The PKD Outcomes Consortium (PKDOC) is a significant collaboration between the PKD Foundation, Critical Path Institute, representatives of the pharmaceutical industry, PKD clinicians and the U.S. Food and Drug Administration (FDA). It was created to facilitate clinical trial development for PKD therapies by establishing a clear regulatory pathway for the pharmaceutical industry to evaluate the effectiveness of potential treatments.
Why is PKDOC important?
Clinical trials are only successful with a meaningful endpoint for the disease being studied. There is no current measure of kidney function that is an accurate marker of disease progression in ADPKD. The current clinical trial endpoints are decline in estimated Glomerular Filtration Rate (eGFR) or progression to end-stage renal disease (i.e., kidney failure), both of which occur too late for drug intervention to be effective in slowing disease progression. Drug interventions would have to start much earlier and be monitored longer to see their effect on eGFR and kidney failure, making clinical studies too costly for pharmaceutical companies to pursue.
Therefore, through PKDOC, the FDA is being asked to approve the use of total kidney volume (the volume of a person’s kidney) as an indicator for human clinical trials – a more appropriate measure of disease progression in ADPKD. TKV also indicates kidney damage sooner than eGFR, so drug interventions can occur earlier when they are more likely to be effective. TKV can be measured at any point, and this information, plus age and eGFR measured at the same time, provide a prediction of patient outcome over time.
Using these three factors (TKV, age, eGFR) can help developers of clinical studies identify patient populations most appropriate for a given study, increasing the probability of the trial being successful.
The adoption of TKV as a prognostic endpoint for regulatory approval will greatly accelerate the pace of clinical research and introduction of new therapies, thereby benefiting all PKD patients.
What is a prognostic endpoint?
What progress has been made?
Through PKDOC, a new database of patient clinical data was created from three existing patient research registries (Mayo Clinic, Emory University and University of Colorado) and the CRISP (Consortium for Radiologic Imaging Studies of PKD) clinical studies. PKDOC is the largest and only database of PKD patients ever created using standardized terminology.
It will have a powerful impact on increasing clinical trials for ADPKD by serving as a guide for pharmaceutical companies to identify patients that would be the best fit to participate in a given clinical trial.
In addition, the database and disease model that exist because of PKDOC can be utilized by clinicians to better manage patient care.
PKDOC submitted the final qualification package to the FDA and European Medicines Agency (EMA) in late March of 2014. We are currently awaiting a response.
We are leading the way to find better endpoints in chronic kidney disease. PKDOC has been primarily funded through PKD Foundation fundraising efforts, an investment of more than $3 million, since 2009.