New Endpoints for CKD Clinical Trials Gaining Traction with Regulators

AJKD Gives Free Access to Endpoint Data and Commentaries

New York, NY (November 10, 2014) – New targets for endpoints in clinical trials in chronic kidney disease patients are being proposed in Europe and could be a harbinger of future changes in the study of CKD therapies in the United States.

The development stems from a National Kidney Foundation (NKF) and US Food and Drug Administration (FDA) co-sponsored a workshop titled "GFR Decline as an Endpoint for Clinical Trials in CKD". In preparation for the workshop the planning committee performed extensive meta-analyses on both observational and clinical trial data that included over 1.5 million study subjects. Based on a critical examination of the data, the workshop participants recommended that 40% decline in Glomerular Filtration Rate (GFR) would be an acceptable clinical end point to evaluate therapeutic efficacy in some clinical trial designs in CKD.  Even a 30% decline in eGFR might be considered an appropriate clinical endpoint in certain circumstances.

For a limited time, the American Journal of Kidney Diseases is providing free access to the entire series of articles describing the workshop conclusions and the analyses that were performed to support the use of lesser changes in kidney function as end points in clinical trials of CKD. All of the articles can be found under the "NKF-FDA Workshop Articles" tab on www.ajkd.org or by visiting, http://www.ajkd.org/content/nkffdaworkshop.

The publication of the papers coincides with the release of the European Medicines Agency (EMA) draft guidelines that will govern clinical trials of medicines aimed at preventing and slowing the progression of CKD. The EMA's draft guidelines incorporates the targets identified in NKF/FDA joint conference and is a bellwether of wider acceptance among regulators, researchers and clinicians, that a decline in GFR between 30-40% is an acceptable primary efficacy end point.

"What we're seeing here is a real paradigm shift," said Kerry Willis, Chief Scientific Officer of the National Kidney Foundation. "This is the first time in many years we've seen an evolving view of clinical endpoints in CKD trials. This could advance the development of new therapeutics and research initiatives that will prolong lives and prevent the progression of CKD."

Prior to the joint NKF/FDA workshop, halving of GFR, assessed as a doubling of serum creatinine levels, was considered an acceptable surrogate endpoint for the development of kidney failure. Using a lesser decline in GFR, such as 40 or 30 percent, has the potential to decrease the size, duration, and cost of clinical trials and could extend benefits to patients in the earlier phases of CKD.

The NKF/FDA Scientific Workshop, "GFR Decline as an Endpoint for Clinical Trials in CKD" was the result of the year-long efforts of a Planning Committee chaired by Dr. Andrew Levey of Tufts Medical Center and Dr. Aliza Thompson of the FDA, and Dr. Josef Coresh, Chair of the Analytic Group. The 130 workshop attendees included clinical trial and epidemiology experts; regulatory and government representatives from the European Medicines Agency, National Institutes of Health, Critical Path Institute, the FDA; dialysis and pharmaceutical industry representatives; and other professional organizations, including the American Diabetes Association and the Polycystic Kidney Disease Foundation.

"This workshop was really a model for how patient advocacy organizations can bring clinicians and regulators together to enhance research and development of new therapeutics," said Dr. Levey. "We're already beginning to see action as a result of this workshop and we hope this will usher in a new era of therapies and treatments that will slow the progression of kidney disease, reduce complications and improve patient outcomes."

For more information on the workshop and proposed endpoints, please visit the special AJKD section, http://www.ajkd.org/content/nkffdaworkshop.

The National Kidney Foundation (NKF) is the leading organization in the U.S. dedicated to the awareness, prevention and treatment of kidney disease for hundreds of thousands of healthcare professionals, millions of patients and their families and tens of millions of Americans at risk. For more information on kidney health, visit kidney.org.