Defining Immune Tolerance in ANCA-associated Vasculitis (AAV)

NCT ID: NCT01934504

Last Updated: 2016-05-20

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 33 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2015-02-28

Brief 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.

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markers that define immunological tolerance so that immunotherapy medicines may be correctly changed and safely withdrawn in some people.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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Tolerant AAV

Tolerant participants with AAV

Venipuncture for blood sample collection

Intervention Type: PROCEDURE

Analysis samples from the blood sample collection at specific time points.

Non-Tolerant AAV

Non-Tolerant participants with ANCA-associated vasculitis (AAV)

Venipuncture for blood sample collection

Intervention Type: PROCEDURE

Analysis samples from the blood sample collection at specific time points.

Healthy Controls

Healthy participants that fulfill eligibility criteria -similar in age to Tolerant and Non-Tolerant AAV participants.

Venipuncture for blood sample collection

Intervention Type: PROCEDURE

Analysis samples from the blood sample collection at specific time points.

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.

Venipuncture for blood sample collection

Intervention Type: PROCEDURE

Analysis samples from the blood sample collection at specific time points.

Interventions

Venipuncture for blood sample collection

Analysis samples from the blood sample collection at specific time points.

Intervention Type: PROCEDURE

Other Intervention Names

Peripheral venous blood draw

Eligibility Criteria

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 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
• 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.

Exclusion Criteria

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:

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Immune Tolerance Network (ITN)

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alan Salama, MD

Role: STUDY_CHAIR

University College London, Centre for Nephrology

Locations

Addenbrooke's Hospital

Cambridge, England, United Kingdom

University College London, Centre for Nephrology

London, England, United Kingdom

Hammersmith Hospital

London, England, United Kingdom

Countries

United Kingdom

Related Links

http://www.niaid.nih.gov/

The National Institute of Allergy and Infectious Diseases

http://www.immunetolerance.org

Immune Tolerance Network (ITN)

Other Identifiers

AVATARS

Identifier Type: OTHER

Identifier Source: secondary_id

DAIT ITN051AI

Identifier Type: -

Identifier Source: org_study_id