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Kidney Week

Abstract: PO2539

Effect of Avacopan, a Selective C5a Receptor Inhibitor, on C3G Histologic Index of Disease Chronicity

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Bomback, Andrew S., Columbia University Irving Medical Center, New York, New York, United States
  • Herlitz, Leal C., Cleveland Clinic, Cleveland, Ohio, United States
  • Yue, Huibin, ChemoCentryx Inc, San Carlos, California, United States
  • Kedia, Priyanka Punit, ChemoCentryx Inc, San Carlos, California, United States
  • Schall, Thomas J., ChemoCentryx Inc, San Carlos, California, United States
  • Bekker, Pirow, ChemoCentryx Inc, San Carlos, California, United States
Background

Complement 3 Glomerulopathy (C3G) is a rare kidney disorder with no approved treatment presenting with proteinuria, hematuria, renal insufficiency, and/or hypertension.

Methods

In the randomized, double-blind, placebo-controlled ACCOLADE study, patients were randomized 1:1 to receive avacopan 30 mg twice daily (n=28) or placebo (n=29) for 26 weeks; thereafter (still blinded as to original treatment) consenting patients (25 each in avacopan and placebo groups) received avacopan for another 26 weeks.

The C3G Histologic Index (C3HI) was used to evaluate changes in kidney histology. C3HI of Disease Activity, measuring acute glomerular inflammation, was the primary efficacy measure; change in the C3HI of Disease Chronicity, measuring chronic indices such as fibrosis, was a secondary endpoint.

Results

Mean baseline C3HI of Disease Chronicity was 4.7 and 4.2 (out of 10) in the avacopan and placebo groups, respectively. Mean % change from baseline in the C3HI of Disease Chronicity (greater score denotes greater fibrosis progression) through week 26 was 31.7% with avacopan (N=26) vs 57.5% with placebo (N=26); change of 0.8 vs 1.6, respectively, P=0.04 (Table 1).

Subsequent assessment of paired biopsies from weeks 26 and 52 (in 17 and 16 patients, avacopan and placebo, respectively) revealed that patients continuously on avacopan had a similar rate of change in the second 26 weeks vs. the first 26 weeks (14.4% vs 12.6%), while patients who switched from placebo to avacopan for the second 26 weeks showed a significant improvement inflection (-2.3%; P=0.0083, Figure 1).

Conclusion

Avacopan attenuated C3G progression. The change in C3HI of Disease Chronicity was lower with avacopan compared to placebo and also improved in patients who switched from placebo to avacopan.

Figure 1. Paired Profiles for Change in C3HI of Disease Chronicity (Baseline to Wk 26, Wk26 to Wk52) in Former Placebo Group

Funding

  • Other U.S. Government Support