Abstract: INFO20-SA
Proteinuria and GFR as Clinical Trial Endpoints In FSGS (PARASOL)
Session Information
- Informational Posters - 3
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Smith, Abigail R., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States
Group or Team Name
- PARASOL.
Description
Focal segmental glomerulosclerosis (FSGS) is a rare glomerular disease affecting adults and pediatric patients with a high risk of progression. Current treatment options have limited efficacy and cause significant side effects. There are no FDA-approved therapies and urgent need to develop safe and effective agents. Proteinuria and GFR as Clinical Trial Endpoints in Focal Segmental Glomerulosclerosis (PARASOL) is an international effort integrating observational, registry, and clinical trial data to define the relationship between eGFR and proteinuria and identify surrogate endpoints to inform feasible trial design and regulatory pathways for FSGS.
The PARASOL public workshop was sponsored by NephCure, the International Society of Glomerular Disease, the Kidney Health Initiative, the National Kidney Foundation, and the US Food and Drug Administration. Key results demonstrated that (1) mean rate of eGFR decline over 24 months was -6.9 ml/min/1.73m2/year and was associated with kidney failure after 24 months (HR=1.16, 95% CI-1.15-1.17) and (2) proteinuria at 24 months was associated with kidney failure at responder thresholds ranging from 0.3 to 1.5 g/g (adjusted HR range 0.07-0.20). Results were consistent across subgroups based on age, eGFR, and proteinuria and independently replicated in a separate cohort of participants in the United Kingdom National Registry of Rare Kidney Diseases (RaDaR). Preliminary sample size evaluation showed large treatment effects (e.g. difference in slope>5 ml/min/1.73m2/year) may be needed to attain feasible trial sample sizes (range 300-400) for eGFR outcomes; smaller effect sizes were attainable in select populations (e.g., adults, CKD stage 3). Using proteinuria response endpoints, similar sample sizes could detect differences in response as small as 15%.
PARASOL has since received additional datasets from North and South America, Europe and Asia, and analyses validating the initial results are underway. Exploration into variability of eGFR, continuous measures of proteinuria at different timepoints, and further analysis of the substantial pediatric cohort is ongoing. The PARASOL Consortium is in discussions with key stakeholders to leverage the working model and infrastructure to identify feasible and acceptable clinical trial endpoints for developing FSGS trials as well as other rare kidney diseases.
Funding
- NephCure