- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01731561
Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis (MAINRITSAN 2)
March 1, 2018 updated by: Assistance Publique - Hôpitaux de Paris
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.
Study Overview
Status
Completed
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
166
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Paris, France, 75014
- Cochin Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Exclusion Criteria:
- 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
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Rituximab infusion according biological parameters
Rituximab infusion based on ANCA and CD19 lymphocytes
|
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.
|
ACTIVE_COMPARATOR: Systematic rituximab infusion
Semestrial rituximab infusion until 18 months
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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at 28 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients with ANCA (Anti-Neutrophil Cytoplasmatic Antibodies)
Time Frame: at 28 months
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Number of patients with ANCA in each group
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at 28 months
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Number of adverse events
Time Frame: at 28 months
|
To assess the number of adverse events and their severity in each group
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at 28 months
|
Mortality rate
Time Frame: at 28 months
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To assess mortality rate in each group
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at 28 months
|
Number of minor relapse
Time Frame: at 28 months
|
number of minor relapse in each group
|
at 28 months
|
Cumulated dose of corticosteroid treatment
Time Frame: at 28 months
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Cumulated dose of corticosteroid treatment in each group at 28 months
|
at 28 months
|
Number and severity of damages
Time Frame: at 28 months
|
Number and severity of damages in each group
|
at 28 months
|
Evolution of ANCA and the link of the clinical events
Time Frame: at 28 months
|
Evolution of ANCA in each group and the link of the clinical events
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at 28 months
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Distribution of events by severity
Time Frame: at 28 months
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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).
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at 28 months
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Length of corticosteroid treatment
Time Frame: at 28 months
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The length of corticosteroid treatment in each group at 28 months
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at 28 months
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Rate of B-Lymphocytes CD-19 and the link of the clinical events
Time Frame: at 28 months
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The rate of B-Lymphocytes CD-19 and the link of the clinical events
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at 28 months
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Evolution of gammaglobulins
Time Frame: at 28 months
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at 28 months
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Quality of life : SF36 (The Short Form (36) Health Survey)
Time Frame: at 28 months
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at 28 months
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Functional capacities : HAQ (Health Assessment Questionnaire)
Time Frame: at 28 months
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at 28 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Chair: Loic Guillevin, MD, PhD, Cochin Hospital, Paris, France
- Study Chair: Pierre Charles, MD, Institut mutualiste, Paris, France
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
November 16, 2012
Primary Completion (ACTUAL)
April 5, 2016
Study Completion (ACTUAL)
April 5, 2016
Study Registration Dates
First Submitted
October 12, 2012
First Submitted That Met QC Criteria
November 16, 2012
First Posted (ESTIMATE)
November 22, 2012
Study Record Updates
Last Update Posted (ACTUAL)
March 2, 2018
Last Update Submitted That Met QC Criteria
March 1, 2018
Last Verified
February 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Respiratory Tract Diseases
- Immune System Diseases
- Autoimmune Diseases
- Lung Diseases
- Lung Diseases, Interstitial
- Cerebral Small Vessel Diseases
- Vasculitis
- Granulomatosis with Polyangiitis
- Microscopic Polyangiitis
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
- Systemic Vasculitis
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- P110146
- 2012-001963-66 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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