Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis (Wegener's)

Multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of
abatacept to achieve sustained glucocorticoid-free remission in patients with relapsing
non-severe granulomatosis with polyangiitis (Wegener's) (GPA) . Participants will be
randomized 1:1 to receive either abatacept 125 mg or placebo administered by subcutaneous
injection once a week. Participants will continue on study treatment for a minimum of 12
months unless they experience a disease relapse or disease flare.

Participants who experience a non-severe disease relapse, non-severe disease worsening, or
who have not achieved remission by month 6 will have the option of entering an open-label
trial period whereby they would receive open-label abatacept.

Eligibility Criteria

Inclusion Criteria:

1. Patients must have met at least 2 of the 5 modified ACR classification criteria for
GPA. These do not need to be present at the time of study entry. The modified ACR
criteria are:

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

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

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

4. Granulomatous inflammation on biopsy, defined as histologic changes showing
granulomatous inflammation within the wall of an artery or in the perivascular
or extravascular area (artery or arteriole)

5. Positive anti-neutrophil cytoplasmic antibody (ANCA) test specific for
proteinase-3, measured by enzyme-linked immunoassay

2. Relapse of GPA within the 28 days prior to screening where the active disease
features meet the following definition of non-severe disease:

1. No disease manifestations that would be scored as a major element in the BVAS/WG

2. Absence of any disease feature that poses an immediate threat to either a
critical individual organ or the patient's life

3. Age 15 and older

4. Willing and able to comply with treatment and follow-up procedures

5. Both women and men must be willing to use an effective means of birth control while
receiving treatment through this study. Effective contraception methods include
abstinence, oral contraceptives (birth control pills), IUD, diaphragm, Norplant,
approved hormone injections, condoms, or medical sterilization.

6. Willing and able to provide written informed consent with the written assent of those
< 18 years of age

Exclusion Criteria:

1. Presence of involvement that does not meet the criteria for non-severe disease

2. Treatment with CYC within 3 months prior to screening

3. Treatment with methylprednisolone 1000 mg within 28 days prior to enrollment

4. Treatment with prednisone > 30 mg/day for > 28 days immediately prior to study entry

5. Initiation or dose increase of the maintenance immunosuppressive agent (MTX, AZA, MA)
within 3 months prior to screening

6. Evidence of active infection (includes chronic infection)

7. Patients who are pregnant or who are nursing

8. Known infection with human immunodeficiency virus (HIV), hepatitis C, or a positive
hepatitis B surface antigen

9. Inability to comply with study guidelines

10. Cytopenia: platelet count < 100,000/mm3, white blood cell count (WBC) < 3,000/mm3 (3
x 109/L), absolute neutrophil count < 1500/mm3, hemoglobin (Hgb) < 8.5 g/dL

11. Chronic renal insufficiency defined by a creatinine clearance of < or = to 20 ml/min

12. Known current use of illegal drugs

13. Other uncontrolled disease (co-morbidity) that could prevent a patient from
fulfilling the study requirements or that would substantially increase the risk of
study procedures

14. History of malignancy within the past five years or any evidence of persistent
malignancy, except fully excised basal cell or squamous cell carcinomas of the skin,
or cervical carcinoma in situ which has been treated or excised in a curative
procedure

15. Receipt of an investigational agent or device within 30 days prior to enrollment or 5
half lives of the investigational drug (whichever is longer)

16. A live vaccination fewer than 3 months before enrollment

17. Current clinical, radiographic, or laboratory evidence of active tuberculosis

18. A history of active tuberculosis within the past 3 years even if treated

19. A history of active tuberculosis greater than 3 years ago unless there is
documentation of prior anti-tuberculosis treatment of appropriate duration and type

20. Latent tuberculosis unless there is documentation of prior anti-tuberculosis
treatment of appropriate duration and type

21. Latent tuberculosis currently being treated with isoniazid (INH) or other therapy for
latent tuberculosis given according to local health authority guidelines (e.g.,
Center for Disease Control (CDC)) who have received such therapy for 4 weeks or less
prior to randomization (Day 1). Subjects with a positive tuberculosis screening test
indicative of latent tuberculosis will be eligible for the study if they have no
evidence of current tuberculosis on chest xray at screening and they are actively
being treated for tuberculosis with INH or other therapy for latent tuberculosis
given according to local health authority guidelines (e.g., CDC) that has been given
for at least 4 weeks prior to randomization (Day 1). These subjects must complete
treatment according to local health authority guidelines.

22. History of herpes zoster that resolved less than 2 months prior to enrollment

23. Treatment with rituximab or any other biologic B cell depleting agent within the past
6 months or past treatment with rituximab or any other biologic B cell depleting
agent where the B lymphocyte count remains < 60 cells/uL

24. Treatment with alemtuzumab or anti-thymocyte globulin within the last 12 months

25. Treatment with intravenous immunoglobulin or plasma exchange within the past 3 months

26. Treatment with infliximab, etanercept, adalimumab, tocilizumab, or any other biologic
agent within the past 3 months or 5 half lives of the agent (whichever is longer)

Principal Investigator

Jason Springer, MD

Study Contact

Caitlin McMillian, cmcmillian@kumc.edu, 913-588-0681

Estimated Completion Date

Wednesday, August 1, 2018

ClinicalTrials.gov #

NCT02108860
07/23/2015