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Kidney Week

Abstract: INFO37

TRACTION-2 Study: Safety and Efficacy Evaluation of GFB-887, a TRPC5 Channel Inhibitor, in Patients With DN, FSGS, or TR-MCD

Session Information

  • Informational Posters
    November 04, 2021 | Location: On-Demand, Virtual Only
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • No subcategory defined

Authors

  • Farag, Youssef MK, Goldfinch Bio Inc, Cambridge, Massachusetts, United States
  • Lawler, John, Goldfinch Bio Inc, Cambridge, Massachusetts, United States
  • Cornwall, Caitlin, Goldfinch Bio Inc, Cambridge, Massachusetts, United States
  • Johnson, Leslie, Goldfinch Bio Inc, Cambridge, Massachusetts, United States
  • Gaich, Gregory A., Goldfinch Bio Inc, Cambridge, Massachusetts, United States
Description

Activation of the TRPC5-Rac1 pathway in podocytes is a key driver of podocytopathies such as focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), and diabetic nephropathy (DN). GFB-887 is a small molecule TRPC5 ion channel inhibitor that has been shown in preclinical models to prevent podocyte damage mediated by Rac1 signaling. In a first-in-human study, single doses of up to 900 mg of GFB-887 were well-tolerated with a favorable PK profile in healthy participants. GFB-887 exhibited dose-dependent reductions in urinary Rac1 (uRac1), indicating that GFB-887 engages TRPC5 in the podocytes and inhibits the TRPC5-Rac1 pathway.

TRACTION-2 is a phase 2, double-blind, placebo-controlled, multiple-ascending dose study of GFB-887 in patients with FSGS, treatment resistant-MCD, or DN (NCT04387448). Adult patients on stable renin angiotensin system blockade and/or immunosuppression with persistent proteinuria will be randomized and dosed in 3 ascending dose levels of GFB-887 or placebo for 12 weeks. Cohorts may be expanded or biomarker enriched based on an adaptive interim analysis. The primary objective is to evaluate the effect of GFB-887 on proteinuria. Safety and tolerability, quality of life, PK/PD profiles, and the association between uRac1 levels and efficacy will be evaluated.

Participants in all dose levels will undergo a 4-week screening period, a run-in period of up to 2 weeks, a 12- week treatment period, followed by an 8-week off drug washout period. The first cohort will consist of 8 participants and subsequent cohorts will include a total of 48 participants with DN and 30 participants with either FSGS or TR-MCD. Several measures are in place to mitigate potential disruptions in study activities due to the ongoing COVID-19 pandemic. These measures included alternative methods to conduct study visits, including assessments at the patient’s home using a home healthcare nurse, via telephone, or using other telemedicine options; and use of a symptom-directed physical examination for visits conducted via home nursing or telemedicine.

Results from this study will provide evidence that blockade of TRPC5-Rac1 pathway with GFB-887 is an effective strategy to treat patients with podocytopathies and guide the next phase of clinical development of GFB-887.

Funding

  • Goldfinch Bio