A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia

Ionis Pharmaceuticals

Status and phase: Active, not recruiting; Phase 3

Conditions: Hypertriglyceridemia; Cardiovascular Diseases; Atherosclerosis

Treatments: Drug: Placebo; Drug: Olezarsen

Study type: Interventional

Funder types: Industry

Identifiers

NCT05610280

2022-501486-53 (EudraCT Number)

ISIS 678354-CS9

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,478 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

1,478 participants in 2 patient groups, including a placebo group

Olezarsen

Experimental group

Description:

Participants will be randomized to receive multiple doses of olezarsen, once every 4 weeks by subcutaneous (SC) injection up to Week 49.

Treatment:

Drug: Olezarsen

Placebo

Placebo Comparator group

Description:

Participants will be randomized to receive olezarsen-matching placebo, once every 4 weeks by SC injection up to Week 49.

Treatment:

Drug: Placebo