Atherosclerosis, Cardiovascular Diseases, Hypertriglyceridemia
Conditions
Keywords
ISIS 678354, Olezarsen
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 in participants with hypertriglyceridemia and atherosclerotic cardiovascular disease, or with severe hypertriglyceridemia.
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.
Interventions
DRUGOlezarsen
Olezarsen will be administered by SC injection.
DRUGPlacebo
Olezarsen-matching placebo will be administered by SC injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline to Week 25 in Fasting Triglycerides (TG) Compared to Placebo | Baseline to Week 25 |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline to Week 53 in Fasting TG Compared to Placebo | Baseline to Week 53 |
| Proportion of Participants who Achieve Fasting TG <150 Milligrams per Deciliter (mg/dL) at Weeks 25 and 53 Compared to Placebo | Baseline, Weeks 25 and 53 |
| Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein C-III (apoC-III) Compared to Placebo | Baseline to Weeks 25 and 53 |
| Percent Change From Baseline to Weeks 25 and 53 in Fasting Very Low-Density Lipoprotein-Cholesterol (VLDL)-C Compared to Placebo | Baseline to Weeks 25 and 53 |
| Percent Change From Baseline to Weeks 25 and 53 in Fasting Remnant Cholesterol Compared to Placebo | Baseline to Weeks 25 and 53 |
| Percent Change From Baseline to Weeks 25 and 53 in Fasting non-High Density Lipoprotein-Cholesterol (HDL)-C Compared to Placebo | Baseline to Weeks 25 and 53 |
| Percent Change From Baseline to Weeks 25 and 53 in Fasting High-Density Lipoprotein-Cholesterol (HDL)-C Compared to Placebo | Baseline to Weeks 25 and 53 |
| Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein B (apoB) Compared to Placebo | Baseline to Weeks 25 and 53 |
| Percent Change From Baseline to Weeks 25 and 53 in Fasting Low-Density Lipoprotein-Cholesterol (LDL)-C Compared to Placebo | Baseline to Weeks 25 and 53 |
Countries
Bulgaria, Canada, Czechia, Denmark, France, Hungary, Italy, Netherlands, Norway, Poland, Portugal, Slovakia, Spain, United States
Outcome results
None listed