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

Status and phase: Completed; Phase 2

Conditions: Severe Hypertriglyceridemia; Atherosclerotic Cardiovascular Disease; Hypertriglyceridemia

Treatments: Drug: Placebo; Drug: Olezarsen

Study type: Interventional

Funder types: Industry

Identifiers

NCT05355402

ISIS 678354-CS8

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 154 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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154 participants in 2 patient groups, including a placebo group

Olezarsen

Experimental group

Description:

Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 49 weeks.

Treatment:

Drug: Olezarsen

Placebo

Placebo Comparator group

Description:

Olezarsen-matching placebo will be administered once every 4 weeks by SC injection for up to 49 weeks.

Treatment:

Drug: Placebo