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| ID | Type | Description | Link |
|---|---|---|---|
| AVATARS | Other Identifier | Immune Tolerance Network |
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Slow accrual
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| Name | Class |
|---|---|
| Immune Tolerance Network (ITN) | NETWORK |
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The goal of the study is to find biological markers (certain proteins or cellular markers found in a blood test) that will inform doctors which patients diagnosed with ANCA-associated vasculitis (AAV) are most likely to be able to stop their medications suppressing their immune systems and remain in remission.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are small vessel vasculitides that typically follow a chronic course and are associated with serious illness and death.Three clinical conditions are recognized: microscopic polyangiitis (MPA); granulomatosis with polyangiitis (Wegener's, GPA); and eosinophilic granulomatosis with polyangiitis (EPA, formerly Churg Strauss Syndrome). Though these conditions have different clinical features, they can have overlapping immunological characteristics.
The precise cause of AAV is not understood, but there are clear genetic associations which, in the context of predisposing environmental factors, such as infections, may lead to development of disease. There are no diagnostic criteria for AAV, but there are validated classification criteria and disease definitions.
There is a need to find biological markers that define immunological tolerance so that immunotherapy medicines may be correctly changed and safely withdrawn in some people.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tolerant AAV | Tolerant participants with AAV |
| |
| Non-Tolerant AAV | Non-Tolerant participants with ANCA-associated vasculitis (AAV) |
| |
| Healthy Controls | Healthy participants that fulfill eligibility criteria -similar in age to Tolerant and Non-Tolerant AAV participants. |
| |
| AAV Discontinuing Immunosuppression | Participants have been in clinical remission and on minimal maintenance therapy for at least 2 years prior to screening. Their primary physicians have planned to discontinue immunosuppression medication in the next year after screening. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Venipuncture for blood sample collection | Procedure | Analysis samples from the blood sample collection at specific time points. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Tolerance Biomarker Identification | Identification of biomarkers associated with clinical tolerance in patients with ANCA-associated vasculitis by comparative immunophenotyping of individual leukocyte subsets from tolerant and non-tolerant patients with AAV. Due to early study termination, data was not available to evaluate this endpoint. | Difference from baseline to week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Tolerance Signature Stability | Measurement of the stability of a tolerance immune signature in patients with AAV over time. Due to early study termination, data was not available to evaluate this endpoint. | Baseline to Week 26 |
| Tolerance Signature Versus Clinical Status |
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Inclusion Criteria:
Tolerant AAV participants:
Non-Tolerant AAV participants:
Age 18 years or older
Diagnosis of granulomatosis with polyangiitis (Wegener's), GPA or microscopic polyangiitis (MPA) according to the definitions of the CHCC
History of being MPO-ANCA positive during a disease flare
Within the past 5 years, must have had a disease exacerbation, defined as an increase in the BVAS/WG score and re-institution of immunosuppressive therapy after therapy had been reduced or completely discontinued
In clinical remission with BVAS/WG = 0 and on minimal maintenance therapy for ≥3 months prior to the screening visit. Minimal maintenance therapy is defined as:
Low-dose glucocorticoids (≤10 mg of prednisone or prednisolone daily) and/or:
Positive MPO-ANCA by ELISA on at least 2 occasions within the last 52 weeks, the most recent result being within 8 weeks of visit -1
For women of child-bearing potential, a negative urine or serum pregnancy test at the time of screening
Ability to sign and understand informed consent
Willingness to comply with study procedures.
Healthy Controls:
Exclusion Criteria:
Tolerant AAV Participants:
Non-Tolerant AAV participants:
Healthy Controls:
AAV Participants Discontinuing Immunosuppression:
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Non-tolerant: Patients who have persistently active disease. Tolerant: Those patients who have become ANCA negative, having been ANCA positive at the time of their acute presentation but have been in prolonged disease- free remission off all immunotherapy for at least two years. Healthy controls: Individuals with similar age distribution to participants in the Non-tolerant and Tolerant cohorts.
