ANCA in each group
Measured: at 28 months
Number of adverse events
To assess the number of adverse events and their severity in each group
Measured: at 28 months
Mortality rate
To assess mortality rate in each group
Measured: at 28 months
Number of minor relapse
number of minor relapse in each group
Measured: at 28 months
Cumulated dose of corticosteroid treatment
Cumulated dose of corticosteroid treatment in each group at 28 months
Measured: at 28 months
Number and severity of damages
Number and severity of damages in each group
Measured: at 28 months
Evolution of ANCA and the link of the clinical events
Evolution of ANCA in each group and the link of the clinical events
Measured: at 28 months
Distribution of events by severity
Distribution of events by severity and it will be assigned to the drug and its mode of administration and/or the severity of the disease (in each group).
Measured: at 28 months
Length of corticosteroid treatment
The length of corticosteroid treatment in each group at 28 months
Measured: at 28 months
Rate of B-Lymphocytes CD-19 and the link of the clinical events
The rate of B-Lymphocytes CD-19 and the link of the clinical events
Measured: at 28 months
Evolution of gammaglobulins
Measured: at 28 months
Quality of life : SF36 (The Short Form (36) Health Survey)
Measured: at 28 months
Functional capacities : HAQ (Health Assessment Questionnaire)
Measured: at 28 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2012 (estimated)
- Study start16 Nov 2012
- Primary completion5 Apr 2016
- Study completion5 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Granulomatosis With PolyangiitisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- None (open label)
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Loic Guillevin, MD, PhD, Study chair, Cochin Hospital, Paris, FrancePierre Charles, MD, Study chair, Institut mutualiste, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01731561
- Sponsor's protocol ID
- P110146
- Other IDs
- 2012-001963-66
- Acronym
- MAINRITSAN 2
- Status last verified
- Aug 2025
- First submitted
- 12 Oct 2012
- Last updated
- 5 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Charles P, Terrier B, Perrodeau E, Cohen P, Faguer S, Huart A, Hamidou M, Agard C, Bonnotte B, Samson M, Karras A, Jourde-Chiche N, Lifermann F, Gobert P, Hanrotel-Saliou C, Godmer P, Martin-Silva N, Pugnet G, Matignon M, Aumaitre O, Viallard JF, Maurier F, Meaux-Ruault N, Riviere S, Sibilia J, Puechal X, Ravaud P, Mouthon L, Guillevin L; French Vasculitis Study Group. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann Rheum Dis. 2018 Aug;77(8):1143-1149. doi: 10.1136/annrheumdis-2017-212878. Epub 2018 Apr 25.
PubMed 29695500Khoudour N, Delestre F, Jabot-Hanin F, Jouinot A, Nectoux J, Letouneur F, Izac B, Vidal M, Guillevin L, Puechal X, Charles P, Terrier B, Blanchet B. Association Between Plasma Rituximab Concentration and the Risk of Major Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitides During Rituximab Maintenance Therapy. Arthritis Rheumatol. 2023 Nov;75(11):2003-2013. doi: 10.1002/art.42556. Epub 2023 Aug 13.
PubMed 37134130
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MAINtenance of Remission Using RITuximab in Systemic ANCA-associated Vasculitis II
- ClinicalTrials.gov ID
- NCT01731561
- Acronym / sponsor ID
- MAINRITSAN 2 / P110146
- Keywords
- Granulomatosis with Polyangiitis, Microscopic polyangiitis, Renal limited forms, ANCA-associated vasculitis, Rituximab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 166 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 16 Nov 2012 (actual)
- Primary completion
- 5 Apr 2016 (actual)
- Study completion
- 5 Apr 2016 (actual)
- First posted
- 22 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to assess the efficacy of a rituximab regimen based on rate of ANCA and CD19 lymphocytes for maintenance treatment in systemic ANCA-associated vasculitis: prospective, multicenter, controlled, randomized comparative study of two rituximab regimens: one based on ANCA and CD19 lymphocytes versus systematic infusions.
