Vascular Endothelial Growth Factor–B Blockade with CSL346 in Diabetic Kidney Disease
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Le résumé fourni par la source
Key Points The vascular endothelial growth factor B inhibitor CSL346 (8 or 16 mg/kg q4w) did not reduce urinary albumin-creatinine ratio at week 16 versus placebo in patients with type 2 diabetes mellitus and diabetic kidney disease. CSL346 was generally well tolerated at both doses; however, CSL346 (16 mg/kg) significantly increased diastolic BP versus placebo. Background Increased vascular endothelial growth factor B (VEGF-B) expression in patients with diabetic kidney disease (DKD) is associated with increased lipid deposition in glomerular podocytes. Reducing VEGF-B activity in animal models of DKD using an anti–VEGF-B antibody improved histological evidence of glomerular injury and reduced albuminuria, effects attributed to prevention of ectopic lipid deposition in the kidney. CSL346 is a novel humanized monoclonal antibody that binds VEGF-B with high affinity. Targeting VEGF-B in patients with type 2 diabetes mellitus may improve DKD progression markers. Methods An international, randomized, double-blind, placebo-controlled, phase 2a study (NCT04419467) assessed CSL346 (8 or 16 mg/kg subcutaneously every 4 weeks for 12 weeks) in participants with type 2 diabetes mellitus and a urinary albumin-creatinine ratio (UACR) ≥150 mg/g (17.0 mg/mmol), and eGFR >20 ml/min per 1.73 m 2 . Efficacy, safety/tolerability, pharmacokinetics, and pharmacodynamics of CSL346 were evaluated. The primary analysis compared the change from baseline in log-transformed UACR between the two CSL346 dose groups combined versus placebo at week 16. Results In total, 114 participants were randomized. CSL346 did not significantly reduce UACR compared with placebo at week 16 (combined CSL346 group difference from placebo [95% confidence interval], 4.0% [−14.7 to 26.8]). Furthermore, no effect was seen in participant subgroups (degree of kidney impairment or sodium-glucose cotransporter 2 inhibitor use) or on urinary biomarkers reflecting proximal tubular injury. CSL346 was generally well tolerated; however, diastolic BP was significantly higher with CSL346 16 mg/kg versus placebo from week 2 onward, with differences ranging from +3.8 to +5.3 mm Hg ( P = 0.002 at week 16). Conclusions CSL346 did not reduce UACR compared with placebo at 16 weeks in participants with type 2 diabetes mellitus and DKD and was associated with an increase in diastolic BP. Clinical Trial registry name and registration number: VEGF-B Blockade with the Monoclonal Antibody CSL346 in Subjects with DKD, NCT04419467.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Vascular Endothelial Growth Factor–B Blockade with CSL346 in Diabetic Kidney Disease
- Date Crossref
- 16/08/2024
- 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.
Où se fait cette recherche
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CSL (United States) pays non établi dans la noticeEntreprise
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University of Toronto Division of Nephrology pays non établi dans la noticeUniversité ou école supérieure
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University of Utah Division of Biostatistics pays non établi dans la noticeUniversité ou école supérieure
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University Medical Center Groningen Department of Clinical Pharmacy and Pharmacology pays non établi dans la noticeÉtablissement de santé
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University of Groningen Department of Clinical Pharmacy & Pharmacology pays non établi dans la noticeUniversité ou école supérieure
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The George Institute for Global Health pays non établi dans la noticeStructure de recherche
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The University of Sydney NHMRC Clinical Trials Centre pays non établi dans la noticeUniversité ou école supérieure
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Concord Repatriation General Hospital Department of Renal Medicine pays non établi dans la noticeÉtablissement de santé
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National Health and Medical Research Council pays non établi dans la noticeOrganisme public
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Vanderbilt University Medical Center Division of Nephrology pays non établi dans la noticeÉtablissement de santé
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CSL (Australia) pays non établi dans la noticeEntreprise
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CSL Behring LLC pays non établi dans la noticeInstitution
CSL (United States), Division of Nephrology — University of Toronto et Division of Biostatistics — University of Utah, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.