TRPC6 Inhibition for the Treatment of FSGS: Phase 2 Randomized Controlled Trial of BI 764198
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Le résumé fourni par la source
Background: Focal segmental glomerulosclerosis (FSGS) is a relevant histopathological finding in individuals presenting with proteinuria, resulting in kidney failure in 50% within 5–10 years. In FSGS, transient receptor potential cation channel, subfamily-C, member-6 (TRPC6) overactivity may cause podocyte loss and progressive kidney function decline. TRPC6 inhibition may be a novel podocyte-targeted therapy as TRPC6 gain-of-function mutations cause autosomal dominantly inherited FSGS (genetic FSGS). Methods: Multicenter, Phase 2, double-blind, placebo-controlled, randomized (1:1:1:1) trial assessing efficacy and safety of an oral selective TRPC6 inhibitor (BI 764198) administered once daily (20 mg/40 mg/80 mg versus placebo) over 12 weeks in patients with primary FSGS or genetic FSGS due to known TRPC6 mutations. Patients were receiving stable conservative and immunosuppressive therapy with screening urinary protein:creatinine ratio (UPCR) of ≥1.0 g/g and estimated glomerular filtration rate of ≥30 mL/min/1.73 m2. The primary endpoint was the proportion of patients with a proteinuria response (≥25% UPCR reduction from baseline) at Week 12. Other key outcomes were safety, tolerability, and pharmacokinetics. Results: Sixty patients (7 with TRPC6 mutations) were treated and evaluable. Proteinuria responses at Week 12 were observed in 44.4% (8/18), 14.3% (2/14), and 42.9% (6/14) of patients receiving BI 764198 20 mg, 40 mg, and 80 mg, respectively, versus 7.1% (1/14) receiving placebo. In patients with TRPC6 mutations, 100% (4/4) receiving BI 764198 achieved a proteinuria response at Week 12 versus 0% (0/3) receiving placebo. The highest placebo-corrected mean change in UPCR at Week 12 was observed with the 20 mg dose: −39.82% (95% CI −56.17 to −17.36; p=0.002). BI 764198 was safe and well tolerated with no meaningful differences in adverse event frequencies across treatment arms. Conclusion: BI 764198 lowered proteinuria in FSGS and was well tolerated. This is the first evidence of efficacy with a podocyte-targeted therapy in FSGS. Funding: Commercial Support - The study was supported and funded by Boehringer Ingelheim. Medical writing support in the preparation of this abstract was provided by Laura George, PhD, CMPP of OPEN Health Communications, and funded by Boehringer Ingelheim, in accordance with Good Publication Practice (GPP) guidelines (www.ismpp.org/gpp-2022).
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- TRPC6 Inhibition for the Treatment of FSGS: Phase 2 Randomized Controlled Trial of BI 764198
- Date Crossref
- 01/10/2025
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
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University of Otago Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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University of Michigan Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Department of Medicine — University of Otago, Department of Pediatrics — University of Michigan et Michigan Medicine, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.