An official website of the United States government
          Here’s how you know
        Here’s how you know**Official websites use .gov**A
              **.gov** website belongs to an official government
              organization in the United States.
        **Secure .gov websites use HTTPS**A
              **lock** (
              Locked padlock icon) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.
 Top Utility Nav
        
        
        Asian-Language Resources
        
        Portal en español


Site search Mega Menu
  

        

        Home
                  Health Topics
                                      
    
  Health Topics

    Arthritis and Rheumatic Diseases
          
    Muscle and Bone Diseases
          
    Skin Diseases
          
    All Diseases and Conditions
          
    Publication Catalog
                  Grants & Funding
                                      
    
  Grants & Funding

    Current Funding Opportunities
          
    Supported Scientific Programs
          
    NIAMS-Supported Programs
          
    Applying for a Grant
          
    NIH Policies and Guidance
          
    Peer Review and Grants Administration Resources
          
    Types of Funding Mechanisms (Activity Codes)
                  Labs @ NIAMS
                                      
    
  Labs @ NIAMS

    NIAMS Labs and Core Facilities
          
    Research Faculty
          
    Research Areas
          
    NIAMS Scientific Advances
          
    Training and Career Development
                  Clinical Trials
                                      
    
  Clinical Trials
      
            For Principal Investigators

    Clinical Trial Policies, Guidelines, and Templates
          
    Conducting Clinical Trials
          
    Register with ClinicalTrials.gov

For Patients

What is a Clinical Trial?
	Clinical Trials at NIAMS
	Clinical Trials in the Spotlight
                  News & Events
                                      
    
  Newsroom

    All NIAMS News
          
    NIAMS Newsletters
          
    Meetings & Events
                  About NIAMS
                                      
    
  About NIAMS

    Director's Page
          
    NIAMS Organization
          
    Strategic Plan Fiscal Years 2020-2024
          
    Staff Directory
          
    NIAMS Budget
          
    Partnerships
          
    Contact NIAMS
                  Community Outreach
                                      
    
  Community Outreach

    Bone Health
          
    Joint Health
          
    Muscle, Tendon, and Ligament Health
          
    Skin Health
          
    Health Information For Kids And Young Adults
          
    Health Information For Older Adults/Seniors
          
    Printable Materials for Community Events
          
    Resources in Other Languages
          
    Annual Health Observances
          
    Social Media Resources Breadcrumb
    Home
          Grants & Funding: The NIAMS Extramural Program
          Clinical Trials in the Spotlight
          Abatacept (CTLA4-Ig) for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis (Wegener's) (ABROGATE)








Abatacept (CTLA4-Ig) for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis (Wegener's) (ABROGATE) FacebookEmailPrintFacebookEmail     
    Clinical Trials in the Spotlight Main Page

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports a range of clinical trials studying new and existing interventions for prevention and treatment of arthritis, musculoskeletal, and skin diseases.  Investigators supported by the NIAMS need your help finding individuals to participate in clinical trials.  Participating in clinical trials allows you to play an active role as a volunteer in research and contribute to generating new knowledge about the disease/condition, and potentially future treatments.  The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible.

Study Description

Granulomatosis with polyangiitis (Wegener’s) (GPA) is a systemic inflammatory disease that is characterized by necrotizing, granulomatous inflammation and vasculitis of the small to medium-sized vessels. Despite the availability of medications that can induce remission, disease relapses occur in up to 75% of patients with GPA. The majority of these relapses are not severe, but can nevertheless result in incremental significant morbidity, from both GPA and the use of immunosuppressive treatment required to manage such relapses.   Abatacept (CTLA4-Ig) is comprised of the ligand-binding domain of CTLA4 plus human immunoglobulin. Through this construct abatacept carries the potential to modulate the costimulatory signal required for T cell activation. Based on laboratory data supporting a potential role for activated CD4 T cells in the pathogenesis of GPA, an open-label study was conducted to examine the role of abatacept in non-severe relapsing GPA. In 20 GPA patients treated with abatacept, 90% improved, 80% achieved remission, and 70% reached common closing. Eleven out of 15 patients were able to discontinue prednisone.

This 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. The primary objective of this trial is to determine the efficacy of abatacept to reduce the treatment failure rate. The secondary objectives are to determine the duration of glucocorticoid-free periods, severity of relapses in those treated with abatacept versus placebo, health-related quality of life in those treated with abatacept versus placebo, prevention of disease- or treatment-related damage with abatacept versus placebo, and safety of abatacept in GPA. This trial will be conducted by the Vasculitis Clinical Research Consortium (VCRC) and the European Vasculitis Society (EUVAS) with support by Bristol-Myers Squibb.

