Study of ISIS 678354 (AKCEA-APOCIII-LRx) in Participants With Hypertriglyceridemia and Established Cardiovascular Disease (CVD)

Summary

This was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, including tolerability, of ISIS 678354 and to assess the efficacy of different doses and dosing regimens of ISIS 678354 for reduction of serum triglyceride (TG) levels in participants with hypertriglyceridemia and established CVD or at a high risk for CVD.

Timeline

Start

2018-01-30

Primary completion

2019-11-25

Completion

2020-02-25

Outcome

Met primary endpoint

registry analysis (superiority test); Pooled Placebo vs Cohort A: ISIS 678354: 10 mg Q4W; p = 0.0042; Mean Difference in % CFB -27 (95% CI -41 to -10); ANCOVA NCT03385239 ↗

registry analysis (superiority test); Pooled Placebo vs Cohort C: ISIS 678354: 15 mg Q2W; p <0.0001; Mean Difference in % CFB -58 (95% CI -66 to -48); ANCOVA NCT03385239 ↗

registry analysis (superiority test); Pooled Placebo vs Cohort D: ISIS 678354: 10 mg QW; p <0.0001; Mean Difference in % CFB -63 (95% CI -70 to -54); ANCOVA NCT03385239 ↗

registry analysis (superiority test); Pooled Placebo vs Cohort B: ISIS 678354: 50 mg Q4W; p <0.0001; Mean Difference in % CFB -62 (95% CI -69 to -53); ANCOVA NCT03385239 ↗

Publications

• Tardif JC, Karwatowska-Prokopczuk E, Amour ES, Ballantyne CM, Shapiro MD, Moriarty PM, Baum SJ, Hurh E, Bartlett VJ, Kingsbury J, Figueroa AL, Alexander VJ, Tami J, Witztum JL, Geary RS, O'Dea LSL, Tsimikas S, Gaudet D. Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. Eur Heart J. 2022 Apr 6;43(14):1401-1412. doi: 10.1093/eurheartj/ehab820.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Olezarsen	Antisense oligonucleotide	10 mg	Subcutaneous
Subject	Olezarsen	Antisense oligonucleotide	15 mg	Subcutaneous
Subject	Olezarsen	Antisense oligonucleotide	50 mg	Subcutaneous

Indications