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Abstract: PO2542

PODO: Phase 2 Study of PF-06730512 in Focal Segmental Glomerulosclerosis (FSGS) - Results from First Interim Analysis

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Berasi, Stephen, Pfizer Inc, Cambridge, Massachusetts, United States
  • Copley, J. Brian, Pfizer Inc, Cambridge, Massachusetts, United States
  • Gorman, Donal, Pfizer Inc, Cambridge, United Kingdom
  • Lim, Chay Ngee, Pfizer Inc, Cambridge, Massachusetts, United States
  • Moorehead, Tara, Pfizer Inc, Cambridge, Massachusetts, United States
  • Levy, Daniel I., Pfizer Inc, Collegeville, Pennsylvania, United States
  • Hwang, Susan, Pfizer Inc, Cambridge, Massachusetts, United States
  • Geraghty, Molly, Boston University School of Medicine, Boston, Massachusetts, United States
  • Henderson, Joel M., Boston University School of Medicine, Boston, Massachusetts, United States
  • Salant, David J., Boston University School of Medicine, Boston, Massachusetts, United States
  • Lu, Weining, Boston University School of Medicine, Boston, Massachusetts, United States
Background

Focal segmental glomerulosclerosis (FSGS) is characterized by proteinuria and a histologic pattern of glomerular lesions including scarring and podocyte foot process effacement. ROBO2/SLIT2 signaling destabilizes the slit diaphragm and reduces podocyte adhesion to the glomerular basement membrane. This clinical trial evaluates efficacy and safety of ROBO2/SLIT2 inhibition with the ROBO2 fusion protein, PF-06730512, in patients with FSGS.

Methods

PODO (ClinicalTrials.gov NCT03448692) is an open-label, Phase 2a, multicenter trial in adults with FSGS, enrolling 2 cohorts (~22 each) with IV infusions of high or low dose PF-06730512 once every 2 weeks for 12 weeks. Inclusion criteria include confirmed biopsy FSGS diagnosis, suboptimal response with 1 and up to 3 drugs, eGFR ≥45 ml/min/1.73 m2 (30–45 recent biopsy), and UPCR >1.5 g/g. Exclusion criteria include collapsing FSGS, ≥50% tubulointerstitial fibrosis, and organ transplantation. The primary endpoint is change from Baseline to Week 13 in 24-hour UPCR; secondary endpoints include safety, changes in eGFR and UPCR over time (Weeks 5, 9, 13), and PF-06730512 serum concentration. Interim analyses were pre-specified. A biopsy substudy to evaluate podocyte foot process width changes is also included.

Results

The first interim analysis occurred after approximately half of the first cohort subjects completed Week 13. Modelled LS mean reduction in UPCR was 35% at Week 13 and statistically significant reductions were also observed at Week 9 and in ad hoc analysis Week 21. Exploratory data from the biopsy substudy may be presented. No safety signals have been identified for PF-06730512.

Conclusion

In this interim analysis (n=9), a significant mean reduction in UPCR was observed in FSGS subjects after 12 weeks of treatment with PF-06730512. PF-06730512 thus far is safe and well-tolerated.

Funding

  • Commercial Support – Pfizer Inc