PODO : Trial Design: Phase 2 Study of PF-06730512 in Focal Segmental Glomerulosclerosis
© 2021 International Society of Nephrology. Published by Elsevier Inc..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Kidney international reports - 6(2021), 6 vom: 04. Juni, Seite 1629-1633 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Beck, Laurence H [VerfasserIn] |
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| Links: |
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| Themen: |
Efficacy |
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| Anmerkungen: |
Date Revised 08.04.2023 published: Electronic-eCollection ClinicalTrials.gov: NCT03448692 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.ekir.2021.03.892 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Beck, Laurence H |c Jr |e verfasserin |4 aut | |
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| 520 | |a © 2021 International Society of Nephrology. Published by Elsevier Inc. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a RESULTS: This ongoing trial will report the efficacy, safety, pharmacokinetics, and biomarker results of PF-06730512 for patients with FSGS | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Berasi, Stephen P |e verfasserin |4 aut | |
| 700 | 1 | |a Copley, J Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Gorman, Donal |e verfasserin |4 aut | |
| 700 | 1 | |a Levy, Daniel I |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Chay Ngee |e verfasserin |4 aut | |
| 700 | 1 | |a Henderson, Joel M |e verfasserin |4 aut | |
| 700 | 1 | |a Salant, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Weining |e verfasserin |4 aut | |
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