Kidney Week

Abstract: TH-PO0471

Evidence of a Rapid and Localized Anti-Inflammatory Effect of Ravulizumab in IgAN: Prespecified Biomarker Analysis of the I CAN Phase 3 Trial

Session Information

• Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - IgAN
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Cammett, Tobin J., Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States

Tobin J. Cammett, PhD

• Lafayette, Richard A., Stanford University Medical Center, Stanford, California, United States

Richard A. Lafayette, MD

• Farag, Youssef MK, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Youssef MK Farag, MD, PhD, MPH, FASN

• Rice, Kara, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Kara Rice, MS

• Singh, Ajay K., Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States

Ajay K. Singh, MD

• Nolan, Stephen, Alexion, AstraZeneca Rare Disease, Dublin, Ireland

Stephen Nolan

• Barratt, Jonathan, University of Leicester, Leicester, United Kingdom

Jonathan Barratt, MBChB, PhD

Background

Urinary biomarkers can provide unique insights into the mechanism of treatment effect in IgA nephropathy (IgAN). Ravulizumab (RAV) is a terminal complement C5 inhibitor that blocks formation of C5a and C5b-9. The ph3 I CAN trial (NCT06291376) is evaluating RAV in adults with IgAN.

Methods

Adults with biopsy-confirmed IgAN, eGFR ≥30, and 24h UPCR ≥0.75 g/g or UP ≥1 g/d were randomized to RAV or placebo (PBO). Primary endpoint of interim analysis: change from baseline (BL) to Week (Wk) 34 in 24h UPCR. Exploratory endpoint: soluble urine biomarkers of complement activation (terminal pathway [sC5b-9]; amplification loop [Ba]), renal macrophage infiltration (CD163), and proximal tubule injury (KIM-1), normalized to creatinine (Cr). Exploratory endpoint: resolution of hematuria (positive urine dipstick or ≥5 RBCs/hpf).

Results

At Wk34, treatment effect on 24h UPCR reduction was 43.4% for RAV vs PBO (95% CI: 33.5, 51.8; P<0.0001). Biomarker analysis included 200 patients with IgAN. BL levels of sC5b-9/Cr, Ba/Cr, CD163/Cr, and KIM-1/Cr were elevated in patients with IgAN vs normal donors (p<0.0001 for all); sC5b-9/Cr was above ULN (observed mean for normal donors + 2 SD) in 93.5% of patients. Significant reductions in biomarkers were observed with RAV vs PBO as early as Wk2, at Wk10, and all later time points (Fig 1). Among patients with hematuria at BL (RAV, n=132; PBO, n=148), the percentage with hematuria resolution was significantly greater with RAV vs PBO at Wk2, Wk10, and all later time points (Fig 2).

Conclusion

In this large, contemporary IgAN trial, terminal complement inhibition with RAV led to rapid and significant reductions in hematuria and biomarkers of glomerular inflammation and tubular damage, suggestive of a disease-modifying effect.

Acknowledgment

Medical writing support was provided by Matt Larochelle, MD, of Alexion, AstraZeneca Rare Disease (Boston, Massachusetts) and Laura J. Herold, MA, CMPP, from Citrus Health Group, Inc. (Chicago, Illinois), and was funded by Alexion, AstraZeneca Rare Disease (Boston, Massachusetts).

Funding

• Commercial Support – Alexion, AstraZeneca Rare Disease