This study will be a Phase 2, double-blind, randomized, placebo-controlled study in up to 72 participants. Participants will be randomized in a 2:1 ratio to either IONIS-AGT-LRX or matching placebo and receive a once-weekly SC treatment. The length of participation in the study will be approximately 35 weeks, which includes an up to 10-week screening period, a 12-week treatment period, and a 13-week post-treatment period.
The purpose of this study is to evaluate the effect of IONIS-AGT-LRX weekly subcutaneous (SC) injection on plasma angiotensinogen (AGT) concentration from Baseline to Study Day 85 (Week 13) and to evaluate the effect of IONIS-AGT-LRx weekly SC injection on plasma AGT concentration and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels at each scheduled visit in chronic heart failure participants with reduced ejection fraction (HFrEF).