Understanding Innovative Endpoints in Glomerular Diseases
Glomerular disease represents a major cause of end-stage kidney disease (ESKD). Despite the clear unmet need, there has been little progress in the study of therapeutics for glomerular diseases. The currently accepted clinical endpoints used in randomized controlled trials (RCTs) rely on late-stage manifestations of disease (i.e. ESKD or doubling serum creatinine) and require large, costly trials of long duration to demonstrate statistical significance. As a result, the idea of surrogate endpoints to overcome hurdles in the study of glomerular disease has gained increasing popularity.
In 2018, significant progress was made in the NKF/FDA/EMA workshop, concluding that early changes in albuminuria and estimated glomerular filtration rate (eGFR) slope meet the criteria for surrogate endpoints in patients with chronic kidney disease. Further work has been conducted specifically in rare glomerular diseases; in immunoglobulin A nephropathy (IgAN), data support the reduction of proteinuria as a surrogate endpoint in clinical trials. In focal segmental glomerulosclerosis (FSGS), obtaining partial or complete proteinuria remission identifies patients with better renal outcomes; the definition of partial remission has since been redefined and allows for earlier prediction of clinical endpoints.
Tune in to hear the experts discuss these recent developments in innovative endpoints and their impact on RCT design in IgAN and FSGS.