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| ID | Type | Description | Link |
|---|---|---|---|
| 5P01DK058335-18 | U.S. NIH Grant/Contract | View source |
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Study recruitment terminated due to lack of funding.
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| high CD5/ on maintenance | Active Comparator | Subjects in remission with CD19+CD5+ 43% or greater, randomized to continue on maintenance immunosuppression (Maintenance Therapy Group) |
|
| high CD5 / NO maintenance | Experimental | Subjects in remission with CD19+CD5+ 43% or greater , randomized to NO maintenance immunosuppression (NO Maintenance Therapy Group) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vimal Derebail, MD | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599-7155 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25372085 | Result | 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. |
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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.
9 to 36 months following publication
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.
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Individuals who signed informed consent and then completed all baseline measurement procedures and remained eligible were considered enrolled and were randomized. One consented participant experienced a Serious Adverse Event and was withdrawn before randomization and another consented participant was screen failed because they were not in remission.
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| ID | Title | Description |
|---|---|---|
| FG000 | Low CD5+ /on Maintenance | Participants in remission with Cluster of Differentiation (CD)19+CD5+ lower than 43% will continue on maintenance immunosuppression (Maintenance Therapy Group)- no randomization. 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. |
| FG001 | High CD5/ on Maintenance | Participants in remission with Cluster of Differentiation 19 positive (CD19+)CD5+ 43% or greater, randomized to continue on maintenance immunosuppression (Maintenance Therapy Group) 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. |
| FG002 | High CD5 / NO Maintenance | Participants in remission with CD19+CD5+ 43% or greater , randomized to NO maintenance immunosuppression (NO Maintenance Therapy Group) 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Low CD5+ /on Maintenance | Participants in remission with Cluster of Differentiation (CD)19+CD5+ lower than 43% will continue on maintenance immunosuppression (Maintenance Therapy Group)- no randomization. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 (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. | Posted | Mean | Standard Deviation | months | from complete remission to end of study, approximately 2 years |
|
From the time of signing informed consent through study completion, up to 2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Low CD5+ /on Maintenance | Participants in remission with Cluster of Differentiation (CD)19+CD5+ lower than 43% will continue on maintenance immunosuppression (Maintenance Therapy Group)- no randomization. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intracranial mass | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Prolonged fatigue | General disorders | Systematic Assessment | Post Rituxan infusion |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anne Froment | University of North Carolina at Chapel Hill | 919-445-2622 | anne_froment@med.unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 22, 2024 | Nov 4, 2025 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 12, 2025 | Aug 12, 2025 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D056648 | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis |
| ID | Term |
|---|---|
| D056647 | Systemic Vasculitis |
| D014657 | Vasculitis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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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.
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| 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. | 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 | 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 | 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 | from remission to end of study, approximately 2 years |
| Number of Infections, Categorized by Severity | number of mild/moderate/severe infections | 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 | from enrollment to end of study, approximately 2.5 to 3 years |
| BG001 |
| High CD5/ on Maintenance |
Participants in remission with CD19+CD5+ 43% or greater, randomized to continue on maintenance immunosuppression (Maintenance Therapy Group) 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. |
| BG002 | High CD5 / NO Maintenance | Participants in remission with CD19+CD5+ 43% or greater , randomized to NO maintenance immunosuppression (NO Maintenance Therapy Group) 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. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Anti-Neutrophilic Cytoplasmic Antibodies (ANCA) Positive at Enrollment | Count of Participants | Participants |
|
| OG001 | High CD5/ on Maintenance | Participants in remission with CD19+CD5+ 43% or greater, randomized to continue on maintenance immunosuppression (Maintenance Therapy Group) 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. |
| OG002 | High CD5 / NO Maintenance | Participants in remission with CD19+CD5+ 43% or greater , randomized to NO maintenance immunosuppression (NO Maintenance Therapy Group) 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. |
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | from complete remission to end of study, approximately 2 years |
|
|
|
| Secondary | 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. | Posted | Number | relapse | from complete remission to end of study, approximately 2 years |
|
|
|
| Secondary | 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 | Posted | Count of Participants | Participants | from complete remission to end of study, approximately 2 years |
|
|
|
| Secondary | Time to Positive ANCA | For participants who had a negative ANCA test, time to positive ANCA | Posted | Mean | Standard Deviation | months | from first negative ANCA test since start of study , if applicable- to end of study, maximum two years, as applicable |
|
|
|
| Secondary | Frequency of Infections | Frequency as determined by the number of infections | Posted | Number | infections | from remission to end of study, approximately 2 years |
|
|
|
| Secondary | Number of Infections, Categorized by Severity | number of mild/moderate/severe infections | Posted | Number | infection | from remission to end of study, approximately 2 years |
|
|
|
| Secondary | 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 | Posted | Mean | Standard Deviation | months | from enrollment to end of study, approximately 2.5 to 3 years |
|
|
|
| 0 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | High CD5/ on Maintenance | Participants in remission with CD19+CD5+ 43% or greater, randomized to continue on maintenance immunosuppression (Maintenance Therapy Group) 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. | 0 | 4 | 0 | 4 | 1 | 4 |
| EG002 | High CD5 / NO Maintenance | Participants in remission with CD19+CD5+ 43% or greater , randomized to NO maintenance immunosuppression (NO Maintenance Therapy Group) 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. | 0 | 2 | 0 | 2 | 2 | 2 |
| EG003 | Non-Randomized | Participants who signed informed consent but could not be randomized. | 0 | 2 | 1 | 2 | 0 | 2 |
| Pruritic rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Reaction to Shingrix vaccination | Immune system disorders | Systematic Assessment |
|
| Syncopal episode resulting in fall with head trauma | Cardiac disorders | Systematic Assessment |
|
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Periorbital cellulitis | Infections and infestations | Systematic Assessment |
|
| Right knee swollen and hot to touch | Musculoskeletal and connective tissue disorders | Systematic Assessment | Similar to gout flare symptoms |
|
| Increase in right hydrocele | Reproductive system and breast disorders | Systematic Assessment |
|
| Bilateral leg weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Right knee pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Belching | Gastrointestinal disorders | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
|
| Fracture of left radius | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Abnormal urinalysis | Renal and urinary disorders | Systematic Assessment |
|
| Iron deficiency | Blood and lymphatic system disorders | Systematic Assessment |
|
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Tendon nodules | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| "Trigger finger" | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Pain at vaccination site | General disorders | Systematic Assessment |
|
| Small left eye hemorrhage at inner area | Eye disorders | Systematic Assessment |
|
| Heart burn when lying down | Gastrointestinal disorders | Systematic Assessment |
|
| Squamous cell carcinoma skin lesion on right arm above elbow-removed | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Further removal of squamous cell carcinoma on right arm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Right foot Planter's wart removal | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rotator cuff tear left shoulder | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Increased arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Lower back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment | Subsequent to shingles vaccine |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Pain from frozen shoulder | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Low vitamin B | Metabolism and nutrition disorders | Systematic Assessment |
|
| rituximab infusion reaction | Immune system disorders | Systematic Assessment |
|
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| D017445 |
| Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Title | Measurements |
|---|---|
|
| No relapse |
|
| Moderate |
|
| Severe |
|