The main objective of this study is to evaluate the effect of ION775 on fasting triglyceride (TG) levels in participants with hypertriglyceridemia (HTG) and severe hypertriglyceridemia (sHTG).

This is an open-label, parallel-dose study consisting of a 4-6 week screening period, a 6-month treatment period and a 6-month post-treatment follow-up period.

Key Inclusion Criteria:

1. Adult males and females with HTG (fasting TG more than or equal to (≥) 350 milligrams per deciliter (mg/dL) [3.95 millimoles per liter (mmol/L)] or with sHTG (fasting TG ≥ 500 mg/dL [5.65 mmol/L]).
2. Participants should be on standard of care lipid-lowering medications per local guidelines.

Key Exclusion Criteria:

1. Hemoglobin A1c (HbA1c) ≥ 8.5% at Screening.
2. Alanine aminotransferase or aspartate aminotransferase > 2.0 × upper limit of normal.
3. Total bilirubin > 1.5 upper limit of normal unless due to Gilbert's syndrome.
4. Estimated GFR < 30 mL/min/1.73 m^2.

Note: Other protocol pre-specified inclusion/exclusion criteria may apply.

Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.