Accepted for/Published in: JMIR Research Protocols
Date Submitted: Oct 12, 2019
Date Accepted: Feb 3, 2020
Date Submitted to PubMed: Feb 23, 2020
A randomized, double-blind, active-controlled, Phase 3 study to evaluate the safety and efficacy of avacopan, a C5a receptor inhibitor, in patients with ANCA-associated vasculitis treated concomitantly with rituximab or cyclophosphamide/ azathioprine
ABSTRACT
Background:
Anti-neutrophil cytoplasmic antibody-associated vasculitis (ANCA-associated vasculitis) is a serious, often life-threatening disease. In new-onset disease or relapses, the standard treatment is immunosuppressive therapy with glucocorticoids; these therapies are associated with substantial short- and long-term toxicity. Complement component 5a (C5a) binding to C5a receptor (C5aR) may play a central role in the pathogenesis of ANCA-associated vasculitis. Avacopan is a novel, orally bioavailable, and highly selective antagonist of human C5aR. Avacopan does not interfere with the production of C5b or the membrane attack complex (i.e., terminal complement complex), and does not block C5a binding to a second receptor, C5L2 (also called C5aR2), shown to be protective in anti-MPO glomerulonephritis. This trial will evaluate if avacopan replaces the need for chronic glucocorticoids in the treatment of ANCA-associated vasculitis.
Objective:
To determine the proportions of patients in remission at week 26 and with sustained remission at week 52, defined as Birmingham Vasculitis Activity Score = 0 and not taking glucocorticoids within the 4 weeks prior to week 26 and 52, respectively.
Methods:
The “Avacopan Development in Vasculitis to Obtain Corticosteroid elimination And Therapeutic Efficacy study (ADVOCATE)” is a randomized, double-blind, active-comparator (prednisone), 2-arm study evaluating the safety and efficacy of avacopan versus prednisone, administered in combination with other immunosuppressive therapy. Eligible subjects will have active disease requiring induction of remission. Subjects are stratified based on type of immunosuppressive therapy, ANCA subtype, and new or relapsing disease. Target sample size is 300 patients, enrolled at over 200 sites globally. All authors and local ethics committees approved the study design. All patients will provide informed consent.
Results:
Patient enrollment was completed in Q4 2018. Topline results are anticipated by Q1 2020.
Conclusions:
Results will be released irrespective of whether the findings are positive or negative. Clinical Trial: ClinicalTrials.gov NCT02994927
Citation
Request queued. Please wait while the file is being generated. It may take some time.
Copyright
© The authors. All rights reserved. This is a privileged document currently under peer-review/community review (or an accepted/rejected manuscript). Authors have provided JMIR Publications with an exclusive license to publish this preprint on it's website for review and ahead-of-print citation purposes only. While the final peer-reviewed paper may be licensed under a cc-by license on publication, at this stage authors and publisher expressively prohibit redistribution of this draft paper other than for review purposes.