Tailoring Maintenance Therapy to Cluster of Differentiation 5 Positive (CD5+) Regulatory B Cell Recovery in ANCA Vasculitis

NCT ID: NCT03906227

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-28
• Study Completion Date: 2025-02-27

Brief Summary

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. Cluster of Differentiation 20 (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.

Detailed Description

The goal of this study is to test the hypothesis that, in ANCA vasculitis, use of CD5+ B cells at the time of B cell reconstitution in the peripheral blood can be used to stratify patients between those with low % CD5+ B cells at greater risk of relapse who would need maintenance immunosuppression and those with normalized CD5+ B cells who would be at lower risk of relapse, and therefore may not need maintenance immunosuppression. The latter group will be randomized to either maintenance immunosuppression vs close clinical observation without maintenance immunosuppression. This study is not designed to evaluate the efficacy of new therapies in ANCA vasculitis. The treatment regimen used in the proposed study are routinely used in the treatment of patients with ANCA vasculitis and considered standard-of-care.

Conditions

ANCA Associated Vasculitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

low CD5+ /on maintenance

Subjects in remission with Cluster of Differentiation 19 positive (CD19+) CD5+ lower than 43% will continue on maintenance immunosuppression (Maintenance Therapy Group)- no randomization.

Group Type: ACTIVE_COMPARATOR

ENUMERATION OF CD5+ B Cells

Intervention Type: DEVICE

A blood test is done to assess what percentage of CD5+ is present within CD19+. The result is then used to guide choice of arm.

high CD5/ on maintenance

Subjects in remission with CD19+CD5+ 43% or greater, randomized to continue on maintenance immunosuppression (Maintenance Therapy Group)

Group Type: ACTIVE_COMPARATOR

ENUMERATION OF CD5+ B Cells

Intervention Type: DEVICE

A blood test is done to assess what percentage of CD5+ is present within CD19+. The result is then used to guide choice of arm.

high CD5 / NO maintenance

Subjects in remission with CD19+CD5+ 43% or greater , randomized to NO maintenance immunosuppression (NO Maintenance Therapy Group)

Group Type: EXPERIMENTAL

ENUMERATION OF CD5+ B Cells

Intervention Type: DEVICE

A blood test is done to assess what percentage of CD5+ is present within CD19+. The result is then used to guide choice of arm.

Interventions

ENUMERATION OF CD5+ B Cells

A blood test is done to assess what percentage of CD5+ is present within CD19+. The result is then used to guide choice of arm.

Intervention Type: DEVICE

Eligibility Criteria

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 Birmingham Vasculitis Activity Score (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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vimal Derebail, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 25372085 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

5P01DK058335-18

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18-2015

Identifier Type: -

Identifier Source: org_study_id