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

NCT ID: NCT05355402

Last Updated: 2024-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

154 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-09

Study Completion Date

2023-12-21

Brief Summary

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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

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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.

Conditions

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Hypertriglyceridemia Atherosclerotic Cardiovascular Disease Severe Hypertriglyceridemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Olezarsen

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

Group Type EXPERIMENTAL

Olezarsen

Intervention Type DRUG

Olezarsen will be administered by SC injection.

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Olezarsen

Olezarsen will be administered by SC injection.

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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ISIS 678354 AKCEA-APOCIII-LRx

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Clinical Trials Research

Lincoln, California, United States

Site Status

Catalina Research Institute, LLC

Montclair, California, United States

Site Status

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, United States

Site Status

De La Cruz Research Center

Miami, Florida, United States

Site Status

Suncoast Clinical Research, Inc.

New Port Richey, Florida, United States

Site Status

Research Physicians Network Alliance

Winter Park, Florida, United States

Site Status

IACT Health

Columbus, Georgia, United States

Site Status

Evanston Premier Healthcare Research

Evanston, Illinois, United States

Site Status

Clinical Investigation Specialist

Gurnee, Illinois, United States

Site Status

West Broadway Clinic

Council Bluffs, Iowa, United States

Site Status

Louisville Metabolic and Atherosclerosis Research Center (L-MARC)

Louisville, Kentucky, United States

Site Status

Aa Mrc, Llc

Flint, Michigan, United States

Site Status

Clinical Research of South Nevada

Las Vegas, Nevada, United States

Site Status

Palm Research Center, Inc.

Las Vegas, Nevada, United States

Site Status

Green and Seidner Family Practice Associates

Lansdale, Pennsylvania, United States

Site Status

Main Street Physicians Care Waterway

Little River, South Carolina, United States

Site Status

Health Concepts

Rapid City, South Dakota, United States

Site Status

Tennessee Center for Clinical Trials

Tullahoma, Tennessee, United States

Site Status

Southern Endocrinology Associates

Mesquite, Texas, United States

Site Status

Manassas Clinical Research Center

Manassas, Virginia, United States

Site Status

York Clinical Research LLC

Norfolk, Virginia, United States

Site Status

Bluewater Clinical Research Group Inc

Sarnia, Ontario, Canada

Site Status

Ecogene-21

Chicoutimi, Quebec, Canada

Site Status

Clinique des Maladies Lipidiques de Quebec Inc.

Québec, , Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 38587249 (View on PubMed)

Other Identifiers

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ISIS 678354-CS8

Identifier Type: -

Identifier Source: org_study_id