Implementing the Kidney Health Initiative Surrogate Efficacy Endpoint in Patients With IgA Nephropathy (the PROTECT Trial)

There has been little progress in the development

and regulatory approval of novel therapies for

glomerular diseases. There are several reasons for this

dilemma, including safety and efficacy of tested therapies,

the slowly progressive nature of glomerular

diseases, challenges with clinical trial design, and the

traditional endpoints required by regulatory agencies

for drug labeling. This is compounded by the fact that

most primary glomerular diseases are recognized

internationally as rare diseases. The time required and

feasibility to conduct large-scale phase 3 clinical trials

to evaluate whether a new therapy improves kidney

survival and decreases the development of end-stage

kidney disease (ESKD) is prohibitive, particularly

when that disease is rare. Even using doubling of

serum creatinine concentration, an accepted surrogate

endpoint of ESKD, requires expensive trials with

lengthy follow-up.