Detailed description
Randomized, controlled, national, multicenter, prospective study to compare systematic rituximab infusions (conventional therapy) to rituximab infusion based on rate of ANCA and CD19 lymphocytes in patients with systemic ANCA-associated vasculitis, in remission (achieved with an induction treatment combining corticosteroids and an immunosuppressant after the first flare of the disease (new diagnosis) or after a relapse. Patients will be stratified by first flare (66% of the patients) or relapse (33% of the patients). Patients complying with the inclusion criteria may be included when they are in remission from their vasculitis. Patients will be included at the time of remission and then randomized. They will receive maintenance treatment by 1)2 rituximab infusions mg at D1, D15 then every 6 months until month 18 (i.e. a total of 5 infusions), at the dose of 500 mg. 2) 1 rituximab infusion at the dose of 500 mg at D0 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are > to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. After the 18 month length of maintenance phase, i.e. after stopping immunosuppressive maintenance therapy, patients will be followed for an additional 10 month period. Patients with granulomatosis with polyangiitis will be prescribed cotrimoxazole 160/800 tid (for 2 additional years).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab infusion according biological parameters | Experimental | Drug: Rituximab (Arm B)Rituximab infusion based on ANCA and CD19 lymphocytes |
| Systematic rituximab infusion | Active comparator | Drug: Rituximab (Arm A)Semestrial rituximab infusion until 18 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (25 listed)
- Other systemic vasculitis
- Secondary vasculitis (following neoplastic disease or an infection in particular)
- Induction treatment with a regimen not corresponding to that recommended in France.
- Patient who has not achieved remission.
- Incapacity or refusal to understand or sign the informed consent form.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rituximab (Arm B)Rituximab infusion will be performed at D1 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are > to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis. | Drug | Rituximab infusion according biological parameters |
| Rituximab (Arm A)Rituximab infusion will be performed at D1, D15, M6, M12 and M18(i.e. a total of 5 infusions), at the dose of 500 mg at a fixed dosage.All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis. | Drug | Systematic rituximab infusion |
Primary outcome
Number of relapses
Time frame: at 28 months
Number of relapses (BVAS>0) majors and minors in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up)
13 secondary outcomes
Number of patients with ANCA (Anti-Neutrophil Cytoplasmatic Antibodies)
Time frame: at 28 months
Number of adverse events
Time frame: at 28 months
Mortality rate
Time frame: at 28 months
Number of minor relapse
Time frame: at 28 months
Cumulated dose of corticosteroid treatment
Time frame: at 28 months
Number and severity of damages
Time frame: at 28 months
Evolution of ANCA and the link of the clinical events
Time frame: at 28 months
Distribution of events by severity
Time frame: at 28 months
Length of corticosteroid treatment
Time frame: at 28 months
Rate of B-Lymphocytes CD-19 and the link of the clinical events
Time frame: at 28 months
Evolution of gammaglobulins
Time frame: at 28 months
Quality of life : SF36 (The Short Form (36) Health Survey)
Time frame: at 28 months
Functional capacities : HAQ (Health Assessment Questionnaire)
Time frame: at 28 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2025.
- Results publication: PubMed 29695500Charles P, Terrier B, Perrodeau E, Cohen P, Faguer S, Huart A, Hamidou M, Agard C, Bonnotte B, Samson M, Karras A, Jourde-Chiche N, Lifermann F, Gobert P, Hanrotel-Saliou C, Godmer P, Martin-Silva N, Pugnet G, Matignon M, Aumaitre O, Viallard JF, Maurier F, Meaux-Ruault N, Riviere S, Sibilia J, Puechal X, Ravaud P, Mouthon L, Guillevin L; French Vasculitis Study Group. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann Rheum Dis. 2018 Aug;77(8):1143-1149. doi: 10.1136/annrheumdis-2017-212878. Epub 2018 Apr 25.
- Derived from this study: PubMed 37134130Khoudour N, Delestre F, Jabot-Hanin F, Jouinot A, Nectoux J, Letouneur F, Izac B, Vidal M, Guillevin L, Puechal X, Charles P, Terrier B, Blanchet B. Association Between Plasma Rituximab Concentration and the Risk of Major Relapse in Antineutrophil Cytoplasmic Antibody-Associated Vasculitides During Rituximab Maintenance Therapy. Arthritis Rheumatol. 2023 Nov;75(11):2003-2013. doi: 10.1002/art.42556. Epub 2023 Aug 13.
- Website of the French Vasculitis Study GroupLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Loic Guillevin, MD, PhD study chair
Cochin Hospital, Paris, France
Pierre Charles, MD study chair
Institut mutualiste, Paris, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab (Arm B) and Rituximab (Arm A) in people with Granulomatosis With Polyangiitis and Microscopic 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 5 inclusion and 25 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 5 Sep 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?
Number of relapses (time frame: at 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 NCT01731561, which also lists 2 linked publications.
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 5 Sep 2025.