Clinical trial NCT05355402: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertriglyceridemia
Atherosclerotic Cardiovascular Disease
Severe Hypertriglyceridemia
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-02
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent Change From Baseline at Month 6 (average of Weeks 25 and 27) in Fasting Triglycerides (TG)
timeFrame: Baseline and Month 6
Secondary outcomes:
measure: Percent Change From Baseline at Month 12 in Fasting TG
timeFrame: Baseline and Month 12
measure: 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
timeFrame: Baseline and Month 6
measure: 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
timeFrame: Baseline and Month 12
measure: Proportion of Participants with Baseline TG ≥ 500 mg/dL Who Achieve Fasting TG < 500 mg/dL (5.65 mmol/L) at Month 6
timeFrame: Baseline and Month 6
measure: Proportion of Participants with Baseline TG ≥ 500 mg/dL Who Achieve Fasting TG < 500 mg/dL at Month 12
timeFrame: Baseline and Month 12
measure: Percent Change From Baseline at Months 6 and 12 in Fasting apoC-III
timeFrame: Baseline, Months 6 and 12
measure: Percent Change From Baseline at Months 6 and 12 in Fasting VLDL-C
timeFrame: Baseline, Months 6 and 12
measure: Percent Change From Baseline at Months 6 and 12 in Fasting Remnant Cholesterol
timeFrame: Baseline, Months 6 and 12
measure: Percent Change From Baseline at Months 6 and 12 in Fasting Non-HDL-C
timeFrame: Baseline, Months 6 and 12
measure: Percent Change From Baseline at Months 6 and 12 in Fasting HDL-C
timeFrame: Baseline, Months 6 and 12
measure: Percent Change From Baseline at Months 6 and 12 in Fasting TC
timeFrame: Baseline, Months 6 and 12
measure: Percent Change From Baseline at Months 6 and 12 in Fasting apoB
timeFrame: Baseline, Months 6 and 12
measure: Percent Change From Baseline at Months 6 and 12 in Fasting LDL-C
timeFrame: Baseline, Months 6 and 12
measure: Percent Change From Baseline at Months 6 and 12 in apoA-1
timeFrame: Baseline, Months 6 and 12
measure: 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.
timeFrame: Baseline through Month 12
measure: Adjudicated acute pancreatitis event rate during the Treatment Period compared to placebo.
timeFrame: Baseline through Month 12
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials, LLC
state: Florida
city: Miami
country: United States
facility: De La Cruz Research Center
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc.
state: Florida
city: Winter Park
country: United States
facility: Research Physicians Network Alliance
state: Florida
city: Columbus
country: United States
facility: IACT Health
state: Georgia
city: Evanston
country: United States
facility: Evanston Premier Healthcare Research
state: Illinois
city: Gurnee
country: United States
facility: Clinical Investigation Specialist
state: Illinois
city: Council Bluffs
country: United States
facility: West Broadway Clinic
state: Iowa
city: Louisville
country: United States
facility: Louisville Metabolic and Atherosclerosis Research Center (L-MARC)
state: Kentucky
city: Flint
country: United States
facility: Aa Mrc, Llc
state: Michigan
city: Las Vegas
country: United States
facility: Clinical Research of South Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Palm Research Center, Inc.
state: Nevada
city: Lansdale
country: United States
facility: Green and Seidner Family Practice Associates
state: Pennsylvania
city: Little River
country: United States
facility: Main Street Physicians Care Waterway
state: South Carolina
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Tullahoma
country: United States
facility: Tennessee Center for Clinical Trials
state: Tennessee
city: Mesquite
country: United States
facility: Southern Endocrinology Associates
state: Texas
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Norfolk
country: United States
facility: York Clinical Research LLC
state: Virginia
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc
state: Ontario
city: Chicoutimi
country: Canada
facility: Ecogene-21
state: Quebec
city: Quebec
country: Canada
facility: Clinique des Maladies Lipidiques de Quebec Inc.
Study officials:
References:
citation: 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.