Familial Chylomicronemia SyndromePhase 3NCT07727538
A Study of Olezarsen for the Treatment of Familial Chylomicronemia Syndrome (FCS) in Pediatric Participants
A Phase 3 study testing Olezarsen in people with Familial Chylomicronemia Syndrome, run by Ionis Pharmaceuticals, Inc. at 5 sites in United States.
Trial summary
The primary purpose of the study is to evaluate the efficacy of olezarsen administered by subcutaneous injection to pediatric participants with FCS. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- 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
- 12 participants
- Where
- 5 sitesUnited States
- Study dates
- 31 Jul 2026to Aug 2031
- 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 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Parental or legally authorized representative consent must be obtained, and the participants must provide age-appropriate or cognition-appropriate assent, as determined by the Investigator. The parent or legal guardian must be able to understand and comply with the study visit schedule and all other study procedures.
- Must be able to comply with all study procedures.
- Age 12 to less than 18 years at the time of informed consent/assent (Cohort 1); age 2 to less than 12 years at time of informed consent/assent (Cohort 2).
- Willing to fast for at least 10 hours before visits requiring fasted blood sampling.
- A diagnosis of Familial Chylomicronemia Syndrome (type 1 Hyperlipoproteinemia) by documentation of confirmed homozygote, compound heterozygote or double heterozygote for loss-of-function mutations in type 1-causing genes.
- Fasting TGs ≥880 mg/dL at screening. If fasting TG is < 880 mg/dL, up to two additional tests may be performed during the screening period with any single test used to qualify.
Who cannot join
- Diabetes mellitus with any of the following:
- Newly diagnosed within 12 weeks prior to screening or during the screening period.
- Hemoglobin A1c (HbA1c) ≥9.5% at screening.
- Change in basal insulin regimen >20% within 3 months prior to screening or during the screening period.
- Type 1 diabetes.
- History of bleeding, diathesis, or coagulopathy.
Show all 12Show fewer
- Major surgery within 3 months of screening.
- Plasma apheresis within 4 weeks prior to screening or planned during the study.
- Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational agent, whichever is longer.
- Active pancreatitis within 4 weeks prior to screening or during the screening period.
- Malignancy diagnosed or treated within 5 years prior to screening or during the screening period.
- Note: Other protocol-specified inclusion/exclusion criteria may apply.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University of Alabama
Birmingham, Alabama, 35294
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
- Recruiting
Cook Children's Medical Center
Fort Worth, Texas, 76104
- Recruiting
UCSF Benioff Children's Hospital
San Francisco, California, 94143
- Recruiting
Mary Bridge Children's
Tacoma, Washington, 98405
About this study
Official title: An Open-Label Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Pediatric Patients With Familial Chylomicronemia Syndrome (FCS)
The primary purpose of the study is to evaluate the efficacy of olezarsen administered by subcutaneous injection to pediatric participants with FCS.
Read the detailed description
This is a Phase 3 multi-center open-label study to evaluate safety, pharmacokinetics (PK), efficacy, and pharmacodynamics (PD) of olezarsen in pediatric participants (aged 2 to less than (<)18 years) with FCS. This study consists of three to four periods with the following approximate timeframes: 1-month screening period, 1-year treatment period, an optional 1-year long-term extension treatment period, and a 3-month post-treatment follow-up period.
- Conditions
- Familial Chylomicronemia Syndrome
- Being tested
- Olezarsen
- 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
Olezarsen will be administered by subcutaneous injection.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Participants aged 12 to <18 years will receive multiple doses of olezarsen, at a dose level that depends on body weight, once every month by subcutaneous injection for up to 1 year. All participants may continue to the optional 1-year long-term extension period with the last dose received being after 2 years of treatment. Receives: Drug: Olezarsen |
| Cohort 2 | Experimental | Participants aged 2 to <12 years will receive multiple doses of olezarsen, at a dose level based on information obtained from Cohort 1, once every month by subcutaneous injection for up to 1 year. All participants may continue to the optional 1-year long-term extension period with the last dose received being after 2 years of treatment. 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 Triglycerides (TG)
Measured: At 6 Months
Secondary outcomes (36)
Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Including Independently Adjudicated Events of Pancreatitis, and Withdrawals due to Adverse Events (AEs)
Measured: Up to 24 Months
