Study of Plozasiran in Adults With Severe Hypertriglyceridemia at Risk of Acute Pancreatitis

Inclusion Criteria: * Males, or nonpregnant (who do not plan to become pregnant) nonlactating females * Established diagnosis of SHTG and prior documented evidence of fasting TG levels of ≥ 880 mg/dL (≥ 10 mmol/L) * Documented evidence of at least 1 prior AP event not attributed to other etiologies occurring within the last 60 months prior to Screening. * Fasting low-density lipoprotein cholesterol (LDL-C) ≤ 130 mg/dL (≤ 3.37 mmol/L) at Screening * Screening hemoglobin A1c (HbA1c) ≤ 9.5% * 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, or a treatment failure as determined by the Investigator) 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. * Use of any other hepatocyte targeted siRNA or antisense oligonucleotide molecule within 60 days or within 5 half-lives lives before day 1. Whichever is longer. * AP ≤ 4 weeks prior to Randomization/Day 1 * Body mass index (BMI) \> 45 kg/m\^2 * Any planned bariatric surgery or similar procedures to induce weight lost starting at consent through End of Study (EOS) * Planned coronary intervention (e.g. stent placement or heart bypass) during the study * History of arterial revascularization within 16 weeks of Screening * History of acute coronary syndrome event wit…