Familial Chylomicronemia SyndromePhase 3NCT05130450
A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Participants With Familial Chylomicronemia Syndrome (FCS)
A Phase 3 study testing Olezarsen in people with Familial Chylomicronemia Syndrome, run by Ionis Pharmaceuticals, Inc. at 27 sites in 11 countries.
Trial summary
The purpose of this study is to evaluate the effect of olezarsen (formerly known as AKCEA-APOCIII-LRx) on the percent change in fasting triglycerides (TG) from baseline. 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
- 60 participants
- Where
- 27 sitesin 11 countries
- Study dates
- 18 Nov 2021to Feb 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Satisfactory completion of treatment with olezarsen in the index study (ISIS 678354-CS3, last dose as scheduled at Week 49) with an acceptable safety profile, per Investigator judgement.
Who cannot join
- 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 patient participating in or completing the study, including need for treatment with medications disallowed in the index study (ISIS 678354-CS3).
Trial locations and contacts
27 sites in 11 countries.
27 sites in 11 countries
United States7 sites
Excel Medical Clinical Trials, LLC
Boca Raton, Florida, 33434
Diabetes/Lipid Management & Research Center
Huntington Beach, California, 92648
University of Kansas Medical Center (KUMC)
Kansas City, Kansas, 66160
CTSI Investigational Pharmacy
New York, New York, 10016
Milstein Hospital
New York, New York, 10032
Department of Pharmacy
Park Ridge, Illinois, 60068
IDS Central
Philadelphia, Pennsylvania, 19104
Canada4 sites
Ecogene-21
Chicoutimi, Quebec, G7H 7K9
Institute de Recherches Cliniques de Montreal
Montreal, Quebec, H2W 1R7
Nathalie Saint-Pierre
Montreal, Quebec, H2W 1R7
Clinique des Maladies Lipidiques de Quebec Inc.
Québec, Quebec, G1V 4W2
France3 sites
Groupement Hospitalier Est- Pharmacie Secteur Essais Clinique
Bron, 69677
Hôpital Bicêtre
Le Kremlin-Bicêtre, 94270
Pharmacie Hopital de la Conception
Marseille, 05 13385
Italy3 sites
Via Sergio Pansini 5
Naples, 80131
UOC di Farmacia AOUP PAOLO GIACCONE
Palermo, 90127
Azienda Ospedaliero Universitaria Policlinico Umberto I
Rome, 00161
Spain3 sites
Hospital Clínic Barcelona C/ Villarroel
Barcelona, 08036
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Virgen del Rocío
Seville, 41013
Portugal2 sites
Hospital da Senhora da Oliveira Guimaraes
Creixomil, 4835-044
Dra Margarida Falcao Centro Hospitalar Lisboa Ocidental Hospital Egas Moniz
Lisbon, 1340-019
Netherlands1 site
Academisch Medisch Centrum Goederenontvangst Apotheek t.a.v. Kenniscentrum
Amsterdam, Noor-Holland, 1105 AZ
United Kingdom1 site
Royal Manchester Children's Hospital
Manchester, M13 9WL
About this study
Official title: An Open-Label Extension Study of AKCEA-APOCIII-LRx Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
The purpose of this study is to evaluate the effect of olezarsen (formerly known as AKCEA-APOCIII-LRx) on the percent change in fasting triglycerides (TG) from baseline.
Read the detailed description
This is a multi-center, open-label extension (OLE) study of up to 60 participants with FCS rolling-over from Study ISIS 678354-CS3 (NCT04568434). Participants will receive olezarsen during a 157-week treatment period, followed by a 13-week post-treatment follow-up period. The length of participation in this study is approximately 201 weeks, which includes an up to 31-day qualification period, a 157-week treatment period, and a 13-week post-treatment evaluation period.
Treatment has been extended to obtain additional safety assessments and efficacy data and to provide patients with continued access to ISIS 678354 until the drug may be available commercially.
