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

Hypertriglyceridemia Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-Controlled, Phase 2b Study of ISIS 678354 in Patients With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), and/or With Severe Hypertriglyceridemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05355402
• Other study ID #: ISIS 678354-CS8
• Status: Completed
• Phase: Phase 2
• Start date: May 9, 2022
• Est. completion date: December 21, 2023

Study information

• Verified date: May 2024
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: December 21, 2023
• Est. primary completion date: March 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases
• Hypertriglyceridemia
• Severe Hypertriglyceridemia

Intervention

Drug:
• Olezarsen
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.

Locations

Country	Name	City	State
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	Clinique des Maladies Lipidiques de Quebec Inc.	Quebec
Canada	Bluewater Clinical Research Group Inc	Sarnia	Ontario
United States	Excel Medical Clinical Trials, LLC	Boca Raton	Florida
United States	IACT Health	Columbus	Georgia
United States	West Broadway Clinic	Council Bluffs	Iowa
United States	Evanston Premier Healthcare Research	Evanston	Illinois
United States	Aa Mrc, Llc	Flint	Michigan
United States	Clinical Investigation Specialist	Gurnee	Illinois
United States	Green and Seidner Family Practice Associates	Lansdale	Pennsylvania
United States	Clinical Research of South Nevada	Las Vegas	Nevada
United States	Palm Research Center, Inc.	Las Vegas	Nevada
United States	Clinical Trials Research	Lincoln	California
United States	Main Street Physicians Care Waterway	Little River	South Carolina
United States	Louisville Metabolic and Atherosclerosis Research Center (L-MARC)	Louisville	Kentucky
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Southern Endocrinology Associates	Mesquite	Texas
United States	De La Cruz Research Center	Miami	Florida
United States	Catalina Research Institute, LLC	Montclair	California
United States	Suncoast Clinical Research, Inc.	New Port Richey	Florida
United States	York Clinical Research LLC	Norfolk	Virginia
United States	Health Concepts	Rapid City	South Dakota
United States	Tennessee Center for Clinical Trials	Tullahoma	Tennessee
United States	Research Physicians Network Alliance	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline at Month 6 (average of Weeks 25 and 27) in Fasting Triglycerides (TG)		Baseline and Month 6
Secondary	Percent Change From Baseline at Month 12 in Fasting TG		Baseline and Month 12
Secondary	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
Secondary	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
Secondary	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
Secondary	Proportion of Participants with Baseline TG = 500 mg/dL Who Achieve Fasting TG < 500 mg/dL at Month 12		Baseline and Month 12
Secondary	Percent Change From Baseline at Months 6 and 12 in Fasting apoC-III		Baseline, Months 6 and 12
Secondary	Percent Change From Baseline at Months 6 and 12 in Fasting VLDL-C		Baseline, Months 6 and 12
Secondary	Percent Change From Baseline at Months 6 and 12 in Fasting Remnant Cholesterol		Baseline, Months 6 and 12
Secondary	Percent Change From Baseline at Months 6 and 12 in Fasting Non-HDL-C		Baseline, Months 6 and 12
Secondary	Percent Change From Baseline at Months 6 and 12 in Fasting HDL-C		Baseline, Months 6 and 12
Secondary	Percent Change From Baseline at Months 6 and 12 in Fasting TC		Baseline, Months 6 and 12
Secondary	Percent Change From Baseline at Months 6 and 12 in Fasting apoB		Baseline, Months 6 and 12
Secondary	Percent Change From Baseline at Months 6 and 12 in Fasting LDL-C		Baseline, Months 6 and 12
Secondary	Percent Change From Baseline at Months 6 and 12 in apoA-1		Baseline, Months 6 and 12
Secondary	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
Secondary	Adjudicated acute pancreatitis event rate during the Treatment Period compared to placebo.		Baseline through Month 12