A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a Phase 3, multi-center, placebo-controlled study of up to 1312 participants with hypertriglyceridemia and atherosclerotic cardiovascular disease. The study consists of 3 periods: 1) Screening Period: Week -8 to Week -1 (up to 8 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Olezarsen Participants will be randomized to receive multiple doses of olezarsen, once every 4 weeks by subcutaneous (SC) injection for up to Week 49. |
Drug: Olezarsen
Olezarsen will be administered by SC injection.
Other Names:
|
| Placebo Comparator: Placebo Participants will be randomized to receive olezarsen-matching placebo, once every 4 weeks by SC injection for up to Week 49. |
Drug: Placebo
Olezarsen-matching placebo will be administered by SC injection.
|
Outcome Measures
Primary Outcome Measures
- Percent Change From Baseline to Week 25 in Fasting Triglycerides (TG) Compared to Placebo [Baseline to Week 25]
Secondary Outcome Measures
- 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 in the Subgroup of Participants with Baseline TG <500 mg/dL [Baseline, Weeks 25 and 53]
- Proportion of Participants who Achieve Fasting TG <500 mg/dL at Weeks 25 and 53 Compared to Placebo in the Subgroup of Participants with Baseline TG ≥500 mg/dL [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 Total Cholesterol (TC) 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 Apolipoprotein B-48 (apoB-48) 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]
- Percent Change From Baseline to Weeks 25 and 53 in Fasting Apolipoprotein A-1 (apoA-1) Compared to Placebo [Baseline to Weeks 25 and 53]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Participants must fall into 1 of the following groups (a or b):
- 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 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 > 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Alabama Clinical Therapeutics, LLC Alabaster | Birmingham | Alabama | United States | 35235 |
| 2 | Clinical Trials Research | Lincoln | California | United States | 95648 |
| 3 | Amicis Research | Northridge | California | United States | 91324 |
| 4 | Excel Clinical Medical Trials | Boca Raton | Florida | United States | 33434 |
| 5 | Suncoast Clinical Research, Inc. - New Port Richey | New Port Richey | Florida | United States | 34652 |
| 6 | Suncoast Clinical Research, Inc. - Palm Harbor | New Port Richey | Florida | United States | 34652 |
| 7 | Progressive Medical Research | Port Orange | Florida | United States | 32127 |
| 8 | JSV Clinical Research Study, Inc | Tampa | Florida | United States | 33634 |
| 9 | Clinical Investigation Specialists, Inc | Gurnee | Illinois | United States | 60031 |
| 10 | Cardiovascular Research of Northwest Indiana, LLC | Munster | Indiana | United States | 46321 |
| 11 | West Broadway Clinic | Council Bluffs | Iowa | United States | 51501 |
| 12 | Louisville Metabolic and Atherosclerosis Research Center | Louisville | Kentucky | United States | 40213 |
| 13 | Aa Mrc, Llc | Flint | Michigan | United States | 48504 |
| 14 | Clinical Research of South Nevada | Las Vegas | Nevada | United States | 89104 |
| 15 | Green and Seidner Family Practice Associates | Lansdale | Pennsylvania | United States | 19446 |
| 16 | Health Concepts | Rapid City | South Dakota | United States | 57702 |
| 17 | Juno Research, LLC | Houston | Texas | United States | 77040 |
| 18 | FMC Science | Round Rock | Texas | United States | 78681 |
Sponsors and Collaborators
- Ionis Pharmaceuticals, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ISIS 678354-CS9
- 2022-501486-53