PODO: Trial Design: Phase 2 Study of PF-06730512 in Focal Segmental Glomerulosclerosis

Laurence H Beck Jr; Stephen P Berasi; J Brian Copley; Donal Gorman; Daniel I Levy; Chay Ngee Lim; Joel M Henderson; David J Salant; Weining Lu

doi:10.1016/j.ekir.2021.03.892

PODO: Trial Design: Phase 2 Study of PF-06730512 in Focal Segmental Glomerulosclerosis

Kidney Int Rep. 2021 Apr 3;6(6):1629-1633. doi: 10.1016/j.ekir.2021.03.892. eCollection 2021 Jun.

Authors

Laurence H Beck Jr¹, Stephen P Berasi², J Brian Copley², Donal Gorman³, Daniel I Levy², Chay Ngee Lim², Joel M Henderson¹, David J Salant¹, Weining Lu¹

Affiliations

¹ Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts, USA.
² Pfizer Inc., Cambridge, Massachusetts, USA.
³ Pfizer Inc., Cambridge, United Kingdom.

Abstract

Introduction: Focal segmental glomerulosclerosis (FSGS) is characterized by proteinuria and a histologic pattern of glomerular lesions of diverse etiology that share features including glomerular scarring and podocyte foot process effacement. Roundabout guidance receptor 2 (ROBO2)/slit guidance ligand 2 (SLIT2) signaling destabilizes the slit diaphragm and reduces podocyte adhesion to the glomerular basement membrane (GBM). Preclinical studies suggest that inhibition of glomerular ROBO2/SLIT2 signaling can stabilize podocyte adhesion and reduce proteinuria. This clinical trial evaluates the preliminary efficacy and safety of ROBO2/SLIT2 inhibition with the ROBO2 fusion protein PF-06730512 in patients with FSGS.

Methods: The Study to Evaluate PF-06730512 in Adults With FSGS (PODO; ClinicalTrials.gov identifier NCT03448692), an open-label, phase 2a, multicenter trial in adults with FSGS, will enroll patients into 2 cohorts (n = 22 per cohort) to receive either high- or low-dose PF-06730512 (intravenous) every 2 weeks for 12 weeks. Key inclusion criteria include a confirmed biopsy diagnosis of FSGS, an estimated glomerular filtration rate (eGFR) ≥45 ml/min/1.73 m² based on the Chronic Kidney Disease Epidemiology Collaboration formula (30-45 with a recent biopsy), and urinary protein-to-creatinine ratio (UPCR) >1.5 g/g. Key exclusion criteria include collapsing FSGS, serious/active infection, ≥50% tubulointerstitial fibrosis on biopsy, and organ transplantation. The primary endpoint is change from baseline to week 13 in UPCR; secondary endpoints include safety, changes in eGFR, and PF-06730512 serum concentration.

Results: This ongoing trial will report the efficacy, safety, pharmacokinetics, and biomarker results of PF-06730512 for patients with FSGS.

Conclusion: Findings from this proof-of-concept study may support further development and evaluation of PF-06730512 to treat FSGS and warrant assessment in phase 3 clinical trials.

Keywords: ROBO2; efficacy; focal segmental glomerulosclerosis; pharmacokinetics; safety; trial in progress.

Associated data

ClinicalTrials.gov/NCT03448692

Abstract

Associated data

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