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

NCT03906227 | Terminated Results DMC FDA Device

• 2 other identifiers: 18-20155P01DK058335-18
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

ANCA Associated Vasculitis

Outcome Measures

Primary Outcomes (1)

• 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 (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 Outcomes (7)

• Number of Participants Who Experience Relapse

  from complete remission to end of study, approximately 2 years

• Frequency of Relapse

  from complete remission to end of study, approximately 2 years

• Severity of Relapse

  from complete remission to end of study, approximately 2 years

• Time to Positive ANCA

  from first negative ANCA test since start of study , if applicable- to end of study, maximum two years, as applicable

• Frequency of Infections

  from remission to end of study, approximately 2 years

Study Arms (3)

low CD5+ /on maintenance

ACTIVE COMPARATOR

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

Device: ENUMERATION OF CD5+ B Cells

high CD5/ on maintenance

ACTIVE COMPARATOR

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

Device: ENUMERATION OF CD5+ B Cells

high CD5 / NO maintenance

EXPERIMENTAL

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

Device: ENUMERATION OF CD5+ B Cells

Interventions

ENUMERATION OF CD5+ B Cells 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; high CD5/ on maintenance; low CD5+ /on maintenance

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7155, United States

Location

Related Publications (1)

• 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.

  PMID: 25372085 RESULT

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Anne Froment
• Organization: University of North Carolina at Chapel Hill

anne_froment@med.unc.edu

919-445-2622

Study Officials

• Vimal Derebail, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects with normalized CD5+ B cells are thought to be at lower risk and relapse, and therefore may not need maintenance immunosuppression. The subjects in that group will be randomized to either maintenance immunosuppression vs close clinical observation without maintenance immunosuppression.

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: April 8, 2019
• Study Start: June 28, 2019
• Primary Completion: February 27, 2025
• Study Completion: February 27, 2025
• Last Updated: November 26, 2025
• Results First Posted: November 26, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 9 to 36 months following publication
• Access Criteria: approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and data use/sharing agreement with UNC.

Locations

US (1)