Abstract: FR-PO745

Rapid Reduction in Urinary sCD163 Correlates with Clinical Benefit in the CLEAR Study of C5aR Inhibitor Avacopan in ANCA-Associated Vasculitis

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Deng, Jun, ChemoCentryx, Inc, Mountain View, California, United States
  • Potarca, Antonia, ChemoCentryx, Inc, Mountain View, California, United States
  • Schall, Thomas J., ChemoCentryx, Inc, Mountain View, California, United States
  • Bekker, Pirow, ChemoCentryx, Inc, Mountain View, California, United States
Background

Avacopan (CCX168), a potent C5aR inhibitor, induced rapid clinical benefit (measured by BVAS, proteinuria, and health-related quality of life measurements) in the Phase 2 CLEAR trial in ANCA-associated vasculitis, AAV (Jayne et al, JASN, 2017). Urinary soluble CD163 (sCD163) is a macrophage cell surface molecule known to correlate with renal histopathology, and it is a useful biomarker of kidney inflammation in AAV (O’Reilly et al, JASN, 2016). We evaluated urinary sCD163 in CLEAR patients at baseline and over the 12-week treatment period.

Methods

CLEAR comprised 3 patient groups: (1)Full dose prednisone (60 mg), standard care; (2)Avacopan 30 mg b.i.d. plus low dose prednisone (20 mg); (3)Avacopan 30 mg b.i.d. plus no prednisone. All patients received either IV cyclophosphamide or IV rituximab. sCD163 (ELISA) and creatinine were measured pre-dose, and days 8, 15, 29, 57, and 85.

Results

Avacopan treatment reduced sCD163/creatinine markedly by day 8, and further over the course of 12-weeks (see table). By contrast, standard care controls with full-dose prednisone therapy did not show improvement in urinary sCD163 until day 57. The urinary sCD163/creatinine levels were highly correlated with previously reported improvements in urinary albumin/creatinine ratio and MCP-1/creatinine ratio (p<0.0001).

Conclusion

Avacopan induced a rapid reduction of sCD163, which correlated with similarly rapid improvements of kidney inflammation markers and AAV signs and symptoms in the CLEAR trial. sCD163 may provide a valuable biomarker of clinical improvements derived from avacopan. Avacopan is currently in a Phase 3 clinical trial for AAV.

Urine sCD163/creatinine ng/mmole
 Placebo + FD PrednisoneAvacopan + LD PrednisoneAvacopan + No Prednisone
Time  95% CI  95% CI  95% CI
PointsN=GeomeanLowerUpperN=GeomeanLowerUpperN=GeomeanLowerUpper
Pre dose192581484482140828059618250137458
Day 81930018648521300*20743618180*110296
Day 151924914742321213***14232118165*89306
Day 291922014134221117***7817317117**63216
Day 5719116***7418220115***7018816125#71219
Day 8519120**771872085***501451897*50188

Paired t-test against baseline in each group: *p<0.05; **p<0.01; ***p<0.001; # p=0.076; FD = Full dose; LD = Low dose

Funding

  • Other NIH Support