ANCA Associated Vasculitis Clinical Trial
Official title:
Tailoring Maintenance Therapy to CD5+ Regulatory B Cell Recovery in ANCA Vasculitis
Verified date | February 2024 |
Source | University of North Carolina, Chapel Hill |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
ANCA vasculitis is a pauci-immune systemic small vessel vasculitis. The anti-neutrophilic cytoplasmic antibodies (ANCA) are pathogenic and cause disease by activating neutrophils which damage blood vessels. CD means "cluster of differentiation" . CD5 is a type I transmembrane protein found on T cells, thymocytes, and some B cells. CD20 is a type III transmembrane protein found on B cells. The investigators previously detected an association between recovery of Interleukin 10 (IL-10)-secreting CD20+ and CD5+ regulatory B cells after immunotherapy (with rituximab and corticosteroids) and decreased risk of subsequent relapse in patients with ANCA-vasculitis. The investigators hypothesize that patients with complete reconstitution of a functional regulatory B cell repertoire after induction therapy are at low risk of relapse and may be monitored conservatively without further immunotherapy. The investigators will test this hypothesis through a proof of concept randomized controlled study. Patients with normalization of CD5+ regulatory B cells will be randomized to maintenance therapy with rituximab vs. close observation without immunosuppression. Patients whose peripheral CD5+ regulatory B cells remain low after induction therapy (who are at higher risk of relapse), will receive maintenance immunosuppression with rituximab. Patients needing or randomized to maintenance therapy who are unable to receive rituximab will receive azathioprine or mycophenolate mofetil, two standard alternative medications for maintenance immunosuppression.
Status | Suspended |
Enrollment | 40 |
Est. completion date | February 2025 |
Est. primary completion date | February 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 85 Years |
Eligibility | Inclusion Criteria: - Patients 18-85 years old. - ANCA Glomerulonephritis (GN) or vasculitis per Chapel Hill Consensus Criteria, with documented current or previously positive Myeloperoxidase (MPO)- or Proteinase 3 (PR3)-ANCA by ELISA test. Patients with biopsy-proven, pauci-immune crescentic glomerulonephritis are eligible if they have a positive ANCA test by immunofluorescent microscopy (IIFM). - Patients must be in complete remission for at least 1 month and after AT LEAST 3 MONTHS of induction of therapy with corticosteroids and rituximab (either 1000 mg IV x 2 or 375 mg/m2 IV x 4) OR corticosteroids and cyclophosphamide (monthly IV or daily oral doses). They must be on no more than 5 mg daily of oral prednisone or equivalent. Complete remission is defined as a BVAS score = 0. - Patients may be ANCA negative or positive at randomization. - B cells are not depleted anymore: B cell recovery reaches 1% CD19+ B cells (enough to allow determination of CD5+ B cells with confidence). Exclusion Criteria: - Patients who have had = 2 relapses (defined as recurrence of any signs or symptoms attributable to active vasculitis) previously as patients with multiple prior relapses may be at higher risk of future relapse and require maintenance therapy - Patients with persistent low-grade disease activity ("grumbling" disease defined as BVAS > 0 and = 3) - Patients with active systemic infections or deep space infections within the 3 months prior to screening. - Patients participating in another clinical trial mandating maintenance therapy - Patients with drug-induced ANCA vasculitis (e.g. levamisole-adulterated cocaine) - Active tuberculosis, human immunodeficiency virus (HIV), hepatitis C virus or hepatitis B virus infections - For women of child-bearing potential, pregnancy, breastfeeding, unwillingness or inability to comply with effective contraception - Inability to come to scheduled visits |
Country | Name | City | State |
---|---|---|---|
United States | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina |
Lead Sponsor | Collaborator |
---|---|
University of North Carolina, Chapel Hill | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
United States,
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, Ra — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Time to First Relapse | The primary outcome measure is time to first relapse defined as recurrence of any signs or symptoms attributable to active vasculitis after a period of complete remission, with at least 2 minor or 1 major item on the BVAS score (BVAS=2). Per protocol, complete remission is defined as a BVAS score = 0. Birmingham Vasculitis Activity Score for Wegener's Granulomatosis(BVAS, range 0-64). The total score is composed of 34 predefined items, units on a scale, grouped into 9 organ systems. Each item carries a weight from 1-3, depending on disease severity. A score of 0 indicates no disease activity; a higher score indicates worsening disease. | from complete remission to end of study, approximately 2 years | |
Secondary | Severity of Relapse | severity (as determined by BVAS score) of relapse in each group | from complete remission to end of study, approximately 2 years | |
Secondary | Frequency of Relapse | frequency, as determined by number of relapse in each group | from complete remission to end of study, approximately 2 years | |
Secondary | Time to Positive ANCA | for patients who had a negative ANCA test, time to positive ANCA | from first negative ANCA test since start of study , if applicable- to end of study, maximum two years, as applicable | |
Secondary | Frequency of Infections | number of infections | from remission to end of study, approximately 2 years | |
Secondary | Number of Infections, categorized by severity | number of mild/moderate/serious infections | from remission to end of study, approximately 2 years | |
Secondary | Time to IL-10 secreting B regulatory cells > 45% or CD5+ B cells > 43% of total B cells | time to IL-10 secreting B regulatory cells > 45% or CD5+ B cells > 43% of total B cells | from enrollment to end of study, approximately 2.5 to 3 years |
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