Safety, Tolerability, PK and PD Study of Inhaled ION-827359 - HV&CF
Research type
Research Study
Full title
A Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION-827359, an Antisense Oligonucleotide Inhibitor of ENaC, Administered to Healthy Volunteers and Patients with Cystic Fibrosis.
IRAS ID
252483
Contact name
David Bell
Contact email
Sponsor organisation
Ionis Pharmaceuticals Inc
Eudract number
2018-002621-27
Duration of Study in the UK
1 years, 7 months, 20 days
Research summary
Cystic Fibrosis (CF) is an autosomal recessive disease which results from mutations in the CF transmembrane conductance regulator (CFTR) gene. As a result ion-transport defects cause thick, viscous mucus. The production of mucus depends on the volume of the layer of fluid which lines the lung epithelium, termed the airway surface liquid (ASL). Restoring the ASL to a normal volume is a goal of CF therapy.
The hypothesis of using an epithelial sodium channel (ENaC) blocking molecule to restore ASL has been studied in pre-clinical and clinical studies.
The study drug in this study is ION-827359 is a 2.5-generation antisense oligonucleotide (ASO) drug targeted to reduce the ENaC protein. It has been studied in nonclinical studies in mouse models and the results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung.
This study will Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION-827359, an Antisense Oligonucleotide Inhibitor of ENaC, Administered to Healthy Volunteers.
REC name
HSC REC B
REC reference
18/NI/0145
Date of REC Opinion
14 Sep 2018
REC opinion
Favourable Opinion