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

NCT05185843 | Active Not Recruiting Phase 3 FDA Drug

• 3 other identifiers: ISIS 678354-CS72021-003635-292023-508815-22-00
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 11

Brief Summary

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.

Conditions

Familial Chylomicronemia Syndrome

Keywords

FCS

Outcome Measures

Primary Outcomes (7)

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

  Baseline to Week 209

• Proportion of Participants With Clinical Bleeding Events

  Baseline to Week 209

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

  Baseline to Week 209

• Proportion of Participants With Urine Protein/Creatinine Ratio (UPCR) ≥1000 milligram (mg)/gram (g) or with Urine/Albumin Creatinine Ratio (UACR) ≥500 mg/g

  Baseline to Week 209

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

  Baseline to Week 209

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

  Baseline to Week 209

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

  Baseline to Week 209

Secondary Outcomes (14)

• Trough (Pre-Dose) Plasma Concentration of Olezarsen

  Up to 209 weeks

• Post-Treatment Plasma Concentration of Olezarsen

  Up to 209 weeks

• Change and Percent Change From Baseline in Fasting Triglycerides (TG)

  Baseline to Week 209

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

  Baseline to Week 209

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

  Baseline to Week 209

Study Arms (1)

Olezarsen

EXPERIMENTAL

Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 209 weeks.

Drug: Olezarsen

Interventions

Olezarsen DRUG

Olezarsen will be administered by SC injection.

Also known as: ISIS 678354, AKCEA-APOCIII-LRx

Olezarsen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (11)

Diabetes/Lipid Management & Research Center

Huntington Beach, California, 92648, United States

Location

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, 33434, United States

Location

University of Michigan, Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (MEND)

Ann Arbor, Michigan, 48109-2800, United States

Location

University of Rochester School of Medicine

Rochester, New York, 14642, United States

Location

Centre for Heart Lung Innovation

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

ARC Biosystems, Clinical Assessment Unit (CAU)

Vancouver, British Columbia, V6Z 2C7, Canada

Location

St. Boniface General Hospital

Winnipeg, Manitoba, R2H 2Ab, Canada

Location

Ecogene-21

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Clinique des Maladies Lipidiques de Quebec Inc.

Québec, Quebec, G1V 4W2, Canada

Location

Centre Hospitalier Universite de Sherbrooke (CHUS)

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Karolinska University Hospital Huddinge

Stockholm, 171 77, Sweden

Location

MeSH Terms

Conditions

Familial hyperchylomicronemia syndrome

Interventions

olezarsen

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 20, 2021
• First Posted: January 11, 2022
• Study Start: February 25, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (4); CA (6); SE (1)