Defining Immune Tolerance in ANCA-associated Vasculitis (AAV)

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Clinical Trial

— AAV  

Official title:

Defining Immune Tolerance in ANCA-associated Vasculitis (AAV)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01934504
• Other study ID #: DAIT ITN051AI
• Secondary ID: AVATARS
• Status: Terminated
• Phase: N/A
• First received: August 29, 2013
• Last updated: June 4, 2015
• Start date: December 2013
• Est. completion date: February 2015

Study information

• Verified date: June 2015
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical 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.

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markers that define immunological tolerance so that immunotherapy medicines may be correctly changed and safely withdrawn in some people.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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 BVAS/WG = 0 and off all immunosuppression for >/= 2 years

• Negative MPO-ANCA and PR3-ANCA by ELISA at screening

• 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 <\=150mgdailyor

• 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.

Exclusion Criteria:

Tolerant AAV Participants

• Use of systemic 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

• 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.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Vasculitis

Intervention

Procedure:
• Venipuncture for blood sample collection
Analysis samples from the blood sample collection at specific time points.

Locations

Country	Name	City	State
United Kingdom	School of Immunity and Infection, Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham	Birmingham	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Hammersmith Hospital	London	England
United Kingdom	University College London, Centre for Nephrology	London	England

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Immune Tolerance Network (ITN)

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Difference from baseline to week 26	No
Secondary	Tolerance Signature Stability	Measurement of the stability of a tolerance immune signature in patients with AAV over time	Baseline to Week 26	No
Secondary	Tolerance Signature versus Clinical Status	Correlation of possible changes in the tolerance signature with changes in clinical status	Baseline to Week 26	No
Secondary	Immunosuppression Associated Signature	Definition of an immune signature associated with maintenance immunosuppression	Baseline to 8 Weeks Post-Immunosuppression Withdrawal	No

External Links

•   Immune Tolerance Network (ITN)
•   The National Institute of Allergy and Infectious Diseases