Clinical Trial: A Study to Investigate Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Double-blind, Randomised, Placebo-controlled Study to Investigate the Efficacy and Safety of Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis

Brief Summary: The purpose of this randomized, double-blind study is to investigate the efficacy and safety of mepolizumab (300 milligram [mg] administered subcutaneously [SC] every 4 weeks) compared with placebo over a 52-week study treatment period in subjects with relapsing or refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA) receiving standard of care therapy including background corticosteroid therapy with or without immunosuppressive therapy. During the treatment period, in accordance with standard of care, corticosteroid dose will be tapered. The key outcomes in the study focus on evaluation of clinical remission, defined as Birmingham Vasculitis Activity Score (BVAS)=0 with a corticosteroid dose of <=4 mg/day prednisolone/prednisone, reduction in disease relapse and reduction in corticosteroid requirement.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

• Total accrued duration of remission [ Time Frame: From Baseline to Week 52 ]
  The accrued number of weeks where BVAS=0 plus prednisolone/prednisone dose <=4 mg/day over the 52 week study treatment period reported as proportion of subjects achieving remission in the following categories: Zero, >0 to <12 weeks, 12 to <24 weeks, 24 to <36 weeks, >=36 weeks
• The proportion of subjects who are in remission at both Weeks 36 and 48 of the study treatment period [ Time Frame: Weeks 36 and 48 ]
  Remission is defined as BVAS=0 and prednisolone/prednisone dose <=4 mg/day

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Time to first confirmed EGPA relapse [ Time Frame: Baseline to Week 52 ]
  EGPA relapse is defined as worsening or persistence of active disease characterised by active vasculitis (BVAS >0) or active asthma symptoms and/or signs with a corresponding worsening in Asthma Control Questionnaire (ACQ) 6 score or active nasal and/or sinus disease with a corresponding worsening in at least one of the sino-nasal symptom questions warranting an increased dose of OCS therapy or an increased dose or addition of immunosuppressive therapy or hospitalisation related to EGPA worsening
• The proportion of subjects with an average daily prednisolone/prednisone dose of 0 mg, >0 to <=4.0 mg, >4.0 to <=7.5 mg and >7.5 mg during the last 4 weeks of the study treatment period (48 through 52) [ Time Frame: Week 48 to Week 52 ]
• The proportion of subjects in each treatment group who achieve remission (BVAS=0 and prednisolone/prednisone dose <=4 mg/day) within the first 24 weeks of the study and then remain in remission for the remainder of the study treatment period [ Time Frame: Baseline to Week 52 ]
• Total accrued duration of remission, i.e., the accrued number of weeks where BVAS=0 plus prednisolone/prednisone dose ≤7.5 mg/day over the 52 week study treatment period [ Time Frame: Baseline to Week 52 ]
• The proportion of subjects who are in remission (defined as BVAS=0 plus prednisolone/prednisone dose ≤7.5 mg/day) at both Weeks 36 and 48 of the study treatment period. [ Time Frame: Baseline to Week 52 ]
• The proportion of subjects who achieve remission (BVAS=0 and prednisolone/prednisone ≤7.5 mg/day) within the first 24 weeks and remain in remission for the remainder of the study treatment period. [ Time Frame: Baseline to Week 52 ]

Original Secondary Outcome:

• Time to first confirmed EGPA relapse [ Time Frame: Baseline to Week 52 ]
  EGPA relapse is defined as worsening or persistence of active disease characterised by active vasculitis (BVAS >0) or active asthma symptoms and/or signs with a corresponding worsening in Asthma Control Questionnaire (ACQ) 6 score or active nasal and/or sinus disease with a corresponding worsening in at least one of the sino-nasal symptom questions warranting an increased dose of OCS therapy or an increased dose or addition of immunosuppressive therapy or hospitalisation related to EGPA worsening
• The proportion of subjects with an average daily prednisolone/prednisone dose of 0 mg, >0 to <=4.0 mg, >4.0 to <=7.5 mg and >7.5 mg during the last 4 weeks of the study treatment period (48 through 52) [ Time Frame: Week 48 to Week 52 ]
• The proportion of subjects in each treatment group who achieve remission (BVAS=0 and prednisolone/prednisone dose <=4 mg/day) within the first 24 weeks of the study and then remain in remission for the remainder of the study treatment period [ Time Frame: Baseline to Week 52 ]

Dates:
Date Received: December 19, 2013
Date Started: February 2014
Date Completion:
Last Updated: March 13, 2017
Last Verified: March 2017