EFFICACY AND SAFETY OF RAVULIZUMAB IN A PHASE 2 RANDOMIZED CONTROLLED TRIAL IN IgA NEPHROPATHY

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

This primary analysis of a phase 2 randomized controlled trial (NCT04564339) evaluated ravulizumab (IV; weight-based dosing Q8W) vs placebo in adults with primary IgA nephropathy. Eligible patients (pts) (18–75 years) with biopsy-confirmed IgA nephropathy, proteinuria ≥1g/day, on stable maximally tolerated renin-angiotensin system inhibitor therapy with stable blood pressure ≥3 months were enrolled. The primary endpoint was % change in proteinuria from baseline to week 26 based on 24-hour urine collection. Secondary endpoints included spot urine protein to creatinine ratio (UPCR) and change in baseline estimated glomerular filtration rate (eGFR) at week 26, safety, and pharmacokinetics/pharmacodynamics.

66 pts were randomized 2:1 to ravulizumab (n=43) or placebo (n=23). Mean age was 40.1 years, 46% were female, and 21% were Asian. At 26 weeks, proteinuria reduction was greater with ravulizumab vs placebo: 41.6% vs 16.8% reduction in urine protein (g/day) (treatment effect 29.8%, 90% CI: 9.7%, 45.5%; p=0.0059), and for UPCR (g/g), 40.3% vs 10.9% (treatment effect 33.1%, 90% CI: 14.7%, 47.5%; p=0.0012). In ravulizumab-treated pts, proteinuria reduction was rapid and sustained through week 26 (Figure 1) and eGFR remained stable. Ravulizumab was well-tolerated with a safety profile similar to that of placebo and no new safety concerns (Table 1).

Figure 1: Proteinuria in patients treated with ravulizumab and patients treated with placebo up to 26 weeks

Conclusions