Abatacept in Treating Adults With Mild Relapsing Wegener’s Granulomatosis

Brief Title

Abatacept in Treating Adults With Mild Relapsing Wegener's Granulomatosis

Official Title

A Multi-Center, Open-label Pilot Study of Abatacept (CTLA4-Ig) in the Treatment of Mild Relapsing Wegener's Granulomatosis

Brief Summary

      Wegener's granulomatosis (WG) is a rare disease that causes inflammation of blood vessels, or
      vasculitis. It may involve many different parts of the body, but typically affects the upper
      and lower respiratory tract and kidneys. The purpose of this study is to determine the safety
      and effectiveness of the medication abatacept in treating adults with mild relapsing WG.
    

Detailed Description

      Current standard treatment for WG involves various medications and is based on disease
      severity. Unfortunately, more than 50% of people experience a relapse after remission,
      placing them at risk for additional organ damage and medication toxicity. To prevent this,
      safer and more effective treatments for mild relapses are needed. Several studies have shown
      that activated T cells, a type of white blood cell important in regulating immune responses,
      play a role in WG. Abatacept, an immunoglobulin-based medication approved by the FDA to treat
      rheumatoid arthritis, acts by preventing T-cell activation and may be useful in treating mild
      relapses of WG. The purpose of this study is to determine the safety and effectiveness of
      abatacept in treating adults with mild relapsing WG.

      Participants will receive abatacept intravenously at study visits on Days 1, 15, and 29, and
      then once a month thereafter. A participant's abatacept dose is based on body weight and will
      remain the same throughout the study. Participants who are receiving maintenance
      immunosuppressive medications consisting of methotrexate, azathioprine, or mycophenolate
      mofetil at the time of enrollment will remain on these medications without dosage increase or
      reduction. Eligible participants may be on up to prednisone 15mg daily at the time of
      relapse. Following the development of relapse, participants may be treated with up to
      prednisone 30mg daily if necessary, but must to be back to the same dose that they had been
      on prior to relapse by Month 2. All study visits include medication review, physical exam,
      blood and urine collection, and questionnaires. A chest x-ray, computed tomography (CT) scan
      of the chest and sinuses, and lung function testing will occur at some study visits.
      Participants whose symptoms did not improved by Month 2 will be taken off abatacept. Any
      participants undergoing early termination or, after common closing, will undergo three
      follow-up study visits at 1, 3, and 6 months after the end of treatment.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Safety of Abatacept - Number of Participants With Adverse Events

Secondary Outcome

 Disease Remission

Condition

Wegener's Granulomatosis

Intervention

Abatacept

Study Arms / Comparison Groups

 1

Description:  Participants will receive abatacept intravenously at study visits on Days 1, 15, and 29, and then once a month thereafter.

Publications

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

Recruitment Status

Drug

Estimated Enrollment

20

Start Date

February 2008

Completion Date

August 2011

Primary Completion Date

August 2011

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of WG, meeting at least 2 of the 5 modified American College of Rheumatology
             (ACR) criteria. More information about this criterion can be found in the protocol.

          -  Relapse of WG within the past 28 days where disease activity is confined to one or
             more of the following sites and where the symptoms/signs are of such a nature that the
             usual treatment would consist of the reinstitution or increase in GC to no more than
             prednisone 30mg daily and/or an increase or addition of a second immunosuppressive
             agent other than CYC (more specific information about this criterion can be found in
             the protocol):

               1. Sinonasal disease

               2. Oral mucosa ulceration

               3. Skin disease

               4. Musculoskeletal disease

               5. Pulmonary parenchymal disease

               6. Mild ocular disease

               7. Subglottic inflammation without significant stenosis

               8. Otic disease

               9. Breast involvement

              10. Urogenital involvement

              11. Other mild disease

          -  Age of 15 years or older

          -  Willing and able to undergo treatment and attend follow-up visits

          -  Willing to use effective forms of contraception throughout the study

        Exclusion Criteria:

          -  Disease involvement that does not meet the criteria for mild disease. More information
             about this criterion can be found in the protocol.

          -  Disease activity that would usually be treated first with cyclophosphamide

          -  Presence of disease activity for which the investigator would normally treat the
             participant with more than prednisone 30 mg daily.

          -  Receiving cyclophosphamide at study entry

          -  Treatment with prednisone at a dose of more than 15 mg daily at the time of relapse.
             Subjects will be eligible if prednisone was initiated or dose increased in the period
             between relapse and study enrollment provided that the prednisone dose was 15 mg daily
             or less at the time when the relapse occurred, the prednisone dosage was increased no
             higher than 30 mg daily following the recognition of relapse, and that the dosage
             increase was made no more than 28 days prior to enrollment.

          -  Active infection

          -  HIV infected, hepatitis C virus infected, or positive for hepatitis B

          -  Unable to follow through with study participation

          -  Cytopenia, defined as platelet count less than 80,000/mm3, absolute neutrophil count
             less than 1500/mm3, OR hematocrit less than 20%

          -  Kidney insufficiency

          -  Use of illegal drugs

          -  Any other uncontrolled disease that would prevent participation

          -  History of cancer. More information about this criterion can be found in the protocol.

          -  Received an investigational medication or procedure within 30 days of study entry

          -  Received a live vaccine within 4 weeks of study entry

          -  Positive tuberculin skin test. More information about this criterion can be found in
             the protocol.

          -  Tuberculosis as indicated by radiographic evidence

          -  Past treatment with rituximab within the past 12 months, or past treatment with
             rituximab more than 12 months ago where the B lymphocyte count has not returned to
             normal

          -  Certain other diseases. More information about this criterion can be found in the
             protocol.

          -  Pregnant or breastfeeding
      

Gender

All

Ages

15 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Carol A. Langford, MD, MHS, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00468208

Organization ID

RDCRN 5522

Secondary IDs

U54AR057319

Responsible Party

Sponsor

Study Sponsor

University of Pennsylvania

Collaborators

 Office of Rare Diseases (ORD)

Study Sponsor

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

Verification Date

December 2015