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Kidney Week

Abstract: TH-PO1127

Efficacy and Safety of Ravulizumab in a Phase 2 Randomized Controlled Trial in IgA Nephropathy

Session Information

  • Late-Breaking Posters
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
  • Rocha Castilla, Jose Luis, Hospital Universitario Virgen del Rocio, Sevilla, Andalucía, Spain
  • Roccatello, Dario, University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases, Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital, University of Turin, Turin, Italy
  • Garlo, Katherine, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
  • Rice, Kara, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States
  • Lafayette, Richard A., Stanford Glomerular Disease Center, Stanford University Medical Center, Stanford, California, United States
Background

IgA nephropathy (IgAN) is the most prevalent primary glomerular disease, often progressing to ESKD. Complement activation leads to glomerular damage by immune complex deposition and release of proinflammatory cytokines. Terminal complement inhibition specifically targets the pathophysiology of IgAN and may provide improved renal outcomes.

Methods

This primary analysis of a phase 2 RCT (NCT04564339) evaluated ravulizumab (RAV) (IV; weight-based dosing Q8W) vs placebo (PBO) in adults with primary IgAN. Eligible patients (pts) (18–75 years) with biopsy-confirmed IgAN, proteinuria ≥1g/d, on stable maximally tolerated RASi with stable blood pressure ≥3 months were enrolled. The primary endpoint was % change in proteinuria from baseline to week (wk) 26 based on 24-hour urine. Secondary endpoints included spot UPCR and change in baseline eGFR at wk 26, safety, and PK/PD.

Results

66 pts were randomized 2:1 to RAV (n=43) or PBO (n=23). Mean age was 40.1 years, 46% were female, and 21% were Asian. At 26 wks, proteinuria reduction was greater with RAV vs PBO, 40.3% vs 10.9% (treatment effect 33.1%, 90% CI, 14.7%, 47.5%; p=0.0012). In RAV-treated pts, proteinuria reduction was rapid and sustained through wk 26 (Figure 1) and eGFR remained stable. RAV was well-tolerated with a safety profile similar to that of PBO and no new safety concerns (Table 1).

Conclusion

This analysis supports clinically meaningful efficacy of RAV based on rapid and sustained proteinuria reduction, providing proof-of-concept for a phase 3 trial of RAV as a potential treatment for IgAN.

Funding

  • Commercial Support – Alexion, AstraZeneca Rare Disease