- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03920722
Efficacy and Safety of Rituximab in the Treatment of Good Prognosis Microscopic Polyangiitis (RITUXGOPRO)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Microscopic polyangiitis (MPA), is a small-sized vessel necrotizing vasculitis associated with anti-neutrophils cytoplasmic antibody (ANCA). Treatment of ANCA associated vasculitis (AAV) was previously based on glucocorticoids (GC) and cyclophosphamide. It has been demonstrated in two prospective randomized trials that rituximab is as effective as cyclophosphamide in the induction treatment of GPA and severe MPA. In addition, it was shown in GPA and MPA that rituximab is superior to azathioprine as maintenance therapy.
Patients with MPA without poor prognosis factor (Five factor score (FFS)=0) have not been included in the previous studies and GC alone is considered as the reference treatment in these patients. However, as much as 50% of these patients experience relapses after a 24 months follow-up and only 40% of patients have a long lasting remission.
In the group of patients with MPA without any poor prognosis factor (FFS=0), an additional treatment with rituximab might decrease the relapse rate from 40% to 15% after an 18 months' follow-up. The efficacy and safety of this proposal must be tested.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Paris, France, 75014
- Cochin Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient (male or female) over 18 year old
- Patient agree to participate in the study and signed written informed consent
- Patient with MPA according to the CHCC established in 2012
- Absence of any poor prognosis factor (modified five factor score (FFS) 1996 = 0)
- Patient with recent onset or relapse of the disease (<1 month) defined by BVAS > 0, who did not received any other treatment than glucocorticoids during last month. For patients with a BVAS<3, activity of vasculitis (either relapse or new onset) has to be confirmed by the coordinating investigator. One to 3 initial glucocorticoids pulse(s) are allowed.
- Patient with anti-MPO antibody measured by enzyme - linked immunosorbent assay (ELISA).
- Negative pregnancy test (serum β-hCG) for women of child-bearing potential and a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study and 12 months after stopping therapy
Exclusion Criteria:
- Small-sized vessels vasculitis not associated to anti-MPO antibody or associated with anti-PR3 positivity.
- Patients with either GPA or EGPA vasculitis according to ACR criteria
- Patient with a modified FFS 1996 ≥ 1
- Patient with alveolar hemorrhage requiring mechanical ventilation
- Patient with previous glucocorticoids treatment >1 month and > 10mg/day either for vasculitis or for any other reason.
Patient already receiving immunosuppressant or biological agent.
Prior treatment with any of the following:
- azathioprine, methotrexate, mycophenolate mophetil, mycophenolic acid within 4 weeks before inclusion
- alkylant agent such as cyclophosphamide within 6 months before inclusion
- anti-TNF inhibitors : infliximab within 8 weeks, adalimumab and etanercept within 2 weeks before inclusion
- anti-CD20 therapy within one year before inclusion.
- Patient with a previous diagnosis of cancer < 5 years (except for in situ cervical cancer and skin carcinoma with R0 resection)
- Patient with acute infections or chronic active infections (HIV, hepatitis B or C)
- Breast feeding woman or woman refusing the use of a contraceptive method for the 18 months' duration of the study
- Contraindication to treatment (glucocorticoids or rituximab)
- Unable to receive written informed consent of patient. Patient unable to understand the protocol
- Patient already in another therapeutic protocol
- Patient without social security
- Patient with severe cardiac failure defined as class IV in New York Heart Association classification or severe, uncontrolled cardiac disease.
- Patients with hypersensitivity to a monoclonal antibody or biological agent.
- Patients in a severely immunocompromised state.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Rituximab
Experimental regimen: One year Glucocorticoid treatment and Rituximab IV 1 gram on Day 1 and 15
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1 gram IV on Day 1 and 15 after premedication with 100 mg méthylprednisolone, 1 gramm paracetamol and 5 mg dexchlorpheniramine
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Placebo Comparator: Rituximab-Placebo
Standard regimen: One-year Glucocorticoid treatment and Placebo-Rituximab IV on Day 1 and 15
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Placebo-Rituximab 1 gram IV on Day 1 and 15 after premedication with 100 mg méthylprednisolone, 1 gramm paracetamol and 5 mg dexchlorpheniramine
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease free survival rate
Time Frame: 18 months
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Failure free survival in patients with microscopic polyangiitis treated with rituximab and glucocorticoids compared to glucocorticoids alone.
