CORE-OLE: A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG)

Phase 3

Recruiting

• Conditions: Severe Hypertriglyceridemia
• Interventions: Drug: Olezarsen

• Registration Number: NCT05681351
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of olezarsen in participants with SHTG.

Detailed Description

This is a multi-center, open-label extension (OLE) study of approximately 800 participants with SHTG who would be rolled over from studies ISIS 678354-CS5 (NCT05079919) or ISIS 678354-CS6 (NCT05552326). Day 1 of this study may be same as the Week 53 visit of either ISIS 678354-CS5 or ISIS 678354-CS6, as applicable. Participants will receive olezarsen during the 157-week treatment period. The study will include a 31-day qualification Period, a 157-week treatment period, and a 13-week post-treatment period.

Study Timeline

• Study Start: 2022-12-13
• Study First Submitted: 2022-12-25
• Study First Submitted QC: 2022-12-25
• Study First Posted: 2023-01-12
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-30
• Last Update Posted: 2025-08-01
• Primary Completion: 2027-03
• Study Completion: 2027-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 800

Inclusion Criteria

• Satisfactory completion of either ISIS 678354-CS5 or ISIS 678354-CS6 with an acceptable safety profile, per Investigator judgment. Satisfactory completion requires that the patient did not terminate early from treatment.
• Participants must be on a stable regimen of lipid-lowering therapy that should adhere to standard of care (SOC) per local guidelines. A patient may be eligible if their regimen of lipid-lowering therapy has been changed recently, provided that lipid lowering medications are optimized and stabilized for at least 4 weeks prior to the end of the Qualification Period of this OLE study; ideally, such changes are initiated after Week 53 of the index study (ISIS 678354-CS5 or CS6).
• A patient may re-enroll in the study after having completed the study when the Treatment Period was 53 weeks, if the patient satisfactorily completed the study with an acceptable safety profile, per Investigator judgment. In the case of re-enrollment, there is no limit on the time gap between completion of treatment under the previous protocol and dosing upon re-enrollment (i.e., may exceed 17 weeks between doses).

Key

Exclusion Criteria

• Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study, including need for treatment with disallowed medications, or need to change the required stable regimen as per either ISIS 678354-CS5 or ISIS 678354-CS6 study entry criteria. It is acceptable to adjust a regimen of lipid-lowering therapy as described in the second Key Inclusion Criterion above, and it is acceptable to adjust or stop lipid-lowering therapy at or after Week 13 per Investigator judgment.

NOTE: Other Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Olezarsen	Olezarsen	Participants who completed either ISIS 678354-CS5 (NCT05079919) or ISIS 678354-CS6 (NCT05552326) study would be enrolled to receive olezarsen, subcutaneous (SC) injection, once every 4 weeks from Week 1 through Week 153.

Primary Outcome Measures

Name	Time	Method
Proportion of Participants With Change in Clinical Laboratory Values From Baseline to Week 53, From Baseline to Week 105, and From Baseline to Week 157	Baseline up to Week 157
Proportion of Participants Who Experience Adverse Events (AEs)	Baseline up to Week 157
Proportion of Participants Who Use Concomitant Medications	Baseline up to Week 157

Trial Locations

Locations (261)

LA Universal Research Center, Inc.; 🇺🇸 Los Angeles, California, United States

University of California, San Diego (UCSD); 🇺🇸 San Diego, California, United States

Metabolic Institute of America; 🇺🇸 Tarzana, California, United States

Excel Medical Clinical Trials; 🇺🇸 Boca Raton, Florida, United States

Finlay Medical Research; 🇺🇸 Miami, Florida, United States

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

Innovia Research Center, Inc.; 🇺🇸 Miramar, Florida, United States

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

R & B Medical Center LLC; 🇺🇸 Tampa, Florida, United States

VICIS Clinical Research; 🇺🇸 Tampa, Florida, United States

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