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
- Clinical/Diagnostic Renal Pathology and Lab Medicine - II
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
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 Prednisone | Avacopan + LD Prednisone | Avacopan + No Prednisone | ||||||||||
Time | 95% CI | 95% CI | 95% CI | |||||||||
Points | N= | Geomean | Lower | Upper | N= | Geomean | Lower | Upper | N= | Geomean | Lower | Upper |
Pre dose | 19 | 258 | 148 | 448 | 21 | 408 | 280 | 596 | 18 | 250 | 137 | 458 |
Day 8 | 19 | 300 | 186 | 485 | 21 | 300* | 207 | 436 | 18 | 180* | 110 | 296 |
Day 15 | 19 | 249 | 147 | 423 | 21 | 213*** | 142 | 321 | 18 | 165* | 89 | 306 |
Day 29 | 19 | 220 | 141 | 342 | 21 | 117*** | 78 | 173 | 17 | 117** | 63 | 216 |
Day 57 | 19 | 116*** | 74 | 182 | 20 | 115*** | 70 | 188 | 16 | 125# | 71 | 219 |
Day 85 | 19 | 120** | 77 | 187 | 20 | 85*** | 50 | 145 | 18 | 97* | 50 | 188 |
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 –