A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia

Ionis Pharmaceuticals, Inc.1,478 enrolled

Overview

The purpose of the study is to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo in participants with hypertriglyceridemia and atherosclerotic cardiovascular disease, or with severe hypertriglyceridemia.

This is a Phase 3, multi-center, placebo-controlled study in approximately 1475 participants with hypertriglyceridemia and atherosclerotic cardiovascular disease. The study consists of 3 periods: 1) Screening Period: Week -12 to Week -1 (up to 12 weeks); 2) Treatment Period up to Week 53; and 3) Post-Treatment Follow-up Period: Week 54 to Week 66 (13 weeks). Participants enrolled will receive olezarsen or placebo once every 4 weeks during the 53-week Treatment Period. The Screening Period was extended with no impact to overall study timelines. A coronary computed tomographic angiography (CTA) sub study will be performed to assess whether triglyceride lowering through inhibition of apoC-III protein synthesis may reduce coronary plaque progression.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

1,478

Conditions

Hypertriglyceridemia Cardiovascular Diseases Atherosclerosis

Interventions

OlezarsenDRUG

Olezarsen will be administered by SC injection.

PlaceboDRUG

Olezarsen-matching placebo will be administered by SC injection.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants must fall into 1 of the following groups (a or b): a. Hypertriglyceridemia with fasting TG ≥200 mg/dL (2.26 millimoles per liter \[mmol/L\]) and \<500 mg/dL (5.65 mmol/L) with either * Clinical diagnosis of atherosclerotic cardiovascular disease (ASCVD) or * At increased risk for ASCVD b. Severe hypertriglyceridemia with fasting TG ≥500 mg/dL (5.65 mmol/L) * Participants should be on standard of care (SOC) lipid-lowering medications per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study. Exclusion Criteria: * Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening * Alanine aminotransferase or aspartate aminotransferase \> 3.0 × upper limit of normal * Total bilirubin \> 1.5 upper limit of normal unless due to Gilbert's syndrome * Estimated GFR \< 30 mL/min/1.73 m\^2 NOTE: Other Inclusion/Exclusion criteria may apply.

Locations (168)

Outcomes

Primary Outcomes

Percent Change From Baseline to Week 25 in Fasting Triglycerides (TG) Compared to Placebo

Time frame: Baseline to Week 25

Secondary Outcomes

Percent Change From Baseline to Week 53 in Fasting TG Compared to Placebo

Time frame: Baseline to Week 53

Proportion of Participants who Achieve Fasting TG <150 Milligrams per Deciliter (mg/dL) at Weeks 25 and 53 Compared to Placebo

Time frame: Baseline, Weeks 25 and 53

Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein C-III (apoC-III) Compared to Placebo