Phase 3 Study of Plozasiran in Adults With Hypertriglyceridemia

This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with hypertriglyceridemia (HTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo and be evaluated for efficacy and safety.

Inclusion Criteria: * Males, or nonpregnant (who do not plan to become pregnant) nonlactating females, who are ≥18 years of age at screening * Established diagnosis of hypertriglyceridemia (HTG) and prior documented evidence (medical history) of mean fasting TG level ≥150 mg/dL (≥1.69 mm/L) and ≤499 mg/dL (≤5.64 mmol/L) * Mean fasting TG level ≥150 mg/dL (≥1.69 mmol/L) and ≤499 mg/dL (≤5.64 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period * Fasting low density lipoprotein-cholesterol (LDL-C) ≤ 130 mg/dL (≤3.37 mmol/L) at screening * Screening HbA1c ≤9.0% * Willing to follow diet counseling and maintain a stable low-fat diet * Must be on standard of care lipid and TG-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator, including an inability to safely administer or re-administer a specific drug because of fear, preference, genetic, clinical, or metabolic considerations, or due a previous adverse reaction associated with, attributed to, or caused by specific drug) prior to collection of qualifying TG levels. Exclusion Criteria: * Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) that targets lipids and/or triglycerides within 365 days before Day 1 (except inclisiran, which is permitted). Administration of investigational drug and inclisiran must be separated by at least 4 weeks. * Use of any other hepatocyte targeted siRNA or antisense Oligonucleotide molecule within 60 days or within 5-half-lives before Day 1 based on plasma pharmacokinetics (PK), whichever is longer * Acute pancreatitis within 4 weeks prior to screening * Body mass index \>45 kg/m\^2 Note: Additional Inclusion/Exclusion criteria may apply per protocol