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

Phase 2

Completed

• Conditions: Hypertriglyceridemia; Atherosclerotic Cardiovascular Disease; Severe Hypertriglyceridemia
• Interventions: Drug: Olezarsen; Drug: Placebo

• Registration Number: NCT05355402
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

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).

Detailed 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.

Study Timeline

• Study First Submitted: 2022-04-26
• Study First Submitted QC: 2022-04-26
• Study First Posted: 2022-05-02
• Study Start: 2022-05-09
• Primary Completion: 2023-03-22
• Study Completion: 2023-12-21
• Disposition First Submitted: 2024-02-26
• Disposition First Posted: 2024-02-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-22
• Last Update Posted: 2024-11-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 154

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Olezarsen	Olezarsen	Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 49 weeks.
Placebo	Placebo	Olezarsen-matching placebo will be administered once every 4 weeks by SC injection for up to 49 weeks.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	Baseline and Month 12
Proportion of Participants with Baseline TG ≥ 500 mg/dL Who Achieve Fasting TG < 500 mg/dL at Month 12	Baseline and Month 12
Percent Change From Baseline at Months 6 and 12 in Fasting Non-HDL-C	Baseline, Months 6 and 12
Adjudicated acute pancreatitis event rate during the Treatment Period compared to placebo in patients with ≥ 2 events of adjudicated acute pancreatitis in 5 years prior to enrollment.	Baseline through 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	Baseline and Month 6
Percent Change From Baseline at Months 6 and 12 in Fasting LDL-C	Baseline, Months 6 and 12
Percent Change From Baseline at Months 6 and 12 in Fasting Remnant Cholesterol	Baseline, Months 6 and 12
Percent Change From Baseline at Months 6 and 12 in Fasting HDL-C	Baseline, Months 6 and 12
Percent Change From Baseline at Months 6 and 12 in Fasting TC	Baseline, Months 6 and 12
Percent Change From Baseline at Months 6 and 12 in apoA-1	Baseline, Months 6 and 12
Adjudicated acute pancreatitis event rate during the Treatment Period compared to placebo.	Baseline through Month 12
Percent Change From Baseline at Month 12 in Fasting TG	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	Baseline and Month 6
Percent Change From Baseline at Months 6 and 12 in Fasting VLDL-C	Baseline, Months 6 and 12
Percent Change From Baseline at Months 6 and 12 in Fasting apoB	Baseline, Months 6 and 12
Percent Change From Baseline at Months 6 and 12 in Fasting apoC-III	Baseline, Months 6 and 12

Trial Locations

Locations (24)

Main Street Physicians Care Waterway; 🇺🇸 Little River, South Carolina, United States

Ecogene-21; 🇨🇦 Chicoutimi, Quebec, Canada

Clinique des Maladies Lipidiques de Quebec Inc.; 🇨🇦 Quebec, Canada

Tennessee Center for Clinical Trials; 🇺🇸 Tullahoma, Tennessee, United States

Bluewater Clinical Research Group Inc; 🇨🇦 Sarnia, Ontario, Canada

Excel Medical Clinical Trials, LLC; 🇺🇸 Boca Raton, Florida, United States

De La Cruz Research Center; 🇺🇸 Miami, Florida, United States

Evanston Premier Healthcare Research; 🇺🇸 Evanston, Illinois, United States

Aa Mrc, Llc; 🇺🇸 Flint, Michigan, United States

Green and Seidner Family Practice Associates; 🇺🇸 Lansdale, Pennsylvania, United States

Palm Research Center, Inc.; 🇺🇸 Las Vegas, Nevada, United States

Clinical Trials Research; 🇺🇸 Lincoln, California, United States

Catalina Research Institute, LLC; 🇺🇸 Montclair, California, United States

IACT Health; 🇺🇸 Columbus, Georgia, United States

Clinical Investigation Specialist; 🇺🇸 Gurnee, Illinois, United States

West Broadway Clinic; 🇺🇸 Council Bluffs, Iowa, United States

York Clinical Research LLC; 🇺🇸 Norfolk, Virginia, United States

Southern Endocrinology Associates; 🇺🇸 Mesquite, Texas, United States

Louisville Metabolic and Atherosclerosis Research Center (L-MARC); 🇺🇸 Louisville, Kentucky, United States

Research Physicians Network Alliance; 🇺🇸 Winter Park, Florida, United States

Suncoast Clinical Research, Inc.; 🇺🇸 New Port Richey, Florida, United States

Clinical Research of South Nevada; 🇺🇸 Las Vegas, Nevada, United States

Health Concepts; 🇺🇸 Rapid City, South Dakota, United States

Manassas Clinical Research Center; 🇺🇸 Manassas, Virginia, United States