ABROGATE
Research type
Research Study
Full title
Abatacept (CTLA4-Ig) for the treatment of relapsing, non-severe, granulomatosis with polyangiitis (Wegener's)
IRAS ID
174707
Contact name
David Jayne
Contact email
Sponsor organisation
Univeristy of South Florida
Eudract number
2013-005535-24
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 8 months, 28 days
Research summary
Granulomatosis with polyangiitis (GPA; Wegener’s) is a systemic inflammatory disease affecting the small and medium blood vessels. Up to 75% of patients have relapses which, whilst not always severe, can cause significant morbidity either due to the disease itself or the medications controlling symptoms.
Laboratory data has indicated a potential role for activated CD4 T cells in the progression of GPA. Abatacept is a biological agent which interferes with the action of activated CD4 T cells. A study investigating the role of Abatacept in non-severe relapsing GPA showed that in 20 treated patients, 90% improved, 80% achieved remission, and 70% reached the planned end of treatment phase without relapse. Eleven out of 15 patients were able to stop taking oral steroid (prednisone). Abatacept was found to be well tolerated in this trial, providing encouraging preliminary evidence of a therapeutic use in GPA.
The ABROGATE study is a multicentre, randomised, double-blind placebo-controlled phase III trial, aiming to determine the efficacy of abatacept to reduce treatment failure rate in patients with relapsing non-severe GPA over 12 months. Patients will be randomised to receive weekly subcutaneous injections of either abatacept 125mg or placebo. All patients will receive prednisone 30mg per day which will be tapered according to standardized schedule. Existing maintenance immunosuppressive use at the time of enrolment will not be changed during the study period.
Safety and efficacy data will be collected at months 1, 3, 6, 9 and 12. Patients experiencing a non-severe relapse, non-severe disease worsening or are not in remission by month 6 will be eligible to enter an open-label (non-blinded active treatment) extension period. Patients who experience severe disease relapse or severe worsening of disease will be terminated early, and trial medication stopped. Patients will have a final safety visit 3 months after stopping active treatment.REC name
East of England - Cambridge South Research Ethics Committee
REC reference
16/EE/0028
Date of REC Opinion
12 Apr 2016
REC opinion
Further Information Favourable Opinion