Novel antisense inhibition of diacylglycerol O-acyltransferase 2 for treatment of non-alcoholic fatty liver disease: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial.
Aged
Body Mass Index
Canada
/ epidemiology
Case-Control Studies
Diabetes Mellitus, Type 2
/ blood
Diacylglycerol O-Acyltransferase
/ administration & dosage
Double-Blind Method
Drug Tolerance
Female
Humans
Hungary
/ epidemiology
Injections, Subcutaneous
Intra-Abdominal Fat
/ diagnostic imaging
Magnetic Resonance Imaging
/ methods
Male
Middle Aged
Non-alcoholic Fatty Liver Disease
/ complications
Oligonucleotides, Antisense
/ administration & dosage
Placebos
/ administration & dosage
Poland
/ epidemiology
Safety
Treatment Outcome
Journal
The lancet. Gastroenterology & hepatology
ISSN: 2468-1253
Titre abrégé: Lancet Gastroenterol Hepatol
Pays: Netherlands
ID NLM: 101690683
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
24
04
2020
revised:
29
04
2020
accepted:
01
05
2020
pubmed:
20
6
2020
medline:
15
9
2020
entrez:
20
6
2020
Statut:
ppublish
Résumé
Diacylglycerol-O-acyltransferase 2 (DGAT2) is one of two enzyme isoforms that catalyse the final step in the synthesis of triglycerides. IONIS-DGAT2 This double-blind, randomised, placebo-controlled, phase 2 study consisted of a 2-week screening period, a run-in period of up to 4 weeks, a 13-week treatment period of once-weekly dosing, and a 13-week post-treatment follow-up period. The study was done at 16 clinical research sites in Canada, Poland, and Hungary. Eligible participants were aged 18-75 years, had a body-mass index at screening between 27 kg/m Between Nov 3, 2017, and Nov 28, 2018, we screened 173 people for eligibility. 44 were enrolled and randomly assigned to receive either IONIS-DGAT2 Our results suggest that DGAT2 antisense inhibition could be a safe and efficacious strategy for treatment of NAFLD and support further investigation in patients with biopsy-proven NASH. Based on the pharmacological target, the response to treatment observed in this study population could extend to the broader population of patients with NAFLD. Ionis Pharmaceuticals.
Sections du résumé
BACKGROUND
Diacylglycerol-O-acyltransferase 2 (DGAT2) is one of two enzyme isoforms that catalyse the final step in the synthesis of triglycerides. IONIS-DGAT2
METHODS
This double-blind, randomised, placebo-controlled, phase 2 study consisted of a 2-week screening period, a run-in period of up to 4 weeks, a 13-week treatment period of once-weekly dosing, and a 13-week post-treatment follow-up period. The study was done at 16 clinical research sites in Canada, Poland, and Hungary. Eligible participants were aged 18-75 years, had a body-mass index at screening between 27 kg/m
FINDINGS
Between Nov 3, 2017, and Nov 28, 2018, we screened 173 people for eligibility. 44 were enrolled and randomly assigned to receive either IONIS-DGAT2
INTERPRETATION
Our results suggest that DGAT2 antisense inhibition could be a safe and efficacious strategy for treatment of NAFLD and support further investigation in patients with biopsy-proven NASH. Based on the pharmacological target, the response to treatment observed in this study population could extend to the broader population of patients with NAFLD.
FUNDING
Ionis Pharmaceuticals.
Identifiants
pubmed: 32553151
pii: S2468-1253(20)30186-2
doi: 10.1016/S2468-1253(20)30186-2
pii:
doi:
Substances chimiques
Oligonucleotides, Antisense
0
Placebos
0
DGAT2 protein, human
EC 2.3.1.20
Diacylglycerol O-Acyltransferase
EC 2.3.1.20
Banques de données
ClinicalTrials.gov
['NCT03334214']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
829-838Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK106419
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121378
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124318
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK120515
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.