Severe Hypertriglyceridemia
Conditions
Keywords
Hypertriglyceridemia, Hyperlipidemias, Metabolic Diseases
Brief summary
The purpose of this study is to evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.
Detailed description
This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study in 446 participants. Participants will be randomized to receive olezarsen or placebo in a 53-week treatment period. The length of participation in the study will be approximately 78 weeks, which includes an up to 12-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period or transition to open-label extension (OLE) study with up to 1-year treatment.
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
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Fasting TG ≥ 500 mg/dL (5.65 mmol/L) at Screening and Qualification 2. Participants must be on lipid-lowering therapy that should adhere to standard of care (SOC) 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. 3. Participants must be willing to comply with diet and lifestyle recommendations as able.
Exclusion criteria
1. Hemoglobin A1c (HbA1c) ≥ 9.5% at Screening 2. Alanine aminotransferase or aspartate aminotransferase \> 3.0 × upper limit of normal 3. Total bilirubin \> 1.5 ULN unless due to Gilbert's syndrome 4. Estimated GFR \< 30 mL/min/1.73 m\^2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change from Baseline in Fasting TG Compared to Placebo | Baseline and Month 6 |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change from Baseline in Fasting Apolipoprotein C-III (ApoC-III), Remnant Cholesterol and Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Compared to Placebo | Baseline, Month 6 and 12 |
| Proportion of Patients Who Achieve Fasting TG <500 mg/dL (5.65 mmol/L) Compared to Placebo | Month 12 |
| Percent Change from Baseline in Fasting TG Compared to Placebo | Baseline and Month 12 |
| Adjudicated Acute Pancreatitis Event Rate During the Treatment Period Compared to Placebo | Week 1 through Week 53 |
| Absolute Change in Hepatic Fat Fraction (HFF) Between Olezarsen Treatment Group and Pooled Placebo | Baseline through Month 12 |
| Proportion of Participants Who Achieve Fasting TG < 880 mg/dL (10 mmol/L) Compared to Placebo in the Subgroup of Participants with Baseline TG ≥ 880 mg/dL | Month 12 |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Czechia, France, Greece, Hungary, India, Italy, Lithuania, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Slovakia, Spain, Sweden, Taiwan, United States
Outcome results
None listed