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NCT Number: NCT05185843

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

The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of olezarsen (formerly known as AKCEA -APOCIII-LRX) in participants with FCS previously treated with volanesorsen.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Familial Chylomicronemia Syndrome Familial hyperchylomicronemia syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

ARC Biosystems, Clinical Assessment Unit (CAU), Vancouver, British Columbia, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria

  • 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

  • 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:

  • 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
  • Concomitant medication/procedure restrictions:
  • Systemic corticosteroids or anabolic steroids within 6 weeks prior to Screening and during the study unless approved by the Sponsor Medical Monitor
  • Plasma apheresis within 4 weeks prior to Screening or planned during the study

Treatment and study plan

Olezarsen

Drug

Olezarsen will be administered by SC injection.

Other names: ISIS 678354, AKCEA-APOCIII-LRx

Primary outcomes

  1. Proportion of Participants With Decrease in Platelet Count by >30% or >50%, or With Platelet Count Value <50,000/cubic millimeter (mm^3)

    Time frame: Baseline to Week 209

  2. Proportion of Participants With Clinical Bleeding Events

    Time frame: Baseline to Week 209

  3. Proportion of Participants With Decrease in Estimated Glomerular Filtration Rate (eGFR) by ≥30% or ≥50%

    Time frame: Baseline to Week 209

  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

    Time frame: Baseline to Week 209

  5. Proportion of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥5 x Upper Limit of Normal (ULN)

    Time frame: Baseline to Week 209

  6. Proportion of Participants With ALT or AST ≥3 x ULN and Total Bilirubin > 2 x ULN

    Time frame: Baseline to Week 209

  7. Proportion of Participants With Total Bilirubin ≥2 mg/deciliter (dL)

    Time frame: Baseline to Week 209

Secondary outcomes

  1. Trough (Pre-Dose) Plasma Concentration of Olezarsen

    Time frame: Up to 209 weeks

  2. Post-Treatment Plasma Concentration of Olezarsen

    Time frame: Up to 209 weeks

  3. Change and Percent Change From Baseline in Fasting Triglycerides (TG)

    Time frame: Baseline to Week 209

  4. Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III)

    Time frame: Baseline to Week 209

  5. Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C

    Time frame: Baseline to Week 209

  6. Change and Percent Change From Baseline in Fasting Chylomicron-TG

    Time frame: Baseline to Week 209

  7. Change and Percent Change From Baseline in Fasting Total Cholesterol (TC)

    Time frame: Baseline to Week 209

  8. Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C

    Time frame: Baseline to Week 209

  9. Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C

    Time frame: Baseline to Week 209

  10. Change and Percent Change From Baseline in Fasting Apoprotein B (apoB)

    Time frame: Baseline to Week 209

  11. Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48)

    Time frame: Baseline to Week 209

  12. Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C

    Time frame: Baseline to Week 209

  13. Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1)

    Time frame: Baseline to Week 209

  14. Event Rate of Acute Pancreatitis

    Time frame: Up to 209 weeks

Sponsors and collaborators

Lead sponsor

Ionis Pharmaceuticals, Inc.

Industry

Registry information

Official study title

An Open-Label Safety Study of AKCEA-APOCIII-LRX Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen (ISIS 304801)

Important dates

Study start
2022
Primary completion
2027
Study completion
2027
First posted
Jan 11, 2022
Registry last updated
Dec 12, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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