- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03906227
Tailoring Maintenance Therapy to Cluster of Differentiation 5 Positive (CD5+) Regulatory B Cell Recovery in ANCA Vasculitis
February 28, 2024 updated by: University of North Carolina, Chapel Hill
Tailoring Maintenance Therapy to CD5+ Regulatory B Cell Recovery in ANCA Vasculitis
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.
Study Overview
Status
Suspended
Conditions
Intervention / Treatment
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 and 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.
Study Type
Interventional
Enrollment (Estimated)
40
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Caroline Poulton
- Phone Number: (919) 445-2636
- Email: Caroline_jennette@med.unc.edu
Study Locations
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North Carolina
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Chapel Hill, North Carolina, United States, 27599-7155
- University of North Carolina at Chapel Hill
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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 to 85 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
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 Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: low CD5+ /on maintenance
Subjects in remission with Cluster of Differentiation (CD)19+CD5+ lower than 43% will continue on maintenance immunosuppression (Maintenance Therapy Group)- no randomization.
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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.
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Active Comparator: high CD5/ on maintenance
Subjects in remission with CD19+CD5+ 43% or greater, randomized to continue on maintenance immunosuppression (Maintenance Therapy Group)
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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.
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Experimental: high CD5 / NO maintenance
Subjects in remission with CD19+CD5+ 43% or greater , randomized to NO maintenance immunosuppression (NO Maintenance Therapy Group)
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to First Relapse
Time Frame: from complete remission to end of study, approximately 2 years
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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.
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from complete remission to end of study, approximately 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Severity of Relapse
Time Frame: from complete remission to end of study, approximately 2 years
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severity (as determined by BVAS score) of relapse in each group
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from complete remission to end of study, approximately 2 years
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Frequency of Relapse
Time Frame: from complete remission to end of study, approximately 2 years
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frequency, as determined by number of relapse in each group
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from complete remission to end of study, approximately 2 years
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Time to Positive ANCA
Time Frame: from first negative ANCA test since start of study , if applicable- to end of study, maximum two years, as applicable
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for patients who had a negative ANCA test, time to positive ANCA
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from first negative ANCA test since start of study , if applicable- to end of study, maximum two years, as applicable
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Frequency of Infections
Time Frame: from remission to end of study, approximately 2 years
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number of infections
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from remission to end of study, approximately 2 years
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Number of Infections, categorized by severity
Time Frame: from remission to end of study, approximately 2 years
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number of mild/moderate/serious infections
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from remission to end of study, approximately 2 years
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Time to IL-10 secreting B regulatory cells > 45% or CD5+ B cells > 43% of total B cells
Time Frame: from enrollment to end of study, approximately 2.5 to 3 years
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time to IL-10 secreting B regulatory cells > 45% or CD5+ B cells > 43% of total B cells
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from enrollment to end of study, approximately 2.5 to 3 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Vimal Derebail, MD, University of North Carolina, Chapel Hill
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.
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)
June 28, 2019
Primary Completion (Estimated)
February 1, 2025
Study Completion (Estimated)
February 1, 2025
Study Registration Dates
First Submitted
April 4, 2019
First Submitted That Met QC Criteria
April 4, 2019
First Posted (Actual)
April 8, 2019
Study Record Updates
Last Update Posted (Estimated)
March 1, 2024
Last Update Submitted That Met QC Criteria
February 28, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18-2015
- 5P01DK058335-18 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
IPD Sharing Time Frame
9 to 36 months following publication
IPD Sharing 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.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
Yes
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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