Abstract: FR-OR107
Effects of Ravulizumab on Proteinuria and Hematuria in Patients with IgAN: A Prespecified Interim Analysis of the Phase 3 I CAN Trial
Session Information
- High-Impact Clinical Trials
October 23, 2026 | Location: Bluebird Ballroom, Convention Center
Abstract Time: 12:15 PM - 12:30 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Lafayette, Richard A., Stanford University Medical Center, Stanford, California, United States
- Farag, Youssef MK, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Rice, Kara, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Cammett, Tobin J., Alexion, AstraZeneca Rare Disease, New Haven, Connecticut, United States
- Inker, Lesley, Tufts Medical Center, Boston, Massachusetts, United States
- Trimarchi, Hernan, Hospital Britanico de Buenos Aires, Buenos Aires, Argentina
- Bruchfeld, Annette, Linkopings universitet, Linköping, Sweden
- Heerspink, Hiddo Jan L., University of Groningen, University Medical Center Gronigen, Groningen, Netherlands
- Liew, Adrian, Mount Elizabeth Novena Hospital, Singapore, Singapore
- Carroll, Kevin, KJC Statistics, Dublin, Ireland
- Zhang, Hong, Peking University First Hospital, Beijing, China
- Norouzi, Sayna, Loma Linda University Medical Center, Loma Linda, California, United States
- Hou, Shuang, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Park, Sehoon, Seoul National University Hospital, Seoul, Korea (the Republic of)
- Pérez Valdivia, Miguel Angel, UGC Urología-Nefrología, Hospital Virgen del Rocío, Seville, Spain
- Radhakrishnan, Jai, New York-Presbyterian/Columbia University Irving Medical Center, New York, New York, United States
- Suzuki, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
- Schneider, Bonnie, IgA Nephropathy Foundation, Wall, New Jersey, United States
- Marsala, John, IgA Nephropathy Patient Advocate, Westbury, New York, United States
- Carrillo Infante, Cynthia, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Lake, Stephen, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Singh, Ajay K., Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Nolan, Stephen, Alexion, AstraZeneca Rare Disease, Dublin, Ireland
- Barratt, Jonathan, University of Leicester, Leicester, England, United Kingdom
Group or Team Name
- I CAN Study Group
Background
Complement activation plays a central role in IgA nephropathy (IgAN), driving inflammation, nephron loss, and kidney failure. I CAN is a phase 3, randomized, double-blind, placebo-controlled global study of ravulizumab (RAV) in adults with primary IgAN (NCT06291376). Ravulizumab (RAV) is a terminal complement inhibitor approved in four other indications. Here, we report the primary findings from our interim analysis (IA).
Methods
Adults with biopsy-proven IgAN, eGFR ≥30, and 24h UPCR ≥0.75 g/g or UP ≥1 g/d were randomized to RAV or placebo (PBO). Wk 34 summary measures included proportion of patients (pts) with ≥50% reduction in 24h UPCR, partial remission (24h UP <1 g/d and ≥25% reduction), complete remission (24h UP <0.3 g/d), and new-onset hematuria.
Results
In the IA efficacy dataset of 352 pts (mean age 42.5 y; 148 females), RAV reduced UPCR as early as Wk 10; at Wk 34, 24h UPCR was significantly reduced vs PBO (treatment effect 43.4%, 95% CI: 33.5-51.8; P<0.0001). Reductions were generally consistent across subgroups (eg, Asian and non-Asian sites). Compared with PBO, the RAV group had significantly higher rates of pts achieving ≥50% reduction from baseline 24h UPCR, partial remission, and complete remission (Fig 1). In pts without baseline hematuria, new-onset hematuria was significantly lower with RAV vs PBO at Wk 34 (Fig 2). Safety in the RAV group was comparable to placebo; no meningococcal infections or deaths occurred. Effects of RAV on inflammatory biomarkers were observed as soon as Wk 2 and were sustained over the treatment period.
Conclusion
RAV demonstrated rapid, clinically meaningful, and statistically significant reductions in UPCR. Favorable effects on hematuria, biomarkers, along with remission rates strongly support a disease modifying anti-inflammatory effect of terminal complement inhibition with RAV.
Acknowledgment
Medical writing support was provided by Alison Thomas, PharmD, from Citrus Health Group, Inc. (Chicago, Illinois), and was funded by Alexion, AstraZeneca Rare Disease (Boston, Massachusetts).
Funding
- Commercial Support – Alexion, AstraZeneca Rare Disease