ANCA-Associated VasculitisAAVNCT01934504
Defining Immune Tolerance in ANCA-associated Vasculitis (AAV)
An observational study of ANCA-Associated Vasculitis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- ANCA-Associated Vasculitis
- What is being tested?
- Venipuncture for blood sample collection
- Type of treatment
- Surgery or procedure
- How many people
- 33 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Dec 2013to Feb 2015
- Phase
- Observational
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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 Chapel Hill Consensus Conference (CHCC)
- History of being myeloperoxidase (MPO)-ANCA positive during a disease flare
- In clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) = 0 and off all immunosuppression for ≥ 2 years
- Negative MPO-ANCA and proteinase 3 (PR3)-ANCA by ELISA at screening
Show all 27Show fewer
- 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.
- 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:
- Azathioprine ≤ 150mg daily or
- Mycophenolate mofetil (MMF) ≤ 1 gram daily or mycophenolate sodium ≤ 720 mg daily.
- 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:
- Healthy participant age ≥18 years
- 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.
Who cannot join
- Tolerant AAV Participants:
- Use of systemic intravenous (IV) or oral glucocorticoids for ˃ 1 month for any non-vasculitis indication within 8 weeks of the screening visit
- Any prior treatment with rituximab
- Presence of known chronic viral infections or autoimmune diseases
- History of malignancy, excluding non-melanomatous skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit.
- Non-Tolerant AAV participants:
Show all 21Show fewer
- Use of IV pulse glucocorticoids (methylprednisolone or other) or cyclophosphamide within the year prior to the screening visit
- Use of IV or oral glucocorticoids for > 1 month for any non- vasculitis indication within 8 weeks of screening visit
- Any prior treatment with rituximab
- Maintenance therapy with methotrexate within 3 months of the screening visit
- Presence of known chronic viral infections or other autoimmune diseases
- History of malignancy, excluding non-melanoma skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit.
- Healthy Controls:
- Use of IV or oral glucocorticoids for > 1 month for any non-vasculitis indication within 8 weeks of the screening visit
- Presence of known chronic viral infections or other autoimmune diseases
- History of malignancy, excluding non-melanoma skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit.
- AAV Participants Discontinuing Immunosuppression:
- Any prior treatment with rituximab
- Maintenance therapy with methotrexate within 3 months of the screening visit
- Presence of known chronic viral infections or other autoimmune diseases
- History of malignancy, excluding non-melanoma skin cancers or cervical cancer carcinoma in situ, within 5 years of the screening visit.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Addenbrooke's Hospital
Cambridge, England, CB2 0QQ
University College London, Centre for Nephrology
London, England, NW32PF
Hammersmith Hospital
London, England, W12 0HS
About this study
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.
Read the detailed description
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.
- Conditions
- ANCA-Associated Vasculitis
- Being tested
- Venipuncture for blood sample collection
- Keywords
- clinical tolerance, biomarker(s) identification
- 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.
Venipuncture for blood sample collectionProcedure or surgery
Also called Peripheral venous blood draw
Analysis samples from the blood sample collection at specific time points.
| Study group | Role | What they receive |
|---|---|---|
| Tolerant AAV | Tolerant participants with AAV Receives: Procedure: Venipuncture for blood sample collection | |
| Non-Tolerant AAV | Non-Tolerant participants with ANCA-associated vasculitis (AAV) Receives: Procedure: Venipuncture for blood sample collection | |
| Healthy Controls | Healthy participants that fulfill eligibility criteria -similar in age to Tolerant and Non-Tolerant AAV participants. Receives: Procedure: Venipuncture for blood sample collection | |
| 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. Receives: Procedure: Venipuncture for blood sample collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Difference from baseline to week 26
Secondary outcomes (3)
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.
Measured: Baseline to Week 26
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.
Measured: 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.
Measured: Baseline to 8 Weeks Post-Immunosuppression Withdrawal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2013 (estimated)
- Study startDec 2013
- Primary completionFeb 2015
- Study completionFeb 2015
Why it stopped: Slow accrual
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.
- Other trials for ANCA-Associated VasculitisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Responsible party
- Sponsor
- Investigators
- Alan Salama, MD, Study chair, University College London, Centre for Nephrology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01934504
- Sponsor's protocol ID
- DAIT ITN051AI
- Other IDs
- AVATARS
- Acronym
- AAV
- Status last verified
- Apr 2016
- First submitted
- 29 Aug 2013
- Last updated
- 20 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining Immune Tolerance in ANCA-associated Vasculitis (AAV)
- ClinicalTrials.gov ID
- NCT01934504
- Acronym / sponsor ID
- AAV / DAIT ITN051AI
- Conditions
- ANCA-Associated Vasculitis
- Keywords
- clinical tolerance, biomarker(s) identification
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 33 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Study start
- Dec 2013
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 4 Sep 2013 (estimated)
- Results
- Posted 20 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Tolerant AAV | – | Procedure: Venipuncture for blood sample collectionTolerant participants with AAV |
| Non-Tolerant AAV | – | Procedure: Venipuncture for blood sample collectionNon-Tolerant participants with ANCA-associated vasculitis (AAV) |
| Healthy Controls | – | Procedure: Venipuncture for blood sample collectionHealthy participants that fulfill eligibility criteria -similar in age to Tolerant and Non-Tolerant AAV participants. |
| AAV Discontinuing Immunosuppression | – | Procedure: Venipuncture for blood sample collectionParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (27 listed)
- Age 18 years or older
- Diagnosis of granulomatosis with polyangiitis (Wegener's, GPA) or microscopic polyangiitis (MPA) according to the definitions of the Chapel Hill Consensus Conference (CHCC)
- History of being myeloperoxidase (MPO)-ANCA positive during a disease flare
- In clinical remission with Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) = 0 and off all immunosuppression for ≥ 2 years
- Negative MPO-ANCA and proteinase 3 (PR3)-ANCA by ELISA at screening
Key exclusion criteria (21 listed)
- Use of systemic intravenous (IV) or oral glucocorticoids for ˃ 1 month for any non-vasculitis indication within 8 weeks of the screening visit
- Any prior treatment with rituximab
- Presence of known chronic viral infections or autoimmune diseases
- History of malignancy, excluding non-melanomatous skin cancers or cervical cancer carcinoma in situ within 5 years of the screening visit.
- Use of IV pulse glucocorticoids (methylprednisolone or other) or cyclophosphamide within the year prior to the screening visit
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 |
|---|---|---|
| Venipuncture for blood sample collectionAlso: Peripheral venous blood drawAnalysis samples from the blood sample collection at specific time points. | Procedure or surgery | AAV Discontinuing Immunosuppression, Healthy Controls, Non-Tolerant AAV, Tolerant AAV |
Primary outcome
Tolerance Biomarker Identification
Time frame: Difference from baseline to week 26
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.
3 secondary outcomes
Tolerance Signature Stability
Time frame: Baseline to Week 26
Tolerance Signature Versus Clinical Status
Time frame: Baseline to Week 26
Immunosuppression Associated Signature
Time frame: Baseline to 8 Weeks Post-Immunosuppression Withdrawal
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The National Institute of Allergy and Infectious DiseasesLink provided by the sponsor.
- Immune Tolerance Network (ITN)Link provided by the sponsor.
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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.
Alan Salama, MD study chair
University College London, Centre for Nephrology
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of ANCA-Associated Vasculitis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United Kingdom.
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 27 inclusion and 21 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 20 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. 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 20 May 2016). 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?
Tolerance Biomarker Identification (time frame: Difference from baseline to week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 May 2016.