Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS APO(a)-LRx in Healthy Volunteers With Elevated Lipoprotein(a)

Summary

The purpose is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of IONIS APO(a)-LRx (ISIS 681257) given to healthy volunteer subjects.

Timeline

Start

2015-04

Primary completion

2016-02

Completion

2016-02

Outcome

Met primary endpoint

paper In the multidose groups, IONIS-APO(a)-LRx resulted in mean reductions in Lp(a) of 66% (SD 21·8) in the 10 mg group PMID 27665230 ↗

paper p=0·0007 for all vs placebo PMID 27665230 ↗

paper Both antisense oligonucleotides were safe. PMID 27665230 ↗

Publications

• Milosavljevic MN, Stefanovic SM, Pejcic AV. Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials. J Cardiovasc Pharmacol. 2023 Jul 1;82(1):1-12. doi: 10.1097/FJC.0000000000001429.
• Viney NJ, van Capelleveen JC, Geary RS, Xia S, Tami JA, Yu RZ, Marcovina SM, Hughes SG, Graham MJ, Crooke RM, Crooke ST, Witztum JL, Stroes ES, Tsimikas S. Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials. Lancet. 2016 Nov 5;388(10057):2239-2253. doi: 10.1016/S0140-6736(16)31009-1. Epub 2016 Sep 21.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Pelacarsen	Antisense oligonucleotide	10 mg	Subcutaneous
Subject	Pelacarsen	Antisense oligonucleotide	20 mg	Subcutaneous
Subject	Pelacarsen	Antisense oligonucleotide	40 mg	Subcutaneous
Subject	Pelacarsen	Antisense oligonucleotide	80 mg	Subcutaneous
Subject	Pelacarsen	Antisense oligonucleotide	120 mg	Subcutaneous

Indications