Familial Chylomicronemia SyndromePhase 3NCT05185843
A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen
A Phase 3 study testing Olezarsen in people with Familial Chylomicronemia Syndrome, run by Ionis Pharmaceuticals, Inc. at 11 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Chylomicronemia Syndrome
- What is being tested?
- Olezarsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 11 sitesin 3 countries
- Study dates
- 25 Feb 2022to Jun 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
Canada6 sites
Ecogene-21
Chicoutimi, Quebec, G7H 7K9
Clinique des Maladies Lipidiques de Quebec Inc.
Québec, Quebec, G1V 4W2
Centre Hospitalier Universite de Sherbrooke (CHUS)
Sherbrooke, Quebec, J1H 5N4
Centre for Heart Lung Innovation
Vancouver, British Columbia, V6Z 1Y6
ARC Biosystems, Clinical Assessment Unit (CAU)
Vancouver, British Columbia, V6Z 2C7
St. Boniface General Hospital
Winnipeg, Manitoba, R2H 2Ab
United States4 sites
University of Michigan, Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (MEND)
Ann Arbor, Michigan, 48109-2800
Excel Medical Clinical Trials, LLC
Boca Raton, Florida, 33434
Diabetes/Lipid Management & Research Center
Huntington Beach, California, 92648
University of Rochester School of Medicine
Rochester, New York, 14642
About this study
Official 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)
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.
Read the detailed 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.
- Conditions
- Familial Chylomicronemia Syndrome
- Being tested
- Olezarsen
- Keywords
- FCS
- Medical subject headings
- Familial hyperchylomicronemia syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlezarsenDrug
Also called ISIS 678354, AKCEA-APOCIII-LRx
Olezarsen will be administered by SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Olezarsen | Experimental | Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 209 weeks. Receives: Drug: Olezarsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants With Decrease in Platelet Count by >30% or >50%, or With Platelet Count Value <50,000/cubic millimeter (mm^3)
Measured: Baseline to Week 209
Proportion of Participants With Clinical Bleeding Events
Measured: Baseline to Week 209
Proportion of Participants With Decrease in Estimated Glomerular Filtration Rate (eGFR) by ≥30% or ≥50%
Measured: 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
Measured: Baseline to Week 209
Proportion of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥5 x Upper Limit of Normal (ULN)
Measured: Baseline to Week 209
Proportion of Participants With ALT or AST ≥3 x ULN and Total Bilirubin > 2 x ULN
Measured: Baseline to Week 209
Proportion of Participants With Total Bilirubin ≥2 mg/deciliter (dL)
Measured: Baseline to Week 209
Secondary outcomes (14)
Trough (Pre-Dose) Plasma Concentration of Olezarsen
Measured: Up to 209 weeks
Post-Treatment Plasma Concentration of Olezarsen
Measured: Up to 209 weeks
Change and Percent Change From Baseline in Fasting Triglycerides (TG)
Measured: Baseline to Week 209
Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III)
Measured: Baseline to Week 209
Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C
Measured: Baseline to Week 209
Change and Percent Change From Baseline in Fasting Chylomicron-TG
Measured: Baseline to Week 209
Change and Percent Change From Baseline in Fasting Total Cholesterol (TC)
Measured: Baseline to Week 209
Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C
Measured: Baseline to Week 209
Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C
Measured: Baseline to Week 209
Change and Percent Change From Baseline in Fasting Apoprotein B (apoB)
Measured: Baseline to Week 209
Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48)
Measured: Baseline to Week 209
Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C
Measured: Baseline to Week 209
Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1)
Measured: Baseline to Week 209
Event Rate of Acute Pancreatitis
Measured: Up to 209 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2022
- Study start25 Feb 2022
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial Chylomicronemia SyndromeStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05185843
- Sponsor's protocol ID
- ISIS 678354-CS7
- Other IDs
- 2021-003635-29, 2023-508815-22-00, 2023
- Status last verified
- Dec 2025
- First submitted
- 20 Nov 2021
- Last updated
- 12 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
- Expanded access
- Available