Abstract: INFO27
ADVOCATE: A randomized phase 3 trial evaluating the safety and efficacy of avacopan in patients with new diagnosed or relapsing anti-neutrophil cytoplasmic antibody-associated vasculitis (NCT02994927)
Session Information
- Informational Posters
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category:
- No subcategory defined
Author
- Jayne, David R.W., University of Cambridge, Cambridge, United Kingdom
Group or Team Name
- On behalf of Chemocentryx
Description
Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a potentially life-threatening systemic autoimmune disease characterized by relapses and remissions. Treatment is usually initiated with high-dose glucocorticoids (hdGCS) in combination with rituximab (RTX) or cyclophosphamide (CYC) to induce remission followed by less intensive treatment to prevent relapse. Overall burden of disease remains high, with progressive organ system damage and morbidity attributable to therapy. hdGCS are associated with increased infection risk, metabolic syndrome, bone loss, and an overall negative impact on quality of life (QOL). There is a need for less toxic treatment alternatives for AAV. Avacopan (previously CCX168) is a novel, orally bioavailable, highly selective antagonist of human C5a receptor that has demonstrated promising efficacy and a favorable safety profile when administered for 12 weeks in Phase 2 studies of patients with active AAV (NCT0136388, NCT02222155).
The ongoing ADVOCATE trial is a double-blind, parallel-arm, active-comparator randomized trial comparing avacopan vs hdGCS in patients (age ≥ 12 yrs) with AAV, when co-administered with either 1) RTX OR 2) CYC followed by azathioprine or mycophenolate mofetil, for ≤ 1 yr. The choice of RTX vs CYC is based on investigator judgement. Patients are stratified by: a) intended use of RTX vs CYC, b) ANCA type (PR3-ANCA vs MPO-ANCA), and c) newly diagnosed vs relapsing disease.
The primary endpoints are 1) proportion of patients in remission at week 26 based on BVAS=0 and not taking GCS; and 2) proportion of patients who sustain remission from wk 26 through wk 52. QOL will also be assessed over the 52 wks which will add to the understanding of patient experience in AAV. Other endpoints include adverse events, requirement for rescue medications, renal disease markers, GCS Toxicity Index, and Vasculitis Damage Index.
Planned enrollment is ~300 patients from 230 sites in 20 countries; enrollment expected to be completed in June 2018. The ADVOCATE trial is unique in seeking to advance a nearly GCS-free induction regimen for AAV. Details of the study design, outcome measures, and baseline patient data will be presented.
Funding
- Chemocentryx