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.
Professor Barratt leads the Renal Research Group within the College of Life Sciences, University of Leicester. His research is focused on a bench to bedside approach to improving our understanding of the pathogenesis of IgA nephropathy a common global cause of kidney failure. Jonathan is the IgA nephropathy Rare Disease Group lead for the UK National Registry of Rare Kidney Diseases (RaDaR) and a member of the steering committee for the International IgA Nephropathy Network. He works closely with pharmaceutical companies interested in new treatments for IgA nephropathy, and is Chief Investigator for a number of international randomised controlled Phase 2 and 3 clinical trials in IgA nephropathy, and a member of the FDA and American Society of Nephrology Kidney Health Initiative: Identifying Surrogate Endpoints for Clinical Trials in IgA Nephropathy Work group.
Dr. Carroll received his Masters in Applied Statistics with Distinction from Sheffield Hallam University, UK and his PhD entitled "Statistical Issues in Oncologic Clinical Drug Development" from the University of East Anglia, UK. He is currently an Honorary Senior Lecturer in Medical Statistics at the University of Sheffield, UK. He joined AstraZeneca (then ICI) Pharmaceuticals in the late 80's and rose to the position of VP Statistics and Chief Statistician in the second half of the 2000's.
Dr. Carroll has extensive experience in the design, conduct, analysis and reporting of clinical trials. During his career, he has developed, published and applied innovative, novel statistical methodologies and gained hands on experience in the parametric modelling of survival data and the application of adaptive and Bayesian approaches to trial design and analysis. As a consultant this includes the use of novel decision-based designs in Phase II trials and dose ranging studies to aid effective decision making, and the use of complex staged designs in pivotal Phase II/III and Phase III trials to expedite overall drug development times.
Dr. Jonathan Hogan is an Assistant Professor of Medicine, Division of Nephrology, at the Perelman School of Medicine, University of Pennsylvania, in Philadelphia, PA. He is the clinical director of the Penn Glomerular Disease Center and also runs the Penn Onconephrology Program. He is site-PI on multiple industry and NIH-sponsored trials and studies in glomerular diseases and diabetic nephropathy. He has published multiple peer-reviewed manuscripts and book chapters on glomerular diseases and onconephrology, and has been an invited speaker on these topics at regional, national and international meetings.
Dr. Hogan was born and raised in Queens, New York. He received Bachelors Degrees in Philosophy and Biology at Fordham University in the Bronx, New York. He received his medical degree from the University of Pennsylvania in Philadelphia, PA, and completed his internship and residency in Internal Medicine at the Hospital of the University of Pennsylvania. He then completed his fellowship in Nephrology at Columbia University Medical Center, and a subspecialty fellowship in Glomerular Diseases at the Columbia University Glomerular Center.
Laura H. Mariani, MD, MS, is a nephrologist and researcher at the University of Michigan Division of Nephrology. She completed her medical school training at the University of Michigan and subsequently completed her internal medicine residency, chief residency, nephrology fellowship, and Masters of Science in Clinical Epidemiology at the University of Pennsylvania.
Dr. Mariani is currently an Assistant Professor in the Division of Nephrology at the University of Michigan. She has a primary clinical and research interest in observational studies in glomerular disease. She is involved in several clinical and translational NIH-funded research studies in kidney disease. Her research is focused on developing and applying statistical methods for clinical outcome definition and prediction of kidney disease progression as well as linking clinical phenotype to novel biomarkers and high dimensional omics data to better understand disease mechanisms that can be targeted for therapy in glomerular disease.
