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Evaluating Olezarsen for Severe Hypertriglyceridemia

An Open-Label Extension Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Patients With Severe Hypertriglyceridemia (SHTG)

Phase 3 Interventional Ionis Pharmaceuticals, Inc. · NCT05681351

This study is testing whether the treatment olezarsen is safe and well-tolerated for people with severe high triglycerides who are already on other cholesterol-lowering medications.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment800 (estimated)
Ages18 Years and up
SexAll
SponsorIonis Pharmaceuticals, Inc. Industry-sponsored
Locations255 sites (Los Angeles, California and 254 other locations)
Trial IDNCT05681351 on ClinicalTrials.gov

What this trial studies

This study is an open-label extension involving approximately 800 participants with severe hypertriglyceridemia (SHTG) who are transitioning from previous studies. Participants will receive the treatment olezarsen over a 157-week period following a 31-day qualification phase. The study aims to assess the safety and tolerability of olezarsen while participants remain on a stable lipid-lowering therapy regimen. The study will also include a 13-week post-treatment observation period to monitor long-term effects.

Who should consider this trial

Good fit: Ideal candidates are individuals who have completed prior studies with olezarsen and have an acceptable safety profile.

Not a fit: Patients who have not completed the previous studies or those with unstable lipid-lowering therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve lipid levels and overall health outcomes for patients with severe hypertriglyceridemia.

How similar studies have performed: Previous studies involving olezarsen have shown promising results, indicating a potential for success in this extension study.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key 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.

Where this trial is running

Los Angeles, California and 254 other locations

+205 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Severe HypertriglyceridemiaISIS 678354Olezarsen
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.