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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 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 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.


Sponsor: University of South Florida

Current Primary Outcome: Treatment failure after 12 months of study treatment [ Time Frame: 12 months ]

Treatment failure will be defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) = 0 or 1 by 6 months.

Relapse will be defined as any of the following after remission: an increase in BVAS/WG, development of a new BVAS/WG item, or symptoms/signs of GPA that cannot be attributed to any cause other than GPA and that requires institution or dosage increase of prednisone.

Disease worsening will be defined as any of the following prior to remission: an increase in BVAS/WG, development of a new BVAS/WG item, or symptoms/signs of GPA that cannot be attributed to any cause other than GPA and that requires institution or dosage increase of prednisone.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Duration of glucocorticoid-free periods [ Time Frame: 12 months ]
    Effect of abatacept on increasing duration of glucocorticoid-free periods for participants. Patients will be treated with abatacept for a minium of 12 months unless they reach study criteria for early termination or until common closing. Common closing will be 12 months after randomization of the final patient.
  • Duration of remission with abatacept versus placebo [ Time Frame: 12 months ]
    Duration of GPA disease remission on participants on abatacept versus placebo. Patients will be treated with abatacept for a minium of 12 months unless they reach study criteria for early termination or until common closing. Common closing will be 12 months after randomization of the final patient.
  • Severity of relapses in those treated with abatacept versus placebo [ Time Frame: 12 months ]
    Severity of GPA disease relapses in those treated with abatacept versus placebo. Patients will be treated with abatacept for a minium of 12 months unless they reach study criteria for early termination or until common closing. Common closing will be 12 months after randomization of the final patient.
  • Health-related quality of life in those treated with abatacept versus placebo [ Time Frame: 12 months ]
    Health-related quality of life in those treated with abatacept versus placebo as assessed using the SF-36 and PROMIS questionnaires. Patients will be treated with abatacept for a minium of 12 months unless they reach study criteria for early termination or until common closing. Common closing will be 12 months after randomization of the final patient.
  • Number and severity of adverse events [ Time Frame: 12 months ]
    Safety of abatacept in patients with GPA as assessed by reported adverse events. Patients will be treated with abatacept for a minium of 12 months unless they reach study criteria for early termination or until common closing. Common closing will be 12 months after randomization of the final patient.


Original Secondary Outcome: Same as current

Information By: University of South Florida

Dates:
Date Received: March 27, 2014
Date Started: April 2015
Date Completion: September 2019
Last Updated: May 1, 2017
Last Verified: May 2017