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

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Brief Title

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

Official Title

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

Brief 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.
    

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.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Ability of abatacept to reduce the treatment failure rate

Secondary Outcome

 Duration of glucocorticoid-free periods

Condition

Granulomatosis With Polyangiitis (Wegener's)

Intervention

Abatacept

Study Arms / Comparison Groups

 Blinded abatacept
Description:  Participants will receive blinded abatacept 125 mg administered by subcutaneous injection once a week for at least 12 months. Subjects may be removed from treatment earlier due to a disease relapse, disease worsening, or if they have not achieved remission by treatment month 6.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

66

Start Date

April 2015

Completion Date

September 2023

Primary Completion Date

August 2023

Eligibility Criteria

        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. If applicable, participating sites will defer to their local
             authorities if they require stricter guidelines on the types of allowable
             contraception methods.

          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 or prednisolone> 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 less than or equal to
             20 ml/min

         12. AST or ALT > 3 times above the upper limit of the normal laboratory range

         13. Known current use of illegal drugs

         14. 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

         15. 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

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

         17. A live vaccination fewer than 3 months before enrollment

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

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

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

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

         22. 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.

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

         24. Treatment with rituximab or any other biologic B cell depleting agent within the past
             6 months

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

         26. Treatment with intravenous immunoglobulin given at an immunomodulatory dosage or
             plasma exchange within the past 3 months. Patients can be enrolled if they are
             otherwise eligible and receiving immunoglobulin replacement for hypogammaglobulinemia.

         27. 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)
      

Gender

All

Ages

15 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Carol A Langford, MD, MHS, 1-888-772-8315, [email protected]

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT02108860

Organization ID

ABROGATE 5527

Secondary IDs

2013-005535-24

Responsible Party

Sponsor

Study Sponsor

University of South Florida

Collaborators

 The Cleveland Clinic

Study Sponsor

Carol A Langford, MD, MHS, Principal Investigator, The Cleveland Clinic


Verification Date

December 2020