**ELIGIBILITY CRITERIA:**

Ages Eligible for Study:           15 Years and older   (Child, Adult, Older Adult)

Sexes Eligible for Study:          All

Accepts Healthy Volunteers:  No

**Inclusion Criteria:**

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:Nasal or oral inflammation, defined as the development of painful or painless oral ulcers or purulent or bloody nasal discharge
	Abnormal chest radiograph, defined as the presence of nodules, fixed infiltrates, or cavities
	Active urinary sediment, defined as microscopic hematuria (>5 red blood cells per high power field) or red blood cell casts
	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)
	Positive anti-neutrophil cytoplasmic antibody (ANCA) test specific for proteinase-3 or myeloperoxidase measured by enzyme-linked immunoassayRelapse of GPA within the 28 days prior to screening where the active disease features meet the following definition of non-severe disease:No disease manifestations that would be scored as a major element in the BVAS/WG
	Absence of any disease feature that poses an immediate threat to either a critical individual organ or the patient's lifeAge 15 and older
	Willing and able to comply with treatment and follow-up procedures
	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.
	Willing and able to provide written informed consent (and written assent of minor participants if applicable.)

**Exclusion Criteria:**

Presence of involvement that does not meet the criteria for non-severe disease
	Treatment with CYC within 3 months prior to screening
	Treatment with methylprednisolone 1000 mg within 28 days prior to enrollment
	Treatment with prednisone > 30 mg/day for > 28 days immediately prior to study entry
	Initiation or dose increase of the maintenance immunosuppressive agent (MTX, AZA, MA) within 3 months prior to screening
	Evidence of active infection (includes chronic infection)
	Patients who are pregnant or who are nursing
	Known infection with human immunodeficiency virus (HIV), hepatitis C, or a positive hepatitis B surface antigen
	Inability to comply with study guidelines
	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
	Chronic renal insufficiency defined by a creatinine clearance of < or = to 20 ml/min
	Known current use of illegal drugs
	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
	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
	Receipt of an investigational agent or device within 30 days prior to enrollment or 5 half lives of the investigational drug (whichever is longer)
	A live vaccination fewer than 3 months before enrollment
	Current clinical, radiographic, or laboratory evidence of active tuberculosis
	A history of active tuberculosis within the past 3 years even if treated
	A history of active tuberculosis greater than 3 years ago unless there is documentation of prior anti-tuberculosis treatment of appropriate duration and type
	Latent tuberculosis unless there is documentation of prior anti-tuberculosis treatment of appropriate duration and type
	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.
	History of herpes zoster that resolved less than 2 months prior to enrollment
	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
	Treatment with alemtuzumab or anti-thymocyte globulin within the last 12 months
	Treatment with intravenous immunoglobulin or plasma exchange within the past 3 months
	**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)****Study Design:**

Allocation: Randomized

Intervention Model: Parallel Assignment

Masking:Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose: Treatment

**Study Location(s):**

Cedars Sinai Medical Center, Los Angeles, Los Angeles, California, United States, 90048

University of California, San Francisco, San Francisco, California, United States, 94143

University of South Florida Rheumatology, Tampa, Florida, United States, 33612

University of Kansas Medical Center, Kansas City, Kansas, United States, 66160

Boston University School of Medicine, Boston, Massachusetts, United States, 02118

University of Michigan, Ann Arbor, Michigan, United States, 48109

Mayo Clinic Rochester, Rochester, Minnesota, United States, 55902

Hospital for Special Surgery, New York, New York, United States, 10021

Cleveland Clinic, Cleveland, Ohio, United States, 44195

Oregon Health & Science University, Portland, Oregon, United States, 97239

University of Pennsylvania, Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 15261

Vanderbilt University, Nashville, Tennessee, United States, 37240

University of Utah, Salt Lake City, Utah, United States, 84132

University of Calgary, Calgary, Alberta, Canada, T3M 1M4

Alberta Health Services- Edmonton, Edmonton, Alberta, Canada, T6G 2C8

University of British Columbia, St. Paul's Rheumatology Clinic, Vancouver, British Columbia, Canada, V6Z 1Y6

St. Joseph's Hospital, Hamilton, Ontario, Canada

The Ottawa Hospital, Ottawa, Ontario, Canada, k1H 8L6

Mount Sinai Hospital, Toronto, Toronto, Ontario, Canada, M5T 3L9

St. Vincent's University Hospital, Dublin, Ireland

University of Aberdeen, Aberdeen, United Kingdom, AB25 2ZD

University of Cambridge- Addenbrookes Hospital, Cambridge, United Kingdom

**Study Website:**

https://clinicaltrials.gov/ct2/show/NCT02108860?term=NCT02108860&rank=1


Last Updated: August 2019


Back to Top
 About NIAMS
                    Clinical Trials
                    Grants & Funding
                    Health Topics
                    Labs @ NIAMS
              News Room
                    NIAMS Multimedia Library
                    Disclaimer
                    FOIA
                    Contact us
              Privacy Statement
                    Accessibility
                    HHS Vulnerability Disclosure
                    Social Media Moderation Policy
                    NIAMS Archives
        Subscribe to Our E-Newsletters
            Click the button to see different options to sign up for newsletters.
            Click Here to Subscribe
          Follow us on
  
  About NIH
                  Accessibility Support
            FOIA requests
                  No FEAR Act data
            Office of the Inspector General
                  Performance reports
            Privacy Policy