A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia

Phase 3

Active, not recruiting

• Conditions: Severe Hypertriglyceridemia
• Interventions: Drug: Placebo; Drug: Olezarsen

• Registration Number: NCT05552326
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

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.

Study Timeline

• Study Start: 2022-08-31
• Study First Submitted: 2022-09-20
• Study First Submitted QC: 2022-09-20
• Study First Posted: 2022-09-23
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-29
• Primary Completion: 2025-06
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 446

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Olezarsen-matching placebo will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.
Olezarsen	Olezarsen	Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 49.

Primary Outcome Measures

Name	Time	Method
Percent Change from Baseline in Fasting TG Compared to Placebo	Baseline and Month 6

Secondary Outcome Measures

Name	Time	Method
Percent Change from Baseline in Fasting TG Compared to Placebo	Baseline and Month 12
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 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
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 Patients Who Achieve Fasting TG <500 mg/dL (5.65 mmol/L) Compared to Placebo	Month 12

Trial Locations

Locations (202)

Central Research Associates, Inc.; 🇺🇸 Birmingham, Alabama, United States

Alabama Clinical Therapeutics, LLC Alabaster; 🇺🇸 Birmingham, Alabama, United States

Onyx Clinical Research; 🇺🇸 Rochester Hills, Michigan, United States

NRC Research Institute; 🇺🇸 Los Angeles, California, United States

Accel Research Sites; 🇺🇸 DeLand, Florida, United States

Finlay Medical Research; 🇺🇸 Greenacres City, Florida, United States

University of Florida Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Meridien Research; 🇺🇸 Maitland, Florida, United States

Columbus Clinical Services; 🇺🇸 Miami, Florida, United States

Harmony Clinical Research, Inc; 🇺🇸 North Miami Beach, Florida, United States

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