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



Status:Recruiting
Conditions:Cardiology
Therapuetic Areas:Cardiology / Vascular Diseases
Healthy:No
Age Range:15 - Any
Updated:10/17/2018
Start Date:April 2015
End Date:September 2022
Contact:Cristina Burroughs
Email:abrogate@epi.usf.edu
Phone:1-888-772-8315

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Abatacept (CTLA4-Ig) for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis (Wegener's) (ABROGATE)

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.

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 GPA. Patients who enter the trial will be maintained on a stable dose of their
maintenance immunosuppressive agent which may include methotrexate (MTX), azathioprine (AZA),
or mycophenolate (MA) and will undergo a blinded randomization to receive abatacept or
placebo. Patients will additionally receive prednisone 30 mg daily that will then be tapered
to zero using a standardized tapering schedule.

If an enrolled patient experiences a non-severe relapse or non-severe disease worsening
though common closing, or if they have not achieved remission by month 6, they will have the
option of entering an open-label trial period whereby they would receive abatacept in
conjunction with their maintenance immunosuppressive and a standardized glucocorticoid taper.
Patients with a severe disease relapse or severe disease worsening will have met criteria for
early termination criteria and be removed from active study treatment. Patients will remain
on study until reaching criteria for early termination or until common closing, 12 months
after randomization of the final patient. After common closing or early termination, patients
will be treated with best medical judgment and will undergo a post-treatment safety visit 3
months after coming off of study treatment.

Inclusion Criteria:

1. Patients must be considered as being best characterized as GPA and not microscopic
polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) and 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 or myeloperoxidase 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. Women should continue the use of an effective
means of birth control for a minimum of 14 weeks after the last dose of study drug.
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 (and written assent of minor
participants if applicable.)

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)
We found this trial at
15
sites
9500 Euclid Avenue
Cleveland, Ohio 44106
216.444.2200
Principal Investigator: Carol A Langford, MD, MHS
Phone: 216-445-6056
Cleveland Clinic Cleveland Clinic is committed to principles as presented in the United Nations Global...
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72 East Concord Street
Boston, Massachusetts 02118
(617) 638-5300
Principal Investigator: Paul Monach, MD
Phone: 617-414-2512
Boston University School of Medicine A leader in medical education and research, Boston University School...
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4200 Fifth Ave
Pittsburgh, Pennsylvania 15260
(412) 624-4141
Principal Investigator: Larry Moreland, MD
Phone: 412-647-2638
University of Pittsburgh The University of Pittsburgh is a state-related research university, founded as the...
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Principal Investigator: Cailin Sibley, MD, MHS
Phone: 503-494-6115
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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201 Presidents Circle
Salt Lake City, Utah 84108
801) 581-7200
Principal Investigator: Curry Koening, MD
Phone: 801-585-0797
University of Utah Research is a major component in the life of the U benefiting...
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500 S State St
Ann Arbor, Michigan 48109
(734) 764-1817
Principal Investigator: Ora Gewurz-Singer, MD
Phone: 734-936-4009
University of Michigan The University of Michigan was founded in 1817 as one of the...
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Calgary, Alberta
Principal Investigator: Aurore Fifi-Mah, MD
Phone: 403-210-7113
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3901 Rainbow Blvd
Kansas City, Kansas 66160
(913) 588-5000
Principal Investigator: Jason Springer, MD
Phone: 913-588-0681
University of Kansas Medical Center The University of Kansas Medical Center serves Kansas through excellence...
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Los Angeles, California 90048
Phone: 310-423-3032
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2201 West End Ave
Nashville, Tennessee 37232
(615) 322-7311
Principal Investigator: Narender Annapureddy, MD
Phone: 615-875-8356
Vanderbilt University Vanderbilt offers undergraduate programs in the liberal arts and sciences, engineering, music, education...
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535 E 70th St
New York, New York 10021
(212) 606-1000
Principal Investigator: Robert F Spiera, MD
Phone: 212-774-2123
Hospital for Special Surgery Founded in 1863, Hospital for Special Surgery is the nation
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3451 Walnut St
Philadelphia, Pennsylvania 19104
1 (215) 898-5000
Principal Investigator: Peter A Merkel, MD, MPH
Phone: 215-614-4407
Univ of Pennsylvania Penn has a long and proud tradition of intellectual rigor and pursuit...
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200 First Street SW
Rochester, Minnesota 55905
507-284-2511
Principal Investigator: Ulrich Specks, MD
Phone: 800-743-1606
Mayo Clinic Rochester Mayo Clinic is a nonprofit worldwide leader in medical care, research and...
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San Francisco, California 94143
Principal Investigator: Sarah Goglin, MD
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12901 Bruce B Downs Boulevard
Tampa, Florida 33612
Principal Investigator: Yih Chang Lin, MD
Phone: 813-974-2473
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