The Assessment of Prednisone In Remission Trial - Centers of Excellence Approach

Patients with granulomatosis with polyangiitis (GPA, Wegener's) will be recruited at one of
the Vasculitis Centers of Excellence. Participants will be randomized 1:1 either to taper
their prednisone dose down to 5 mg/day according to a standardized schedule and stay at 5
mg/day of prednisone for the duration of the study or until a study endpoint, or taper their
prednisone dose down to 0 mg/day using a standard schedule and stay at 0 mg/day for the
duration of the study or until a study endpoint. All study participants will be followed for
6 months (from reaching a prednisone dose of 5 mg/day) or until an increase of prednisone
dose (after randomization) occurs, whichever comes first.

Participants will have up to four study visits, a screening visit (visit 1), a baseline
(visit 2), a month 3 visit (visit 3) and a month 6 or flare visit (visit 3) and up to two
follow-up phone calls from the study coordinator at randomization and at month 1
(randomization and 1 month phone call may be combined if randomization occurs at month 1).

This study is a project of the Vasculitis Clinical Research Consortium (VCRC) funded through
the National Institutes of Health Rare Diseases Clinical Research Network (RDCRN) with the
purpose of promoting vasculitis research. The VCRC is the major clinical research
infrastructure in North America for the study of vasculitis, and eight VCRC Centers of
Excellence will be recruiting for this study.

Inclusion Criteria:

1. Established diagnosis of granulomatosis with polyangiitis (GPA) where patients will
need to meet at least 2 of the 5 for the classification of GPA, at least one of which
must be criterion d or e:

The modified American College of Rheumatology (ACR) criteria are:

A. Nasal or oral inflammation, defined as the development of painful or painless oral
ulcers or purulent or bloody nasal discharge.

B. Abnormal chest radiograph, defined as the presence of nodules, fixed infiltrates,
or cavities.

C. Active urinary sediment, defined as microscopic hematuria (>5 red blood cells per
high power field) or red blood cell casts.

D. Granulomatosis inflammation on biopsy, defined as histologic changes showing
granulomatous inflammation within the wall of an artery or in the perivascular or
extravascular area. Note: Pauci-immune glomerulonephritis seen on kidney biopsy will
suffice for this criterion.

E. Positive anti-neutrophil cytoplasmic antibody (ANCA) test specific for proteinase-3
measures by enzyme-linked immunoassay.

Patients who are myeloperoxidase (MPO) positive or ANCA negative are still eligible
for this study if they meet the criteria above and are felt to have GPA.

2. Active disease within the prior 12 months (initial presentation or relapse) that at
time of active disease required treatment with prednisone >20 mg/day.

3. Disease remission at time of enrollment.

4. Prednisone dose at time of enrollment of ≥ 5 mg/day and ≤ 20 mg/day.

5. Participant age of 18 years or greater.

6. If the patient is taking an immunosuppressive medication agent other than prednisone
(maintenance agent) then the maintenance agent must be at a stable dose for one month
prior to enrollment with no plans by the treating physician to change the dose (other
than for safety purposes/toxicity) for the duration of the study (through the month 6
visit or early termination). Acceptable maintenance agents include azathioprine,
leflunomide, 6-mercaptopurine, methotrexate, mycophenolate mofetil, mycophenolate
sodium, or rituximab. Patients may be on trimethoprim/sulfamethoxazole (TMP/SMX) for
use as either a maintenance agent or for prophylaxis for infection. TMP/SMX may be
used in combination with other drugs.

6.1 If the patient is regularly taking trimethoprim/sulfamethoxazole at any dose then the
patient is eligible if there no plans by the treating physician to change the dose after
enrollment (other than dose reduction or discontinuation for safety purposes/toxicity) for
the duration of the study.

Exclusion Criteria:

1. Comorbid condition that has moderate likelihood of requiring a course of prednisone
within one year of enrollment (e.g. chronic obstructive pulmonary disease (COPD), asthma,
adrenal insufficiency).