Change From Baseline in Vital Sign Parameter - Heart Rate (Beats per Minute)
Measured: Baseline up to 24 Months
Change From Baseline in Vital Sign Parameter - Blood Pressure (Systolic and Diastolic, mmHg)
Measured: Baseline up to 24 Months
Change From Baseline in Vital Sign Parameter - Oxygen Saturation (%)
Measured: Baseline up to 24 Months
Change From Baseline in Vital Sign Parameter - Respiratory Rate (Breaths per Minute)
Measured: Baseline up to 24 Months
Change From Baseline in Vital Sign Parameter - Body Temperature (°C)
Measured: Baseline up to 24 Months
Change From Baseline in Body Weight (kg)
Measured: Baseline up to 24 Months
Change From Baseline in Height (cm)
Measured: Baseline up to 24 Months
Change From Baseline in Pubertal Development Parameter - Sexual Maturity Rating (Tanner Stage)
Measured: Baseline up to 24 Months
Change From Baseline in Pubertal Development Parameter - Menarche (Age to the Nearest Month and Year)
Measured: Baseline up to 24 Months
Change From Baseline in Clinical Laboratory Parameter - Amylase
Measured: Baseline up to 24 Months
Change From Baseline in Clinical Laboratory Parameter - Lipase
Measured: Baseline up to 24 Months
Change From Baseline in Clinical Laboratory Parameter - Alanine Aminotransferase (ALA)
Measured: Baseline up to 24 Months
Change From Baseline in Clinical Laboratory Parameter - Aspartate Aminotransferase (AST)
Measured: Baseline up to 24 Months
Change From Baseline in Clinical Laboratory Parameter - Platelets
Measured: Baseline up to 24 Months
Change From Baseline in Electrocardiogram (ECG) Parameter - Heart Rate
Measured: Baseline up to 24 Months
Change From Baseline in ECG Parameters Including PR Interval, QRS Duration, QT Interval, and QT Corrected Interval Fridericia's (QTcF)
Measured: Baseline up to 24 Months
Peak, Trough (Pre-Dose), and Post-treatment Plasma Concentration of Olezarsen
Measured: Up to 24 Months
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales
Measured: Baseline up to 24 Months
Change from Baseline in PedsQL Pediatric Pain Questionnaire (PPQ)
Measured: Baseline up to 24 Months
Change from Baseline in PedsQL Gastrointestinal Symptoms Module
Measured: Baseline up to 24 Months
Percent Change from Baseline in Fasting TG
Measured: Baseline, 3 Months, 12 Months, 18 Months, 24 Months
Proportion of Participants who Achieve Fasting TG <880 milligrams per deciliter (mg/dL)
Measured: 3 Months, 6 Months, 12 Months, 18 Months, 24 Months
Proportion of Participants who Achieve Fasting TG <500 mg/dL
Measured: 3 Months, 6 Months, 12 Months, 18 Months, 24 Months
Proportion of Participants who Achieve ≥40 Percent (%) Reduction in Fasting TG from Baseline
Measured: 3 Months, 6 Months, 12 Months, 18 Months, 24 Months
Percent Change from Baseline in Apolipoprotein C-III (apoC-III), Very Low-density Lipoprotein Cholesterol (VLDL-C), Non High-density Lipoprotein Cholesterol (non-HDL-C)
Measured: Baseline, 3 Months, 6 Months, 12 Months, 18 Months, 24 Months
Percent Change from Baseline in High-density Lipoprotein Cholesterol (HDL-C) Low-density Lipoprotein Cholesterol (LDL-C), Apolipoprotein B (apoB), Apolipoprotein B-48 (ApoB-48)
Measured: Baseline, 3 Months, 6 Months, 12 Months, 18 Months, 24 Months
Event Rate of Adjudicated Acute Pancreatitis
Measured: 3 Months, 6 Months, 12 Months, 18 Months, 24 Months
Percentage of Participants with Abdominal Pain Prior to First Dose vs. TEAEs
Measured: 3 Months, 6 Months, 12 Months, 18 Months, 24 Months
Change From Baseline in Liver Size as Assessed by Magnetic Resonance Imaging (MRI)
Measured: Baseline, 12 Months, 24 Months
Change From Baseline in Liver Fat Content as Assessed by MRI
Measured: Baseline, 12 Months, 24 Months
Incidence of Anti-Drug Antibodies (ADA) to Olezarsen
Measured: Pre-dose on Days 1, 1 Month, 3 Months, 6 Months, 9 Months, 12 Months, 18 Months and 24 Months; and post-dose on Days 1 and 6 Months
Titer of ADA to Olezarsen
Measured: Pre-dose on Days 1, 1 Month, 3 Months, 6 Months, 9 Months, 12 Months, 18 Months and 24 Months; and post-dose on Days 1 and 6 Months
Incidence of Participants with Negative, Treatment-Unaffected, or Treatment-Emergent ADA to Olezarsen
Measured: Pre-dose on Days 1, 1 Month, 3 Months, 6 Months, 9 Months, 12 Months, 18 Months and 24 Months; and post-dose on Days 1 and 6 Months
Onset of Treatment-Emergent ADA to Olezarsen
Measured: Pre-dose on Days 1, 1 Month, 3 Months, 6 Months, 9 Months, 12 Months, 18 Months and 24 Months; and post-dose on Days 1 and 6 Months
Time to Onset of Treatment-Emergent ADA to Olezarsen
Measured: Pre-dose on Days 1, 1 Month, 3 Months, 6 Months, 9 Months, 12 Months, 18 Months and 24 Months; and post-dose on Days 1 and 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2026
- Study start31 Jul 2026
- Primary completionAug 2030 (estimated)
- Study completionAug 2031 (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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07727538
- Sponsor's protocol ID
- ISIS 678354-CS21
- Status last verified
- Oct 2026
- First submitted
- 10 Jul 2026
- Last updated
- 8 Oct 2026
- 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/.