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

  • STATUS
    Recruiting
  • End date
    Sep 28, 2023
  • participants needed
    66
  • sponsor
    University of South Florida
Updated on 28 April 2021
remission
cavities
norplant
chest radiograph
churg-strauss syndrome
anca
granulomatous inflammation
nasal discharge
urinary sediment
anti-neutrophil cytoplasmic antibody
eosinophilic granulomatosis

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.

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.

Details
Condition Autoimmune disease, Wegener's Granulomatosis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Granulomatosis With Polyangiitis, anca-associated vasculitides, anca associated vasculitis
Treatment Placebo, Abatacept
Clinical Study IdentifierNCT02108860
SponsorUniversity of South Florida
Last Modified on28 April 2021

Eligibility

Yes No Not Sure

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 immunoassay
Relapse 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 life
Age 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. If applicable, participating sites will defer to their local authorities if they require stricter guidelines on the types of allowable contraception methods
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 or prednisolone> 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 less than or equal to 20 ml/min
AST or ALT > 3 times above the upper limit of the normal laboratory range
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
Treatment with alemtuzumab or anti-thymocyte globulin within the last 12 months
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
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)
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note