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

Information source: University of South Florida
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Granulomatosis With Polyangiitis (Wegener's); Granulomatosis With Polyangiitis; Wegener's Granulomatosis; ANCA-Associated Vasculitis

Intervention: Abatacept (Drug); placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: University of South Florida

Official(s) and/or principal investigator(s):
Carol A Langford, MD, MHS, Principal Investigator, Affiliation: The Cleveland Clinic
Jeffrey P Krischer, PhD, Principal Investigator, Affiliation: University of South Florida
Peter A Merkel, MD, MPH, Principal Investigator, Affiliation: University of Pennsylvania

Overall contact:
Cristina Burroughs, Phone: 813-396-9237, Email: abrogate@epi.usf.edu

Summary

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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Treatment failure after 12 months of study treatment

Secondary outcome:

Duration of glucocorticoid-free periods

Duration of remission with abatacept versus placebo

Severity of relapses in those treated with abatacept versus placebo

Health-related quality of life in those treated with abatacept versus placebo

Number and severity of adverse events

Detailed description: 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.

Eligibility

Minimum age: 15 Years. Maximum age: N/A. Gender(s): Both.

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)

Locations and Contacts

Cristina Burroughs, Phone: 813-396-9237, Email: abrogate@epi.usf.edu

University of British Columbia, St. Paul's Rheumatology Clinic, Vancouver, British Columbia V6Z 1Y6, Canada; Recruiting
Shifana Premji, Phone: 604.806.8871, Email: SPremji@cheos.ubc.ca
Kam Shojania, MD, FRCPC, Principal Investigator
Natasha Dehghan, MD, FRCPC, Sub-Investigator

University of Kansas Medical Center, Kansas City, Kansas 66160, United States; Recruiting
Caitlin McMillian, Phone: 913-588-0681, Email: cmcmillian@kumc.edu
Jason Springer, MD, Principal Investigator

Boston University School of Medicine, Boston, Massachusetts 02118, United States; Recruiting
Naomi Amudala, NP, Phone: 617-414-2512, Email: namudala@bu.edu
Paul Monach, MD, Principal Investigator

Hospital for Special Surgery, New York, New York 10021, United States; Recruiting
Chris Hatzis, Phone: 212-774-7194, Email: hatzisc@hss.edu
Robert F Spiera, MD, Principal Investigator
Lindsay Lally, MD, Sub-Investigator

Cleveland Clinic, Cleveland, Ohio 44195, United States; Recruiting
Carol A Langford, MD, MHS, Phone: 216-445-6056, Email: langfoc@ccf.org
Katie Gartner, Phone: 216-445-1397, Email: gartnek@ccf.org
Carol A Langford, MD, MHS, Principal Investigator

St. Joseph's Hospital, Hamilton, Hamilton, Ontario, Canada; Recruiting
Sandra Messier, Phone: 905-522-1155, Ext: 35873, Email: smessier@stjoes.ca
Nader Khalidi, MD, Principal Investigator

Mount Sinai Hospital, Toronto, Toronto, Ontario M5T 3L9, Canada; Recruiting
Sam Jagadeesh, Phone: 416-586-8616, Email: sjagadeesh@mtsinai.on.ca
Simon Carette, MD, Sub-Investigator
Christian Pagnoux, MD, Principal Investigator

University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States; Recruiting
Matthew MacDonald, Phone: 215-614-4408, Email: mmacdona@upenn.edu
Peter A Merkel, MD, MPH, Principal Investigator

University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States; Recruiting
Carol Oriss, Phone: 412-648-0148, Email: orissca@upmc.edu
Larry Moreland, MD, Principal Investigator

University of Utah, Salt Lake City, Utah 84132, United States; Recruiting
Nereida Ortez, Phone: 801-585-1380, Email: nereida.ortez@hsc.utah.edu
Curry Koening, MD, Principal Investigator

Additional Information

Vasculitis Clinical Research Consortium

Starting date: April 2015
Last updated: July 23, 2015

Page last updated: August 23, 2015

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