Efficacy and Safety of Ravulizumab in IgA Nephropathy: A Phase 2 Randomized Double-Blind Placebo-Controlled Trial.
A randomised trial found that ravulizumab, a long-acting drug that blocks part of the immune system's complement cascade, reduced protein leakage in the urine of people with IgA nephropathy and appeared to hold kidney function steady over six months. It was generally well tolerated, and a larger phase 3 trial is now under way.
Background
The complement system is central to the pathogenesis of IgA nephropathy. Ravulizumab is a long-acting monoclonal antibody that inhibits complement C5, providing sustained blockade of the terminal complement pathway, and was tested here on top of standard of care.
Study design
Adults with IgA nephropathy, proteinuria of at least 1 g/day, eGFR of at least 30 ml/min per 1.73 m2 and stable renin-angiotensin blockade were randomised 2:1 to intravenous ravulizumab every 8 weeks (43 patients) or placebo (23 patients) for 26 weeks, followed by open-label ravulizumab for all participants from week 26 to week 50. The primary end point was percentage change in proteinuria from baseline to week 26.
Key findings
At week 26, urine protein changed by -41.9% (95% CI -50.2% to -32.0%) with ravulizumab versus -16.8% (95% CI -31.8% to 1.6%) with placebo, a 30.1% treatment effect (P = 0.005). By week 50 the change from baseline with ravulizumab was -44.8% (95% CI -55.1% to -32.1%). Least squares mean change in eGFR to week 26 was 0.2 ml/min per 1.73 m2 with ravulizumab versus -4.5 ml/min per 1.73 m2 with placebo.
Safety
Ravulizumab was well tolerated, with an adverse event profile reported as similar to that of placebo across the trial.
Category
Research
Source
Journal of the American Society of Nephrology (JASN)
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