Safety and Efficacy of GFB-887, a TRPC5 Channel Inhibitor, in Patients With Focal Segmental Glomerulosclerosis, Treatment-Resistant Minimal Change Disease, or Diabetic Nephropathy: TRACTION-2 Trial Design.

Autor:	Walsh L; Goldfinch Bio, Inc., Cambridge, Massachusetts, USA., Reilly JF; Goldfinch Bio, Inc., Cambridge, Massachusetts, USA., Cornwall C; Goldfinch Bio, Inc., Cambridge, Massachusetts, USA., Gaich GA; Goldfinch Bio, Inc., Cambridge, Massachusetts, USA., Gipson DS; University of Michigan, Ann Arbor, Michigan, USA., Heerspink HJL; University of Groningen, Groningen, Netherlands., Johnson L; Goldfinch Bio, Inc., Cambridge, Massachusetts, USA., Trachtman H; NYU Langone Health, New York, New York, USA., Tuttle KR; Providence Health Care, Spokane, WA.; University of Washington, Seattle, Washington, USA., Farag YMK; Goldfinch Bio, Inc., Cambridge, Massachusetts, USA., Padmanabhan K; Cytel, Waltham, Massachusetts, USA., Pan-Zhou XR; Goldfinch Bio, Inc., Cambridge, Massachusetts, USA., Woodworth JR; Goldfinch Bio, Inc., Cambridge, Massachusetts, USA., Czerwiec FS; Goldfinch Bio, Inc., Cambridge, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	Kidney international reports [Kidney Int Rep] 2021 Jul 23; Vol. 6 (10), pp. 2575-2584. Date of Electronic Publication: 2021 Jul 23 (Print Publication: 2021).
DOI:	10.1016/j.ekir.2021.07.006
Abstrakt:	Introduction: A critical unmet need exists for precision therapies for chronic kidney disease. GFB-887 is a podocyte-targeting, small molecule inhibitor of transient receptor potential canonical-5 (TRPC5) designed specifically to treat patients with glomerular kidney diseases characterized by an overactivation of the TRPC5-Rac1 pathway. In a first-in-human study, GFB-887 was found to be safe and well tolerated, had a pharmacokinetic (PK) profile allowing once-daily dosing, and dose dependently decreased urinary Rac1 in healthy adults. Methods: TRACTION-2 is a phase 2a, double-blind, placebo-controlled, multiple-ascending dose study of GFB-887 in patients with focal segmental glomerulosclerosis (FSGS), treatment-resistant minimal change disease (TR-MCD), or diabetic nephropathy (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 to GFB-887 or placebo for 12 weeks. Cohorts may be expanded or biomarker-enriched depending upon results of an adaptive interim analysis. Results: The primary objective is to evaluate the effect of increasing doses of GFB-887 on proteinuria. Safety and tolerability, quality of life, pharmacokinetic/pharmacodynamic profiles, and the potential association of urinary Rac1 with efficacy will also be evaluated. The projected sample size has 80% power to detect a treatment difference in proteinuria of 54% (FSGS/TR-MCD) or 44% (DN) compared to placebo. Conclusion: TRACTION-2 will explore whether targeted blockade of the TRPC5-Rac1 pathway with GFB-887 is an efficacious and safe treatment strategy for patients with FSGS, TR-MCD, and DN and the potential value of urinary Rac1 as a predictive biomarker of treatment response. (© 2021 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)
Databáze:	MEDLINE
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