Abstract: FR-PO0815
Efficacy of Ravulizumab on Proteinuria Response by Baseline Proteinuria or eGFR: Post Hoc Analysis of the SANCTUARY Trial
Session Information
- Glomerular Clinical Trials: From Data to Impact
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Farag, Youssef MK, Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Rice, Kara, Biostatistics, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Han, Seung Hyeok, Yonsei University, Seoul, Korea (the Republic of)
- Uriol Rivera, Miguel, Son Espases University Hospital, Glomerular Diseases Unit, Palma, Spain
- Chen, I-Ru, China Medical University Hospital, Taichung, Taiwan
- Kaufeld, Jessica Katharina, Hannover Medical School, Hannover, Germany
- Schreiber, Adrian, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Fenoglio, Roberta, University of Turin, Turin, Italy
- Kim, Sung Gyun, Hallym University Sacred Heart Hospital, Anyang, Korea (the Republic of)
- Kateifides, Andreas, Clinical Development, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
- Nolan, Stephen, Clinical Development, Alexion, AstraZeneca Rare Disease, Dublin, Ireland
- Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
- Lafayette, Richard A., Stanford Glomerular Disease Center, Stanford University Medical Center, Stanford, California, United States
Background
In this phase 2 randomized controlled double-blind trial (NCT04564339), adults with IgA nephropathy (IgAN) received the complement C5 inhibitor ravulizumab (RAV) (IV; q8w) or placebo (PBO) for the first 26 weeks (wk). Early and clinically meaningful reduction in proteinuria was observed. Here, we evaluate whether this benefit was independent of baseline (BL) proteinuria or estimated glomerular filtration rate (eGFR) at BL.
Methods
A post-hoc analysis assessed the impact of BL proteinuria and eGFR on treatment effect of RAV on proteinuria at wk26. A mixed model for repeated measures was used to analyze the change from BL in log-transformed spot urine protein-to-creatinine ratio (UPCR) including an interaction term for either treatment group by BL spot UPCR or treatment group by BL eGFR.
Results
In the primary model without the interaction term, wk26 UPCR reduction was –38.1% (95% CI: –48.3%, –26.0%) for RAV vs –15.3% (–34.0%, 8.8%) for PBO. In the model with treatment by BL spot UPCR interaction, reduction was similar: –38.2% (–48.3%, –26.0%) for RAV and –15.3% (–34.0%, 8.8%) for PBO. For each 1-point increase in BL spot UPCR, there was a non-significant increase of 8% in the treatment effect (interaction coefficient=0.92, P=0.6; Fig 1). Similarly, in the model with treatment by BL eGFR interaction, reduction was similar and the interaction was non-significant (interaction coefficient=0.00; P=0.8; Fig 2).
Conclusion
In this post-hoc analysis, BL proteinuria and eGFR did not significantly modify the treatment effect of RAV on proteinuria at wk26, suggesting that RAV reduces proteinuria across a range of disease severity at treatment initiation.
Funding
- Commercial Support – Alexion, Astra Zeneca Rare Disease, Boston, MA, USA