ANCA Associated VasculitisNCT03906227
Tailoring Maintenance Therapy to Cluster of Differentiation 5 Positive (CD5+) Regulatory B Cell Recovery in ANCA Vasculitis
A study testing ENUMERATION OF CD5+ B Cells in people with ANCA Associated Vasculitis, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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" . Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- ANCA Associated Vasculitis
- What is being tested?
- ENUMERATION OF CD5+ B Cells
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jun 2019to 27 Feb 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599-7155
About this study
Official title: 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. 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.
Read the 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
- Being tested
- ENUMERATION OF CD5+ B Cells
- Medical subject headings
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ENUMERATION OF CD5+ B CellsDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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) Receives: 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) Receives: Device: ENUMERATION OF CD5+ B Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: from complete remission to end of study, approximately 2 years
Secondary outcomes (7)
Number of Participants Who Experience Relapse
Relapse in each group was determined using the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis(BVAS, range 0-64). The total score is composed of 34 predefined items grouped into 9 organ systems. Each item has a specified weight of either 3 or 1, depending on whether it reflects major or minor disease activity. A score of 0 indicates no disease activity; a higher score indicates worsening disease. Per protocol relapse is defined as BVAS >/= 2; however for reporting purposes relapse was defined as BVAS >/= 1 because the participant was treated based on the clinical relapse.
Measured: from complete remission to end of study, approximately 2 years
Frequency of Relapse
Frequency, as determined by number of relapse in each group. Per protocol relapse is defined as BVAS >/= 2; however for reporting purposes relapse was defined as BVAS >/= 1 because the participant was treated based on the clinical relapse.
Measured: from complete remission to end of study, approximately 2 years
Severity of Relapse
Severity of relapse as determined by number of major relapse in each group. Major relapse is defined as involving a major organ
Measured: from complete remission to end of study, approximately 2 years
Time to Positive ANCA
For participants who had a negative ANCA test, time to positive ANCA
Measured: from first negative ANCA test since start of study , if applicable- to end of study, maximum two years, as applicable
Frequency of Infections
Frequency as determined by the number of infections
Measured: from remission to end of study, approximately 2 years
Number of Infections, Categorized by Severity
number of mild/moderate/severe infections
Measured: from remission to end of study, approximately 2 years
Time to Interleukin (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
Measured: from enrollment to end of study, approximately 2.5 to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2019
- Study start28 Jun 2019
- Primary completion27 Feb 2025
- Study completion27 Feb 2025
Why it stopped: Study recruitment terminated due to lack of funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ANCA Associated VasculitisStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vimal Derebail, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03906227
- Sponsor's protocol ID
- 18-2015
- Other IDs
- 5P01DK058335-18
- Status last verified
- May 2025
- First submitted
- 4 Apr 2019
- Last updated
- 26 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 25372085
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tailoring Maintenance Therapy to CD5+ Regulatory B Cell Recovery in ANCA Vasculitis
- ClinicalTrials.gov ID
- NCT03906227
- Acronym / sponsor ID
- 18-2015
- Conditions
- ANCA Associated Vasculitis
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study recruitment terminated due to lack of funding.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 28 Jun 2019 (actual)
- Primary completion
- 27 Feb 2025 (actual)
- Study completion
- 27 Feb 2025 (actual)
- First posted
- 8 Apr 2019 (actual)
- Results
- Posted 26 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| low CD5+ /on maintenance | Active comparator | Device: ENUMERATION OF CD5+ B CellsSubjects in remission with Cluster of Differentiation 19 positive (CD19+) CD5+ lower than 43% will continue on maintenance immunosuppression (Maintenance Therapy Group)- no randomization. |
| high CD5/ on maintenance | Active comparator | Device: ENUMERATION OF CD5+ B CellsSubjects in remission with CD19+CD5+ 43% or greater, randomized to continue on maintenance immunosuppression (Maintenance Therapy Group) |
| high CD5 / NO maintenance | Experimental | Device: ENUMERATION OF CD5+ B CellsSubjects in remission with CD19+CD5+ 43% or greater , randomized to NO maintenance immunosuppression (NO Maintenance Therapy Group) |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ENUMERATION OF CD5+ B CellsA blood test is done to assess what percentage of CD5+ is present within CD19+. The result is then used to guide choice of arm. | Device | high CD5 / NO maintenance, high CD5/ on maintenance, low CD5+ /on maintenance |
Primary outcome
Time to First Relapse
Time frame: from complete remission to end of study, approximately 2 years
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.
7 secondary outcomes
Number of Participants Who Experience Relapse
Time frame: from complete remission to end of study, approximately 2 years
Frequency of Relapse
Time frame: from complete remission to end of study, approximately 2 years
Severity of Relapse
Time frame: from complete remission to end of study, approximately 2 years
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
Frequency of Infections
Time frame: from remission to end of study, approximately 2 years
Number of Infections, Categorized by Severity
Time frame: from remission to end of study, approximately 2 years
Time to Interleukin (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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25372085Guillevin 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vimal Derebail, MD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ENUMERATION OF CD5+ B Cells in people with ANCA Associated Vasculitis, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to First Relapse (time frame: from complete remission to end of study, approximately 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03906227, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2025.