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18 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative dose of GC in each group
Time Frame: 18 months
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GC dose will be recorded at each visit
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18 months
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Proportion of patients who achieve a complete remission defined by the absence of sign attributable to vasculitis and a BVAS=0
Time Frame: 1 month
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Absence of sign attributable to vasculitis and a BVAS=0 at M3
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1 month
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Compare proportion of patients who relapse and time to first relapse
Time Frame: 18 months
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Relapse is defined after visit M3 by the reoccurrence of signs or symptoms attributable to vasculitis and a BVAS≥1 or the impossibility to decrease GC therapy according to the predefined protocol
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18 months
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Among patients who relapse, proportion of major relapses
Time Frame: 18 months
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Major relapse is defined by reappearance or worsening of disease with a BVAS≥1 and involvement of at least one major organ, a life-threatening manifestation, or both
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18 months
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Among patients who relapse, proportion of minor relapses
Time Frame: 18 months
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Minor relapse is defined by reappearance or worsening of disease with a BVAS≥1, not corresponding to a major relapse
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18 months
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Mortality rate
Time Frame: 18 months
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Proportion will be compared between groups
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18 months
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Quality of life:Short Form Health Survey Questionnaire (SF-36)
Time Frame: 18 months
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Assessed by mean variation of the SF-36 The 36-Item Short Form Health Survey questionnaire (SF-36) questionnaire includes 36 items related to eight health component (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health.)
A scale has been established for each component and results vary from 0 (bad health perception) to 100 (good health perception).
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18 months
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Disability
Time Frame: 18 months
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Assessed by the mean variation of the Health Assessment Questionnaire (HAQ) Health Assessment Questionnaire (HAQ) is a questionnaire that evaluates the disability of the patient.
Results vary from 0 (no assistance is needed) to 3 (patient usually needs both a special device and help from another person).
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18 months
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Disability
Time Frame: 18 months
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Assessed by the mean variation of the Euroqol 5D (EQ-5D).
The EuroQol-5 dimension (EQ-5D-3L) is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal.
The EQ-5D is made up of five dimensions (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression), each of which can be rated at one of three levels (no problem, some problems, extreme/severe problems).
The EuroQol questionnaire also contains a visual analogue scale (EQ-VAS), where patients are asked to rate their current health state on a 0 (worst imaginable health state) to 100 (best imaginable health state) scale.
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18 months
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Severity of sequels linked to vasculitis as
Time Frame: 18 months
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Assessed by comparison of the VDI score.
The Vascular Damage index score documents any organ damage that has occurred in patients since the onset of vasculitis.
The score includes 64 items that are categorized into 11 groups (by organ system) and result is the summ of each damaged items.
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18 months
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Proportion of patients who still receive GC at the end of follow-up
Time Frame: 18 months
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Proportion will be compared between groups
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18 months
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Number and severity of side effect.
Time Frame: 18 months
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Record of adverse events and serious adverse events related to vasculitis or treatment in each group.
Classification is made according to the CTCAE toxicity grading system.
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18 months
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Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Luc Mouthon, MD PhD, Assistance Publique - Hôpitaux de Paris
Publications and helpful links
General Publications
- Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32. doi: 10.1056/NEJMoa0909905.
- Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaitre O, Cohen P, Maurier F, Decaux O, Ninet J, Gobert P, Quemeneur T, Blanchard-Delaunay C, Godmer P, Puechal X, Carron PL, Hatron PY, Limal N, Hamidou M, Ducret M, Daugas E, Papo T, Bonnotte B, Mahr A, Ravaud P, Mouthon L; French Vasculitis Study Group. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014 Nov 6;371(19):1771-80. doi: 10.1056/NEJMoa1404231.
- Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Fessler BJ, Ding L, Viviano L, Tchao NK, Phippard DJ, Asare AL, Lim N, Ikle D, Jepson B, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Mueller M, Sejismundo LP, Mieras K, Stone JH; RAVE-ITN Research Group. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013 Aug 1;369(5):417-27. doi: 10.1056/NEJMoa1213277.
- Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR; European Vasculitis Study Group. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010 Jul 15;363(3):211-20. doi: 10.1056/NEJMoa0909169.
- Samson M, Puechal X, Devilliers H, Ribi C, Cohen P, Bienvenu B, Ruivard M, Terrier B, Pagnoux C, Mouthon L, Guillevin L; French Vasculitis Study Group (FVSG). Long-term follow-up of a randomized trial on 118 patients with polyarteritis nodosa or microscopic polyangiitis without poor-prognosis factors. Autoimmun Rev. 2014 Feb;13(2):197-205. doi: 10.1016/j.autrev.2013.10.001. Epub 2013 Oct 23.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
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
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Immune System Diseases
- Autoimmune Diseases
- Vasculitis
- Cerebral Small Vessel Diseases
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
- Microscopic Polyangiitis
- Systemic Vasculitis
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- P170909J
- 2018-000637-12 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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