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| Name | Affiliation | Role |
|---|---|---|
| Alan Salama, MD | University College London, Centre for Nephrology | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Addenbrooke's Hospital | Cambridge | England | CB2 0QQ | United Kingdom | ||
| University College London, Centre for Nephrology |
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| Label | URL |
|---|---|
| The National Institute of Allergy and Infectious Diseases | View source |
| Immune Tolerance Network (ITN) | View source |
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Participants diagnosed with granulomatosis with polyangiitis (Wegener's, GPA) or microscopic polyangiitis, and a history positive for the presence of MPO-ANCA+ during disease flares were recruited for 3 cohorts; healthy participants were recruited for 1 cohort. Participants were recruited from 3 sites in Great Britain from Dec 2013 to Feb 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tolerant AAV | Subjects in the Tolerant ANCA-associated vasculitis (AAV) cohort have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and have been off all immunosuppression medications for at least 2 years prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. |
| FG001 | Non-Tolerant AAV | Subjects in the Non-Tolerant ANCA-associated vasculitis (AAV) cohort have had a disease exacerbation and re-institution of immunosuppressive therapy in the past 5 years. Subjects have also been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and on minimal maintenance therapy for at least 3 months prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. |
| FG002 | Healthy Controls | Healthy participants without autoimmune disease. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. |
| FG003 | AAV Discontinuing Immunosuppression | Subjects in the ANCA-associated vasculitis (AAV) Discontinuing Immunosuppression group have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis BVAS/WG) scores of zero and on minimal maintenance therapy for at least 2 years prior to screening. The subjects' primary physicians have planned to discontinue immunosuppression medication in the next year after screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and at 8 weeks after discontinuation of immunosuppression medication. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The baseline analysis population is defined as all participants who have undergone the Week 0 blood sample collection
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| ID | Title | Description |
|---|---|---|
| BG000 | Tolerant AAV | Subjects in the Tolerant ANCA-associated vasculitis (AAV) cohort have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and have been off all immunosuppression medications for at least 2 years prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. |
| 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 | Tolerance Biomarker Identification | Identification of biomarkers associated with clinical tolerance in patients with ANCA-associated vasculitis by comparative immunophenotyping of individual leukocyte subsets from tolerant and non-tolerant patients with AAV. Due to early study termination, data was not available to evaluate this endpoint. | No analyses were performed due to slow enrollment and early study closure. | Posted | Difference from baseline to week 26 |
|
Subjects in Tolerant AAV, Non-Tolerant AAV, Healthy Controls were followed though Week 26. Subjects in Discontinuation group were followed until 8 weeks after discontinuing immunosuppression meds anytime between Week 0 and 52, for a max time of 60 weeks
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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 | Tolerant AAV | Subjects in the Tolerant ANCA-associated vasculitis (AAV) cohort have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and have been off all immunosuppression medications for at least 2 years prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. |
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Study termination due to slow enrollment, resulting in no outcome analyses.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research Operations Program | DAIT/NIAID | 301-594-7669 | DAITClinicalTrialsGov@niaid.nih.gov |
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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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| ID | Term |
|---|---|
| D018962 | Phlebotomy |
| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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|
Correlation of possible changes in the tolerance signature with changes in clinical status. Due to early study termination, data was not available to evaluate this endpoint. |
| Baseline to Week 26 |
| Immunosuppression Associated Signature | Definition of an immune signature associated with maintenance immunosuppression. Due to early study termination, data was not available to evaluate this endpoint. | Baseline to 8 Weeks Post-Immunosuppression Withdrawal |
| London |
| England |
| NW32PF |
| United Kingdom |
| Hammersmith Hospital | London | England | W12 0HS | United Kingdom |
| Study Terminated by Sponsor |
|
| BG001 | Non-Tolerant AAV | Subjects in the Non-Tolerant ANCA-associated vasculitis (AAV) cohort have had a disease exacerbation and re-institution of immunosuppressive therapy in the past 5 years. Subjects have also been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and on minimal maintenance therapy for at least 3 months prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. |
| BG002 | Healthy Controls | Healthy participants without autoimmune disease. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. |
| BG003 | AAV Discontinuing Immunosuppression | Subjects in the ANCA-associated vasculitis (AAV) Discontinuing Immunosuppression group have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis BVAS/WG) scores of zero and on minimal maintenance therapy for at least 2 years prior to screening. The subjects' primary physicians have planned to discontinue immunosuppression medication in the next year after screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and at 8 weeks after discontinuation of immunosuppression medication. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Non-Tolerant AAV | Subjects in the Non-Tolerant ANCA-associated vasculitis (AAV) cohort have had a disease exacerbation and re-institution of immunosuppressive therapy in the past 5 years. Subjects have also been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and on minimal maintenance therapy for at least 3 months prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. |
| OG002 | Healthy Controls | Healthy participants without autoimmune disease. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. |
| OG003 | AAV Discontinuing Immunosuppression | Subjects in the ANCA-associated vasculitis (AAV) Discontinuing Immunosuppression group have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis BVAS/WG) scores of zero and on minimal maintenance therapy for at least 2 years prior to screening. The subjects' primary physicians have planned to discontinue immunosuppression medication in the next year after screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and at 8 weeks after discontinuation of immunosuppression medication. |
|
| Secondary | Tolerance Signature Stability | Measurement of the stability of a tolerance immune signature in patients with AAV over time. Due to early study termination, data was not available to evaluate this endpoint. | No analyses were performed due to slow enrollment and early study closure. | Posted | Baseline to Week 26 |
|
|
| Secondary | Tolerance Signature Versus Clinical Status | Correlation of possible changes in the tolerance signature with changes in clinical status. Due to early study termination, data was not available to evaluate this endpoint. | No analyses were performed due to slow enrollment and early study closure. | Posted | Baseline to Week 26 |
|
|
| Secondary | Immunosuppression Associated Signature | Definition of an immune signature associated with maintenance immunosuppression. Due to early study termination, data was not available to evaluate this endpoint. | No analyses were performed due to slow enrollment and early study closure. | Posted | Baseline to 8 Weeks Post-Immunosuppression Withdrawal |
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Non-Tolerant AAV | Subjects in the Non-Tolerant ANCA-associated vasculitis (AAV) cohort have had a disease exacerbation and re-institution of immunosuppressive therapy in the past 5 years. Subjects have also been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) scores of zero and on minimal maintenance therapy for at least 3 months prior to screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. | 0 | 3 | 0 | 3 |
| EG002 | Healthy Controls | Healthy participants without autoimmune disease. Subjects have blood samples and other assessments collected for analysis at Week 0 and Week 26. | 0 | 16 | 0 | 16 |
| EG003 | AAV Discontinuing Immunosuppression | Subjects in the ANCA-associated vasculitis (AAV) Discontinuing Immunosuppression group have been in clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis BVAS/WG) scores of zero and on minimal maintenance therapy for at least 2 years prior to screening. The subjects' primary physicians have planned to discontinue immunosuppression medication in the next year after screening. Subjects have blood samples and other assessments collected for analysis at Week 0 and at 8 weeks after discontinuation of immunosuppression medication. | 0 | 8 | 0 | 8 |
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| D017445 |
| Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013812 | Therapeutics |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |