Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis

• Verfasst von: Sermet-Gaudelus, Isabelle [VerfasserIn]
• Verfasst von: Clancy, John P. [VerfasserIn]
• Verfasst von: Nichols, David P. [VerfasserIn]
• Verfasst von: Nick, Jerry A. [VerfasserIn]
• Verfasst von: De Boeck, Kris [VerfasserIn]
• Verfasst von: Solomon, George M. [VerfasserIn]
• Verfasst von: Mall, Marcus A. [VerfasserIn]
• Verfasst von: Bolognese, James [VerfasserIn]
• Verfasst von: Bouisset, Florilene [VerfasserIn]
• Verfasst von: den Hollander, Wilhelmina [VerfasserIn]
• Verfasst von: Paquette-Lamontagne, Nicolas [VerfasserIn]
• Verfasst von: Tomkinson, Nigel [VerfasserIn]
• Verfasst von: Henig, Noreen [VerfasserIn]
• Verfasst von: Elborn, J. Stuart [VerfasserIn]
• Verfasst von: Rowe, Steven M. [VerfasserIn]
• Titel: Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis
• Verf.angabe: Isabelle Sermet-Gaudelus, John P. Clancy, David P. Nichols, Jerry A. Nick, Kris De Boeck, George M. Solomon, Marcus A. Mall, James Bolognese, Florilene Bouisset, Wilhelmina den Hollander, Nicolas Paquette-Lamontagne, Nigel Tomkinson, Noreen Henig, J. Stuart Elborn, Steven M. Rowe
• Jahr: 2019
• Jahr des Originals: 2018
• Umfang: 7 S.
• Fussnoten: Available online 19 November 2018 ; Gesehen am 30.09.2019
• Titel Quelle: Enthalten in: Journal of cystic fibrosis
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 2002
• Jahr Quelle: 2019
• Band/Heft Quelle: 18(2019), 4, Seite 536-542
• ISSN Quelle: 1873-5010
• DOI: doi:10.1016/j.jcf.2018.10.015
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Antisense Oligonucleotide
• Sach-SW: Clinical Trial
• Sach-SW: Cystic Fibrosis Transmembrane Conductance Regulator delta F508
• Sach-SW: Nasal Potential Difference
• Sach-SW: Pulmonary Medicine
• K10plus-PPN: 1677941375

Abstract

Background - Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In this study we assessed the effect of antisense oligonucleotide eluforsen on CFTR biological activity measured by Nasal Potential Difference (NPD) in patients with the most common mutation, F508del-CFTR. - Methods - This multi-centre, exploratory, open-label study recruited adults with CF homozygous or compound heterozygous for the F508del-CFTR mutation. Subjects received intranasal eluforsen three times weekly for 4weeks. The primary endpoint was the within-subject change from baseline in total chloride transport (Cl-free+iso), as assessed by NPD. Secondary endpoints included within-subject change from baseline in sodium transport. - Results - In the homozygous cohort (n=7; per-protocol population), mean change (90% confidence interval) in Cl-free+iso was −3.0mV (−6.6; 0.6) at day 15, −4.1mV (−7.8; −0.4, p=.04) at day 26 (end of treatment) and−3.7mV (−8.0; 0.6) at day 47. This was supported by improved sodium transport as assessed by an increase in average basal potential difference at day 26 of +9.4mV (1.1; 17.7, p=.04). The compound heterozygous cohort (n=7) did not show improved chloride or sodium transport NPD values. Eluforsen was well tolerated with a favourable safety profile. - Conclusions - In F508del-CFTR homozygous subjects, repeated intranasal administration of eluforsen improved CFTR activity as measured by NPD, an encouraging indicator of biological activity.