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

Official title

An Open-Label Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Pediatric Patients With Familial Chylomicronemia Syndrome (FCS)

Overview

The primary purpose of the study is to evaluate the efficacy of olezarsen administered by subcutaneous injection to pediatric participants with FCS.

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.

Interventions

• Drug Olezarsen
  Olezarsen will be administered by subcutaneous injection.

Primary outcome measures

• Percent Change from Baseline in Fasting Triglycerides (TG) [Time frame: At 6 Months]

Secondary outcome measures (12)

• 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) [Time frame: Up to 24 Months]
• Change From Baseline in Vital Sign Parameter - Heart Rate (Beats per Minute) [Time frame: Baseline up to 24 Months]
• Change From Baseline in Vital Sign Parameter - Blood Pressure (Systolic and Diastolic, mmHg) [Time frame: Baseline up to 24 Months]
• Change From Baseline in Vital Sign Parameter - Oxygen Saturation (%) [Time frame: Baseline up to 24 Months]
• Change From Baseline in Vital Sign Parameter - Respiratory Rate (Breaths per Minute) [Time frame: Baseline up to 24 Months]
• Change From Baseline in Vital Sign Parameter - Body Temperature (°C) [Time frame: Baseline up to 24 Months]
• Change From Baseline in Body Weight (kg) [Time frame: Baseline up to 24 Months]
• Change From Baseline in Height (cm) [Time frame: Baseline up to 24 Months]
• Change From Baseline in Pubertal Development Parameter - Sexual Maturity Rating (Tanner Stage) [Time frame: Baseline up to 24 Months]
• Change From Baseline in Pubertal Development Parameter - Menarche (Age to the Nearest Month and Year) [Time frame: Baseline up to 24 Months]
• Change From Baseline in Clinical Laboratory Parameter - Amylase [Time frame: Baseline up to 24 Months]
• Change From Baseline in Clinical Laboratory Parameter - Lipase [Time frame: Baseline up to 24 Months]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• 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.
• History of bleeding, diathesis, or coagulopathy.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• UCSF Benioff Children's Hospital — San Francisco
• University of Texas Southwestern Medical Center — Dallas
• Cook Children's Medical Center — Fort Worth

Identifiers

NCT: NCT07727538 · ISIS 678354-CS21

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