A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia
Purpose
The purpose of the study is to evaluate the effect of olezarsen on percent change in fasting triglyceride (TG) levels compared to placebo in participants with hypertriglyceridemia and atherosclerotic cardiovascular disease, or with severe hypertriglyceridemia.
Conditions
- Hypertriglyceridemia
- Cardiovascular Diseases
- Atherosclerosis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Participants must fall into 1 of the following groups (a or b): a. Hypertriglyceridemia with fasting TG ≥200 mg/dL (2.26 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 b. Severe hypertriglyceridemia with fasting TG ≥500 mg/dL (5.65 mmol/L) - Participants should be on standard of care (SOC) lipid-lowering medications per local guidelines. Lipid-lowering medications should be optimized and stabilized for at least 4 weeks prior to Screening to minimize changes in these medications during the study.
Exclusion Criteria
- Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening - Alanine aminotransferase or aspartate aminotransferase > 3.0 × upper limit of normal - Total bilirubin > 1.5 upper limit of normal unless due to Gilbert's syndrome - Estimated GFR < 30 mL/min/1.73 m^2 NOTE: Other Inclusion/Exclusion criteria may apply.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Olezarsen |
Participants will be randomized to receive multiple doses of olezarsen, once every 4 weeks by subcutaneous (SC) injection up to Week 49. |
|
|
Placebo Comparator Placebo |
Participants will be randomized to receive olezarsen-matching placebo, once every 4 weeks by SC injection up to Week 49. |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- Ionis Pharmaceuticals, Inc.
Study Contact
Detailed Description
This is a Phase 3, multi-center, placebo-controlled study in approximately 1475 participants with hypertriglyceridemia and atherosclerotic cardiovascular disease. The study consists of 3 periods: 1) Screening Period: Week -12 to Week -1 (up to 12 weeks); 2) Treatment Period up to Week 53; and 3) Post-Treatment Follow-up Period: Week 54 to Week 66 (13 weeks). Participants enrolled will receive olezarsen or placebo once every 4 weeks during the 53-week Treatment Period. The Screening Period was extended with no impact to overall study timelines. A coronary computed tomographic angiography (CTA) sub study will be performed to assess whether triglyceride lowering through inhibition of apoC-III protein synthesis may reduce coronary plaque progression.