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Abstract: INFO23

PODO: A Phase 2 Multicenter, Open-Label, Adaptive, Sequential Cohort Trial of PF-06730512 in Adult Subjects with Focal Segmental Glomerulosclerosis (FSGS)

Session Information

Category: Glomerular Diseases

  • No subcategory defined

Authors

  • Berasi, Stephen, Pfizer Inc, Cambridge, Massachusetts, United States
  • Fornoni, Alessia, University of Miami, Coral Gables, Florida, United States
  • Lafayette, Richard A., Stanford University School of Medicine, Stanford, California, United States
  • Tumlin, James A., Emory University, Atlanta, Georgia, United States
  • Ayoub, Isabelle, Ohio State University, Columbus, Ohio, United States
  • Mandayam, Sreedhar A., University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • McMahon, Alan W., University of Alberta, Edmonton, Alberta, Canada
  • Awad, Ahmed M., University of Missouri Kansas City, Kansas City, Missouri, United States
  • Rizk, Dana, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Peev, Vasil, Rush University Medical Center, Chicago, Illinois, United States
  • Kamil, Elaine S., Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Vincenti, Flavio, University of California San Francisco, San Francisco, California, United States
  • Mottl, Amy K., University of North Carolina Kidney Center, Chapel Hill, North Carolina, United States
  • El-Shahawy, Mohamed A., Keck Hospital of USC, Los Angeles, California, United States
  • Levy, Daniel I., Pfizer Inc, Cambridge, Massachusetts, United States
  • Gorman, Donal, Pfizer Inc, Cambridge, Massachusetts, United States
  • Copley, J. Brian, Pfizer Inc, Cambridge, Massachusetts, United States
Description

Focal Segmental Glomerulosclerosis (FSGS) is associated with altered interaction between podocytes and the glomerular basement membrane (GBM), resulting in podocyte injury, foot process effacement, and damage to the filtration barrier. ROBO2/SLIT2 signaling negatively regulates nephrin-induced actin polymerization and destabilizes podocyte focal adhesions and attachment to the GBM by inhibiting non-muscle myosin IIA. PF-06730512 is a SLIT ligand trap consisting of a fusion protein between a portion of ROBO2 and a human immunoglobulin fragment. Neutralization of ROBO2 may protect the podocyte from injury and have therapeutic implications for FSGS.

PODO is an open-label Phase 2 multicenter trial in adult subjects (> 18 years) with FSGS. The trial consists of 2 cohorts, enrolling 22 subjects in each, to investigate two different doses of PF-06730512 administered intravenously every two weeks for 12 weeks. To be eligible, subjects must have a confirmed biopsy diagnosis of FSGS, an eGFR of >45 ml/min/1.73m2, a UPCR >1.5 g/g, and must have been treated with at least 1 but not more than 3 classes of immunosuppressants either alone or in combination, or must have a contraindication or intolerance to an immunosuppressant per investigator judgment. An eGFR between 30-45 ml/min/1.73m2 is allowed if a biopsy within 12 months of screening demonstrates < 50% tubulointerstitial fibrosis. Exclusions include collapsing FSGS, serious infection, >50% tubulointerstitial fibrosis on biopsy, prior heroin use and organ transplantation. Additional eligibility criteria are listed on https://clinicaltrials.gov/ct2/show/NCT03448692. The primary endpoint is the percentage change from baseline in UPCR to Week 13 following drug administration. Secondary endpoints include safety and changes in eGFR.

The PODO trial will provide information about the efficacy and safety of PF-06730512 inhibition of the ROBO2 pathway and its impact on podocyte injury in FSGS.

Funding

  • Pfizer Inc