A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified November 2025 by Ionis Pharmaceuticals, Inc.
Sponsor
Ionis Pharmaceuticals, Inc.
Information Provided by (Responsible Party)
Ionis Pharmaceuticals, Inc.
Clinicaltrials.gov Identifier
NCT05185843
Other Study ID Numbers:
ISIS 678354-CS7
First Submitted
November 19, 2021
First Posted
January 10, 2022
Last Update Posted
December 11, 2025
Last Verified
November 2025

ClinicalTrials.gov processed this data on December 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

This is a Phase 3, multi-center, open-label safety study in 24 participants with FCS, previously treated with volanesorsen. The study consists of an 8- week screening period, treatment period up to week 209 and a 13-week follow-up period. Participants enrolled will receive olezarsen every 4 weeks during the 209-week Treatment Period.

Treatment period was extended to allow participants to receive olezarsen for an additional 52 weeks for a total of a 209-week treatment period until the drug may be commercially available in the patient's country, or until the Sponsor discontinues the olezarsen development program, whichever occurs earlier.

Condition or DiseaseIntervention/Treatment
Familial Chylomicronemia Syndrome
Drug: Olezarsen

Study Design

Study TypeInterventional
Actual Enrollment24 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleAn Open-Label Safety Study of AKCEA-APOCIII-LRX Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen (ISIS 304801)
Study Start DateFebruary 24, 2022
Actual Primary Completion Date1yr 1w from now
Actual Study Completion Date1yr 1w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Olezarsen
Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 209 weeks.
Drug: Olezarsen
Olezarsen will be administered by SC injection.

Outcome Measures

Primary Outcome Measures
  1. Proportion of Participants With Decrease in Platelet Count by >30% or >50%, or With Platelet Count Value <50,000/cubic millimeter (mm^3)
  2. Proportion of Participants With Clinical Bleeding Events
  3. Proportion of Participants With Decrease in Estimated Glomerular Filtration Rate (eGFR) by ≥30% or ≥50%
  4. Proportion of Participants With Urine Protein/Creatinine Ratio (UPCR) ≥1000 milligram (mg)/gram (g) or with Urine/Albumin Creatinine Ratio (UACR) ≥500 mg/g
  5. Proportion of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥5 x Upper Limit of Normal (ULN)
  6. Proportion of Participants With ALT or AST ≥3 x ULN and Total Bilirubin > 2 x ULN
  7. Proportion of Participants With Total Bilirubin ≥2 mg/deciliter (dL)
Secondary Outcome Measures
  1. Trough (Pre-Dose) Plasma Concentration of Olezarsen
  2. Post-Treatment Plasma Concentration of Olezarsen
  3. Change and Percent Change From Baseline in Fasting Triglycerides (TG)
  4. Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III)
  5. Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C
  6. Change and Percent Change From Baseline in Fasting Chylomicron-TG
  7. Change and Percent Change From Baseline in Fasting Total Cholesterol (TC)
  8. Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C
  9. Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C
  10. Change and Percent Change From Baseline in Fasting Apoprotein B (apoB)
  11. Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48)
  12. Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C
  13. Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1)
  14. Event Rate of Acute Pancreatitis

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Key Inclusion Criteria 1. Participants with FCS (clinical or genetic diagnosis) currently on or previously treated with volanesorsen (ISIS 304801) o Study participants in countries where Waylivra® is commercially approved and available for participants should not be deprived of the treatment option with Waylivra®. Participation in this study for such participants will only be allowed when Waylivra® was discontinued due to AEs 2. The following concomitant medications will be allowed if dosing regimen is expected to remain constant through the end of the study (occasional or intermittent use of over-the-counter (OTC) medications will be allowed at Investigator's discretion):
Statins, omega-3 fatty acids (prescription and OTC), fibrates, or other lipid-lowering medications. Participants taking OTC omega-3 fatty acids should make every effort to remain on the same brand through the end of the study
Antidiabetic medications
Oral anticoagulants (e.g., dabigatran, rivaroxaban, or apixaban, and warfarin with regular clinical monitoring)
Tamoxifen, estrogens or progestins Key
Exclusion Criteria
1. Treatment with another investigational drug (non-oligonucleotide), biological agent, or device within 4 weeks of Screening, or 5 half-lives of investigational agent, whichever is longer 2. Concomitant medication/procedure restrictions: 1. Systemic corticosteroids or anabolic steroids within 6 weeks prior to Screening and during the study unless approved by the Sponsor Medical Monitor 2. Plasma apheresis within 4 weeks prior to Screening or planned during the study

Contacts and Locations

Sponsors and CollaboratorsIonis Pharmaceuticals, Inc.
Locations
Diabetes/Lipid Management & Research Center | Huntington Beach California, United States, 92648Excel Medical Clinical Trials, LLC | Boca Raton Florida, United States, 33434University of Michigan, Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (MEND) | Ann Arbor Michigan, United States, 48109-2800University of Rochester School of Medicine | Rochester New York, United States, 14642Centre for Heart Lung Innovation | Vancouver British Columbia, Canada, V6Z 1Y6ARC Biosystems, Clinical Assessment Unit (CAU) | Vancouver British Columbia, Canada, V6Z 2C7St. Boniface General Hospital | Winnipeg Manitoba, Canada, R2H 2AbEcogene-21 | Chicoutimi Quebec, Canada, G7H 7K9Clinique des Maladies Lipidiques de Quebec Inc. | Québec Quebec, Canada, G1V 4W2Centre Hospitalier Universite de Sherbrooke (CHUS) | Sherbrooke Quebec, Canada, J1H 5N4Karolinska University Hospital Huddinge | Stockholm , Sweden, 171 77