- 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 from Week 1 through Week 153. Receives: Drug: Olezarsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Fasting TG at 6 Months (Average of Weeks 23, 25, and 27) Compared to Baseline
Measured: Baseline and 6 months
Secondary outcomes (18)
Percent Change From Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) at 24 Months (Average of Week 103 and Week 105) and 36 Months (Average of Week 155 and Week 157)
Measured: Baseline and 36 months
Percentage of Participants Who Achieve ≥ 40% Reduction in Fasting TG From Baseline at 6 Months
Measured: At 6 months
Percentage of Participants Who Achieve ≥ 40% Reduction in Fasting TG From Baseline at 12, 24, 36 Months
Measured: At 12, 24, 36 months
Percent Change in Fasting apoC-III from Baseline at Month 6
Measured: Baseline and 6 months
Percent Change in Fasting apoC-III from Month 12, 24, 36
Measured: At 12, 24, 36 months
Percent Change From Baseline in Fasting Apolipoprotein 48 (apoB48) at 6 Months
Measured: At 6 months
Percent Change From Baseline in Fasting apoB48 at 12, 24, 36 Months
Measured: At 12, 24, 36 months
Percent Change in Fasting non-HDL-C from Baseline at Month 6
Measured: Baseline and 6 months
Percent Change in Fasting non-HDL-C from Months 12, 24, 36
Measured: At 12, 24, 36 months
Percentage of Participants Who Achieve Fasting TG ≤ 880 milligrams per deciliter (mg/dL) at 6 Months
Measured: At 6 months
Percentage of Participants Who Achieve Fasting TG ≤ 880 mg/dL at 12, 24, 36 months
Measured: At 12, 24, 36 months
Adjudicated Acute Pancreatitis Event Rate During the Treatment Period in Participants With ≥ 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Treatment With Study Drug in the Index Study
Measured: Week 1 through Week 157
Adjudicated Acute Pancreatitis Event Rate During the Treatment Period
Measured: Week 1 through Weeks 53, 105, or 157
Adjudicated Acute Pancreatitis Event Rate During the Treatment Period in Patients with a Prior History of Pancreatitis within 10 Years Prior to Screening in the Index Study
Measured: Week 1 through Weeks 53, 105, or 157
Percentage of Participants Who Achieve ≥ 70% Reduction in Fasting TG From Baseline at 6 Months
Measured: At 6 months
Percentage of Participants Who Achieve ≥ 70% Reduction in Fasting TG From Baseline at 12, 24, 36 Months
Measured: At 12, 24, 36 months
Percentage of Participants Who Achieve Fasting TG ≤ 500 mg/dL at 6 Months
Measured: At 6 months
Percentage of Participants Who Achieve Fasting TG ≤ 500 mg/dL at 12, 24, 36 Months
Measured: At 12, 24, 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2021
- Study start18 Nov 2021
- Primary completionFeb 2028 (estimated)
- Study completionFeb 2028 (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
- 60 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
- NCT05130450
- Sponsor's protocol ID
- ISIS 678354-CS13
- Other IDs
- 2021-003280-95
- Status last verified
- Dec 2025
- First submitted
- 11 Nov 2021
- Last updated
- 12 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- 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
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Extension Study of AKCEA-APOCIII-LRx Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS)
- ClinicalTrials.gov ID
- NCT05130450
- Acronym / sponsor ID
- ISIS 678354-CS13
- Conditions
- Familial Chylomicronemia Syndrome
- Keywords
- FCS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 18 Nov 2021 (actual)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- Feb 2028 (estimated)
- First posted
- 23 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the effect of olezarsen (formerly known as AKCEA-APOCIII-LRx) on the percent change in fasting triglycerides (TG) from baseline.
Detailed description
This is a multi-center, open-label extension (OLE) study of up to 60 participants with FCS rolling-over from Study ISIS 678354-CS3 (NCT04568434). Participants will receive olezarsen during a 157-week treatment period, followed by a 13-week post-treatment follow-up period. The length of participation in this study is approximately 201 weeks, which includes an up to 31-day qualification period, a 157-week treatment period, and a 13-week post-treatment evaluation period.
