Background/Purpose: CCX168 is a potent, specific C5aR inhibitor in clinical development for ANCA-associated vasculitis. The initial focus of this randomized, double-blind, placebo-controlled clinical trial was on renal disease activity, since CCX168 showed profound efficacy in a mouse model of MPO ANCA-induced glomerulonephritis. CCX168 indeed showed renal disease efficacy of oral 30 mg CCX168 given twice daily for 12 weeks based on eGFR (up to 6.8 mL/min/1.73 m2 increase over 12 weeks), urinary ACR (mean decrease up to 63% over 12 weeks), and MCP-1:creatinine (up to 72% decrease over 12 weeks).
Methods: The purpose of this investigation was whether CCX168 treatment also has any effect on non-renal disease activity. The Birmingham Vasculitis Activity Index (BVAS) is a global disease activity index. Efficacy based on BVAS was evaluated to assess the potential non-renal disease activity of CCX168. 25 patients completed this clinical trial; 9 received placebo+cyclophosphamide (CYC)+full dose prednisone (60 mg/day), 8 received CCX168+CYC+low dose prednisone (20 mg/day), and 8 received CCX168+CYC+no prednisone.
Results: Baseline characteristics and Week 12 results on renal and non-renal disease activity are shown in the table.
|
CCX168+CYC+Low-Dose Steroids (N=8) |
CCX168+CYC+No Steroids (N=8) |
SOC: CYC+High-Dose Steroids (N=9) |
||
| Baseline Characteristics | ||||
| Age, years | mean (SD) | 55.3 (16.3) | 54.9 (15.0) | 57.7 (14.0) |
| Gender, M/F | % | 70/30 | 50/50 | 50/50 |
| Duration of ANCA disease, months | median (range) | 0.5 (0-162) | 0 (0-53) | 0 (0-32) |
| ANCA disease status, new/relapsed | % | 70/30 | 75/25 | 88/12 |
| Anti-MPO/Anti-PR3 positive | % | 40/60 | 63/37 | 63/37 |
| BVAS | median (range) | 11 (5-30) | 11 (5-28) | 9 (3-15) |
| eGFR, ml/min/1.73 m2 | mean (SD) | 56.8 (14.6) | 52.4 (17.7) | 56.9 (25.2) |
| U-Albumin:creatinine ratio, mg/g | mean (SD) | 386 (346) | 341 (287) | 417 (416) |
| Efficacy Results | ||||
| Steroids rescue events | n (%) | 0 (0%) | 1 (13%) | 1 (11%) |
| eGFR change at Wk 12, ml/min/1.73 m2 | mean (SEM) | 6.8 (2.1) | 0.6 (3.6) | 2.2 (3.3) |
| U-ACR % change at Wk 12 | mean | -63% | -59% | -9% |
| U-MCP-1:creatinine % change at Wk 12 | mean | -72% | -52% | -37% |
| BVAS Total | ||||
| Response* at Wk 12 | % of pts | 86% | 88% | 44% |
| Remission** at Wk 12 | % of pts | 29% | 25% | 33% |
| BVAS Renal | ||||
| Response at Wk 12 | % of pts | 71% | 50% | 38% |
| Remission at Wk 12 | % of pts | 29% | 25% | 25% |
| BVAS Non-Renal | ||||
| Response at Wk 12 | % of pts | 83% | 88% | 57% |
| Remission at Wk 12 | % of pts | 67% | 50% | 43% |
| BVAS Total %Change at Wk12 | mean ± SEM | -71 ± 9% | -65 ± 11% | -26 ± 25% |
| BVAS Renal %Change at Wk12 | mean ± SEM | -64 ± 10% | -50 ± 15% | -16 ± 26% |
| BVAS Non-Renal %Change at Wk12 | mean ± SEM | -81 ± 33% | -83 ± 29% | -15 ± 6% |
| * Response: BVAS decrease ≥50% plus no worsening in any body system; ** Remission: BVAS of 0 plus prednisone dose ≤10 mg/day. |
Conclusion: In addition to an effect on renal disease activity, CCX168 treatment of patients with ANCA-associated vasculitis also resulted in a salutory effect on non-renal disease activity based on the non-renal component of the BVAS.
Disclosure:
P. Bekker,
Chemocentryx,
1,
Chemocentryx,
3;
D. Jayne,
Chemocentryx,
5;
A. Bruchfeld,
Chemocentryx,
5;
M. Schaier,
None;
K. Ciechanowski,
None;
L. Harper,
Chemocentryx,
5;
M. Jadoul,
None;
M. Segelmark,
Chemocentryx,
5;
D. Selga,
None;
I. Szombati,
None;
M. Venning,
Chemocentryx,
5;
C. Hugo,
None;
P. L. V. Daele,
None;
O. Viklicky,
None;
A. Potarca,
Chemocentryx,
1,
Chemocentryx,
5;
T. J. Schall,
Chemocentryx,
1,
Chemocentryx,
6,
Chemocentryx,
3.
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/ccx168-an-orally-administered-c5ar-inhibitor-for-treatment-of-patients-with-antineutrophil-cytoplasmic-antibody-associated-vasculitis/