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Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Antisense oligonucleotide eluforsen is safe and improves respiratory symptoms in F508DEL cystic fibrosis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. The impact of chest computed tomography and chest radiography on clinical management of cystic fibrosis lung disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Markers of bone turnover are reduced in patients with CF related diabetes; the role of glucose

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Optimization of colistin dosing regimen for cystic fibrosis patients with chronic Pseudomonas aeruginosa biofilm lung infections

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  • Pavel Drevinek
  • Tacjana Pressler
  • Marco Cipolli
  • Kris De Boeck
  • Carsten Schwarz
  • Florilene Bouisset
  • Marie Boff
  • Noreen Henig
  • Nicolas Paquette-Lamontagne
  • Sonya Montgomery
  • Jaakko Perquin
  • Nigel Tomkinson
  • Wilhelmina den Hollander
  • J Stuart Elborn
Vis graf over relationer

BACKGROUND: Eluforsen is an antisense oligonucleotide designed to bind to the mRNA region around the F508-encoding deletion and restore the cystic fibrosis transmembrane conductance regulator (CFTR) protein function in the airway epithelium. We assessed the safety and tolerability, pharmacokinetics and exploratory measures of efficacy of inhaled eluforsen in cystic fibrosis (CF) patients homozygous for the F508del-CFTR mutation.

METHODS: This randomised, double-blind, placebo-controlled, dose escalation 1b study recruited adult CF subjects with a FEV1 > 70% predicted in four single ascending dose cohorts and four multiple ascending dose cohorts. Primary objectives were safety and tolerability. Secondary endpoints included pharmacokinetics, percent predicted forced expiratory volume in 1 s (ppFEV1), and Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Symptom Score (RSS).

RESULTS: Single and multiple doses of inhaled eluforsen up to 50 mg were safe and well tolerated. A maximum tolerated dose was not established. Systemic exposure was low in all cohorts and lung function remained stable throughout the study. Three of four eluforsen-treated groups in the MAD study demonstrated an improvement in CFQ-R RSS at end of treatment with adjusted mean change from baseline values ranging from 6.4 to 12.7 points. In comparison, there was a mean decrease of 6.5 points in the placebo group from baseline to end of treatment.

CONCLUSIONS: Inhaled eluforsen up to 50 mg dosed 3 times per week for 4 weeks was safe and well tolerated, showed low systemic exposure, and demonstrated improvement in CFQ-R RSS, a relevant measure of clinical benefit in CF patients.

OriginalsprogEngelsk
TidsskriftJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
Vol/bind19
Udgave nummer1
Sider (fra-til)99-107
Antal sider9
ISSN1569-1993
DOI
StatusUdgivet - jan. 2020

ID: 59079776