A Study of Olezarsen for the Treatment of Familial Chylomicronemia Syndrome (FCS) in Pediatric Participants

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.

Study Overview

• Status: Recruiting
• Conditions: Familial Chylomicronemia Syndrome
• Intervention / Treatment: Drug: Olezarsen

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ionis Pharmaceuticals, Inc.; Phone Number: (844) 200-6410; Email: IonisOlezarsenPediatric@clinicaltrialmedia.com

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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.
2. Must be able to comply with all study procedures.
3. 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).
4. Willing to fast for at least 10 hours before visits requiring fasted blood sampling.
5. 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.
6. 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.

Key Exclusion Criteria:

1. Diabetes mellitus with any of the following:

   1. Newly diagnosed within 12 weeks prior to screening or during the screening period.
   2. Hemoglobin A1c (HbA1c) ≥9.5% at screening.
   3. Change in basal insulin regimen >20% within 3 months prior to screening or during the screening period.
   4. For participants with type 1 diabetes: episode of diabetic ketoacidosis, or ≥3 episodes of severe hypoglycemia within 6 months prior to screening or during the screening period.
2. History of bleeding, diathesis, or coagulopathy.
3. Major surgery within 3 months of screening.
4. Plasma apheresis within 4 weeks prior to screening or planned during the study.
5. Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational agent, whichever is longer.
6. Active pancreatitis within 4 weeks prior to screening or during the screening period.
7. Malignancy diagnosed or treated within 5 years prior to screening or during the screening period.

Note: Other protocol-specified inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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.	Drug: Olezarsen; Olezarsen will be administered by subcutaneous injection.; Other Names: ISIS 678354
Experimental: Cohort 2; 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.	Drug: Olezarsen; Olezarsen will be administered by subcutaneous injection.; Other Names: ISIS 678354

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change from Baseline in Fasting Triglycerides (TG)	At 6 Months

Secondary Outcome Measures

Outcome Measure	Time Frame
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)	Up to 24 Months
Change From Baseline in Vital Sign Parameter - Heart Rate (Beats per Minute)	Baseline up to 24 Months
Change From Baseline in Vital Sign Parameter - Blood Pressure (Systolic and Diastolic, mmHg)	Baseline up to 24 Months
Change From Baseline in Vital Sign Parameter - Oxygen Saturation (%)	Baseline up to 24 Months
Change From Baseline in Vital Sign Parameter - Respiratory Rate (Breaths per Minute)	Baseline up to 24 Months
Change From Baseline in Vital Sign Parameter - Body Temperature (°C)	Baseline up to 24 Months
Change From Baseline in Body Weight (kg)	Baseline up to 24 Months
Change From Baseline in Height (cm)	Baseline up to 24 Months
Change From Baseline in Pubertal Development Parameter - Sexual Maturity Rating (Tanner Stage)	Baseline up to 24 Months
Change From Baseline in Pubertal Development Parameter - Menarche (Age to the Nearest Month and Year)	Baseline up to 24 Months
Change From Baseline in Clinical Laboratory Parameter - Amylase	Baseline up to 24 Months
Change From Baseline in Clinical Laboratory Parameter - Lipase	Baseline up to 24 Months
Change From Baseline in Clinical Laboratory Parameter - Alanine Aminotransferase (ALA)	Baseline up to 24 Months
Change From Baseline in Clinical Laboratory Parameter - Aspartate Aminotransferase (AST)	Baseline up to 24 Months
Change From Baseline in Clinical Laboratory Parameter - Platelets	Baseline up to 24 Months
Change From Baseline in Electrocardiogram (ECG) Parameter - Heart Rate	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)	Baseline up to 24 Months
Peak, Trough (Pre-Dose), and Post-treatment Plasma Concentration of Olezarsen	Up to 24 Months
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales	Baseline up to 24 Months
Change from Baseline in PedsQL Pediatric Pain Questionnaire (PPQ)	Baseline up to 24 Months
Change from Baseline in PedsQL Gastrointestinal Symptoms Module	Baseline up to 24 Months
Percent Change from Baseline in Fasting TG	Baseline, 3 Months, 12 Months, 18 Months, 24 Months
Proportion of Participants who Achieve Fasting TG <880 milligrams per deciliter (mg/dL)	3 Months, 6 Months, 12 Months, 18 Months, 24 Months
Proportion of Participants who Achieve Fasting TG <500 mg/dL	3 Months, 6 Months 12 Months, 18 Months, 24 Months
Proportion of Participants who Achieve ≥40 Percent (%) Reduction in Fasting TG from Baseline	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)	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)	Baseline, 3 Months, 6 Months, 12 Months, 18 Months, 24 Months
Event Rate of Adjudicated Acute Pancreatitis	3 Months, 12 Months, 18 Months, 24 Months
Percentage of Participants with Abdominal Pain Prior to First Dose vs. TEAEs	3 Months, 12 Months, 18 Months, 24 Months
Change From Baseline in Liver Size as Assessed by Magnetic Resonance Imaging (MRI)	Baseline, 12 Months, 24 Months
Change From Baseline in Liver Fat Content as Assessed by MRI	Baseline, 12 Months, 24 Months
Incidence of Anti-Drug Antibodies (ADA) to Olezarsen	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	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	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	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	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

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2031

Study Registration Dates

• First Submitted: July 10, 2026
• First Submitted That Met QC Criteria: July 22, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Familial hyperchylomicronemia syndrome; olezarsen
• Other Study ID Numbers: ISIS 678354-CS21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No