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