A Study to Assess the Safety, Efficacy, and Pharmacokinetics of Multiple Doses of ION224

Summary

The purpose of this study is to assess the effect of multiple ION224 doses when administered by subcutaneous (SC) injection for 49 weeks (end of the treatment \[EOT\]) on non-alcoholic steatohepatitis (NASH) histologic improvement and to assess the effect on liver steatosis by magnetic resonance imaging-determined proton density fat fraction (MRI-PDFF), additional changes in NASH histologic features, liver biochemistry tests, and plasma lipid profile.

Timeline

Start

2021-06-17

Primary completion

2024-01-10

Completion

2024-02-28

Outcome

Met primary endpoint

paper The primary endpoint was met in 18 (46%) of 39 participants in the 90-mg group PMID 40849139 ↗

paper 20 (59%) of 34 in the 120-mg group (58·8% [42·3-75·4]; 40·1% [18·7- 61·4], p=0·0002) compared with six (19%) of 32 in the placebo group PMID 40849139 ↗

release “The study met its primary endpoint at both doses (120 mg and 90 mg), achieving liver histologic improvement” ionis.com ↗

Publications

• Loomba R, Morgan E, Yousefi K, Li D, Geary R, Bhanot S, Alkhouri N; ION224-CS2 Investigators. Antisense oligonucleotide DGAT-2 inhibitor, ION224, for metabolic dysfunction-associated steatohepatitis (ION224-CS2): results of a 51-week, multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2025 Aug 23;406(10505):821-831. doi: 10.1016/S0140-6736(25)00979-1.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	ION224	Antisense oligonucleotide	60 mg	Subcutaneous
Subject	ION224	Antisense oligonucleotide	90 mg	Subcutaneous
Subject	ION224	Antisense oligonucleotide	120 mg	Subcutaneous

Indications