Treatment has been extended to obtain additional safety assessments and efficacy data and to provide patients with continued access to ISIS 678354 until the drug may be available commercially.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olezarsen | Experimental | Drug: OlezarsenOlezarsen will be administered once every 4 weeks by subcutaneous (SC) injection from Week 1 through Week 153. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Satisfactory completion of treatment with olezarsen in the index study (ISIS 678354-CS3, last dose as scheduled at Week 49) with an acceptable safety profile, per Investigator judgement.
Key exclusion criteria (1 listed)
- 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 patient participating in or completing the study, including need for treatment with medications disallowed in the index study (ISIS 678354-CS3).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlezarsenAlso: ISIS 678354, AKCEA -APOCIII-LRxOlezarsen will be administered by SC injection. | Drug | Olezarsen |
Primary outcome
Percent Change From Baseline in Fasting TG at 6 Months (Average of Weeks 23, 25, and 27) Compared to Baseline
Time frame: Baseline and 6 months
18 secondary outcomes
Percent Change From Baseline in Fasting TG at 12 Months (Average of Weeks 51 and 53) at 24 Months (Average of Week 103 and Week 105) and 36 Months (Average of Week 155 and Week 157)
Time frame: Baseline and 36 months
Percentage of Participants Who Achieve ≥ 40% Reduction in Fasting TG From Baseline at 6 Months
Time frame: At 6 months
Percentage of Participants Who Achieve ≥ 40% Reduction in Fasting TG From Baseline at 12, 24, 36 Months
Time frame: At 12, 24, 36 months
Percent Change in Fasting apoC-III from Baseline at Month 6
Time frame: Baseline and 6 months
Percent Change in Fasting apoC-III from Month 12, 24, 36
Time frame: At 12, 24, 36 months
Percent Change From Baseline in Fasting Apolipoprotein 48 (apoB48) at 6 Months
Time frame: At 6 months
Percent Change From Baseline in Fasting apoB48 at 12, 24, 36 Months
Time frame: At 12, 24, 36 months
Percent Change in Fasting non-HDL-C from Baseline at Month 6
Time frame: Baseline and 6 months
Percent Change in Fasting non-HDL-C from Months 12, 24, 36
Time frame: At 12, 24, 36 months
Percentage of Participants Who Achieve Fasting TG ≤ 880 milligrams per deciliter (mg/dL) at 6 Months
Time frame: At 6 months
Percentage of Participants Who Achieve Fasting TG ≤ 880 mg/dL at 12, 24, 36 months
Time frame: At 12, 24, 36 months
Adjudicated Acute Pancreatitis Event Rate During the Treatment Period in Participants With ≥ 2 Events of Adjudicated Acute Pancreatitis in 5 Years Prior to Treatment With Study Drug in the Index Study
Time frame: Week 1 through Week 157
Adjudicated Acute Pancreatitis Event Rate During the Treatment Period
Time frame: Week 1 through Weeks 53, 105, or 157
Adjudicated Acute Pancreatitis Event Rate During the Treatment Period in Patients with a Prior History of Pancreatitis within 10 Years Prior to Screening in the Index Study
Time frame: Week 1 through Weeks 53, 105, or 157
Percentage of Participants Who Achieve ≥ 70% Reduction in Fasting TG From Baseline at 6 Months
Time frame: At 6 months
Percentage of Participants Who Achieve ≥ 70% Reduction in Fasting TG From Baseline at 12, 24, 36 Months
Time frame: At 12, 24, 36 months
Percentage of Participants Who Achieve Fasting TG ≤ 500 mg/dL at 6 Months
Time frame: At 6 months
Percentage of Participants Who Achieve Fasting TG ≤ 500 mg/dL at 12, 24, 36 Months
Time frame: At 12, 24, 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2025.
- Individual participant dataSharing planned: 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/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
27 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Olezarsen in people with Familial Chylomicronemia Syndrome, run by Ionis Pharmaceuticals, Inc. at 27 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Canada, France, Italy, Spain and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in Fasting TG at 6 Months (Average of Weeks 23, 25, and 27) Compared to Baseline (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2025.