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

NCT05355402 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ISIS 678354-CS8
• Study Type: interventional
• Target: 154
• Locations: 2 countries
• Sites: 24

Brief Summary

The purpose of the study was to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo at Months 6 and 12 and the proportion of participants who achieve different thresholds in fasting TG. Other objectives were 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).

Conditions

Hypertriglyceridemia; Severe Hypertriglyceridemia; Atherosclerotic Cardiovascular Disease

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Fasting TG at Month 6

  Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the jump to reference (J2R) approach.

  Baseline, Month 6

Secondary Outcomes (25)

• Percent Change From Baseline in Fasting TG at Month 12

  Baseline, Month 12

• Percentage of Participants Who Achieved Fasting TG <150 mg/dL (1.69 Millimoles Per Liter [mmol/L]) at Month 6 With Baseline TG <500 mg/dL (5.65 mmol/L)

  Baseline, Month 6

• Percentage of Participants Who Achieved Fasting TG <150 mg/dL (1.69 mmol/L) at Month 12 With Baseline TG <500 mg/dL (5.65 mmol/L)

  Baseline, Month 12

• Percent Change From Baseline in Fasting Apolipoprotein C-III (ApoC-III) at Month 6

  Baseline, Month 6

• Percent Change From Baseline in Fasting ApoC-III at Month 12

  Baseline, Month 12

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants received olezarsen-matching placebo, as a single subcutaneous (SC) injection, once every 4 weeks for 53 weeks treatment period.

Drug: Placebo

Olezarsen 50 mg

EXPERIMENTAL

Participants received olezarsen 50 mg, as a single 0.5 milliliters (mL) SC injection, once every 4 weeks for 53 weeks treatment period.

Drug: Olezarsen

Olezarsen 80 mg

EXPERIMENTAL

Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Drug: Olezarsen

Interventions

Olezarsen DRUG

SC injection.

Also known as: ISIS 678354, AKCEA-APOCIII-LRx

Olezarsen 50 mg; Olezarsen 80 mg

Placebo DRUG

SC injection.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years at the time of informed consent
• Fall into at least 1 of the following groups (a or b):
• 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
• Severe hypertriglyceridemia with fasting TG ≥ 500 mg/dL (5.65 mmol/L).
• Participants must be on standard-of-care (SOC), lipid-lowering medications per local guidelines.
• Participants must be willing to comply with diet and lifestyle recommendations as able.

You may not qualify if:

• Diabetes with any of the following:
• Newly diagnosed within 12 weeks of screening
• Hemoglobin A1C (HbA1c) ≥ 9.5% at Screening
• Change in basal insulin regimen \> 20% within 3 months prior to Screening
• For participants with type 1 diabetes: episode of diabetic ketoacidosis, or ≥ 3 episodes of severe hypoglycemia within 6 months prior to Screening
• Acute coronary syndrome or stroke/transient ischemic attack (TIA) within 6 months prior to Screening
• 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
• Active pancreatitis within 4 weeks prior to Screening

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (24)

Clinical Trials Research

Lincoln, California, 95648, United States

Location

Catalina Research Institute, LLC

Montclair, California, 91763, United States

Location

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, 33434, United States

Location

De La Cruz Research Center

Miami, Florida, 33184, United States

Location

Suncoast Clinical Research, Inc.

New Port Richey, Florida, 34652, United States

Location

Research Physicians Network Alliance

Winter Park, Florida, 32792, United States

Location

IACT Health

Columbus, Georgia, 31904, United States

Location

Evanston Premier Healthcare Research

Evanston, Illinois, 60201, United States

Location

Clinical Investigation Specialist

Gurnee, Illinois, 60031, United States

Location

West Broadway Clinic

Council Bluffs, Iowa, 51501, United States

Location

Louisville Metabolic and Atherosclerosis Research Center (L-MARC)

Louisville, Kentucky, 40213, United States

Location

Aa Mrc, Llc

Flint, Michigan, 48504, United States

Location

Clinical Research of South Nevada

Las Vegas, Nevada, 89121, United States

Location

Palm Research Center, Inc.

Las Vegas, Nevada, 89148, United States

Location

Green and Seidner Family Practice Associates

Lansdale, Pennsylvania, 19446, United States

Location

Main Street Physicians Care Waterway

Little River, South Carolina, 29566, United States

Location

Health Concepts

Rapid City, South Dakota, 57702, United States

Location

Tennessee Center for Clinical Trials

Tullahoma, Tennessee, 37388, United States

Location

Southern Endocrinology Associates

Mesquite, Texas, 75149, United States

Location

Manassas Clinical Research Center

Manassas, Virginia, 20110, United States

Location

York Clinical Research LLC

Norfolk, Virginia, 23504, United States

Location

Bluewater Clinical Research Group Inc

Sarnia, Ontario, N7t 4X3, Canada

Location

Ecogene-21

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Clinique des Maladies Lipidiques de Quebec Inc.

Québec, G1V 4W2, Canada

Location

Related Publications (1)

• Bergmark BA, Marston NA, Prohaska TA, Alexander VJ, Zimerman A, Moura FA, Murphy SA, Goodrich EL, Zhang S, Gaudet D, Karwatowska-Prokopczuk E, Tsimikas S, Giugliano RP, Sabatine MS; Bridge-TIMI 73a Investigators. Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk. N Engl J Med. 2024 May 16;390(19):1770-1780. doi: 10.1056/NEJMoa2402309. Epub 2024 Apr 7.

  PMID: 38587249 DERIVED

MeSH Terms

Conditions

Hypertriglyceridemia; Atherosclerosis

Interventions

olezarsen

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Ionis Pharmaceuticals, Inc.
• Organization: Ionis Pharmaceuticals, Inc.

globalregulatoryaffairs@ionis.com

760-603-2346

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: May 2, 2022
• Study Start: May 9, 2022
• Primary Completion: March 22, 2023
• Study Completion: December 21, 2023
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); US (21)