A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Adults With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), and/or With Severe Hypertriglyceridemia

Ionis Pharmaceuticals, Inc.154 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 at Months 6 and 12 and the percentage of participants who achieve different thresholds in fasting TG. Another objective is to evaluate the effect of olezarsen on percent change in fasting apolipoprotein C-III (apoC-III), very low-density lipoprotein cholesterol (VLDL-C), remnant cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, total cholesterol (TC), apolipoprotein B (apoB), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A-1 (apoA-1).

This will be a multi-center, randomized, double-blind, placebo-controlled study in approximately 152 participants with hypertriglyceridemia (triglycerides \> 150 milligrams per deciliter \[mg/dL\]) and established or at increased risk for atherosclerotic cardiovascular disease, and/or with severe hypertriglyceridemia. The study will have an up to 8-week screening period, a 53-week treatment period, and a 13-week post-treatment follow-up period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

154

Conditions

Hypertriglyceridemia Atherosclerotic Cardiovascular Disease

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Aged ≥ 18 years at the time of informed consent 2. Fall into at least 1 of the following groups (a or b): 1. Hypertriglyceridemia with fasting TG ≥ 150 mg/dL (1.69 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 2. Severe hypertriglyceridemia with fasting TG ≥ 500 mg/dL (5.65 mmol/L). 3. Participants must be on standard-of-care (SOC), lipid-lowering medications per local guidelines. 4. Participants must be willing to comply with diet and lifestyle recommendations as able. Exclusion Criteria: 1. Diabetes with any of the following: 1. Newly diagnosed within 12 weeks of screening 2. Hemoglobin A1C (HbA1c) ≥ 9.5% at Screening 3. Change in basal insulin regimen \> 20% within 3 months prior to Screening 4. For participants with type 1 diabetes: episode of diabetic ketoacidosis, or ≥ 3 episodes of severe hypoglycemia within 6 months prior to Screening 2. Acute coronary syndrome or stroke/transient ischemic attack (TIA) within 6 months prior to Screening 3. Major surgery, peripheral revascularization, or non-urgent percutaneous coronary intervention (PCI) within 3 months prior to Screening, or upcoming planned major surgery or major procedure (e.g., arterial revascularization) during the course of the study 4. Active pancreatitis within 4 weeks prior to Screening

Locations (24)

Clinical Trials Research

Lincoln, California, United States

Catalina Research Institute, LLC

Montclair, California, United States

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, United States

De La Cruz Research Center

Miami, Florida, United States

Suncoast Clinical Research, Inc.

New Port Richey, Florida, United States

Research Physicians Network Alliance

Winter Park, Florida, United States

IACT Health

Columbus, Georgia, United States

Evanston Premier Healthcare Research

Evanston, Illinois, United States

Clinical Investigation Specialist

Gurnee, Illinois, United States

West Broadway Clinic

Council Bluffs, Iowa, United States

...and 14 more locations

Outcomes

Primary Outcomes

Percent Change From Baseline at Month 6 (average of Weeks 25 and 27) in Fasting Triglycerides (TG)

Time frame: Baseline and Month 6

Secondary Outcomes

Percent Change From Baseline at Month 12 in Fasting TG

Time frame: Baseline and Month 12

Proportion of Participants with Baseline TG < 500 mg/dL (5.65 mmol/L) Who Achieve Fasting TG < 150 milligrams per deciliter (mg/dL) (1.69 millimoles per liter [mmol/L]) at Month 6

Time frame: Baseline and Month 6

Proportion of Participants with Baseline TG < 500 mg/dL (5.65 mmol/L) Who Achieve Fasting TG < 150 mg/dL (1.69 mmol/L) at Month 12

Time frame: Baseline and Month 12

Proportion of Participants with Baseline TG ≥ 500 mg/dL Who Achieve Fasting TG < 500 mg/dL (5.65 mmol/L) at Month 6

Time frame: Baseline and Month 6

Proportion of Participants with Baseline TG ≥ 500 mg/dL Who Achieve Fasting TG < 500 mg/dL at Month 12

Time frame: Baseline and Month 12

Percent Change From Baseline at Months 6 and 12 in Fasting apoC-III