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

Phase 3RecruitingNCT07727538

Ionis Pharmaceuticals, Inc.12 enrolled

Overview

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

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Familial Chylomicronemia Syndrome

Interventions

OlezarsenDRUG

Olezarsen will be administered by subcutaneous injection.

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 Years

Medical Language ↔ Plain English

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. Type 1 diabetes. 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.

Locations (4)

University of Alabama

Birmingham, Alabama, United States

RECRUITING

UCSF Benioff Children's Hospital

San Francisco, California, United States

RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, United States

RECRUITING

Outcomes

Primary Outcomes

Percent Change from Baseline in Fasting Triglycerides (TG)

Time frame: At 6 Months

Secondary Outcomes

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

Central Contacts

Ionis Pharmaceuticals, Inc.

CONTACT

(844) 200-6410 IonisOlezarsenPediatric@clinicaltrialmedia.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Cook Children's Medical Center

Fort Worth, Texas, United States

RECRUITING

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

Change From Baseline in Clinical Laboratory Parameter - Alanine Aminotransferase (ALA)

Time frame: Baseline up to 24 Months

Change From Baseline in Clinical Laboratory Parameter - Aspartate Aminotransferase (AST)

Time frame: Baseline up to 24 Months

Change From Baseline in Clinical Laboratory Parameter - Platelets

Time frame: Baseline up to 24 Months

Change From Baseline in Electrocardiogram (ECG) Parameter - Heart Rate

Time frame: 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)

Time frame: Baseline up to 24 Months

Peak, Trough (Pre-Dose), and Post-treatment Plasma Concentration of Olezarsen

Time frame: Up to 24 Months

Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales

Time frame: Baseline up to 24 Months

Change from Baseline in PedsQL Pediatric Pain Questionnaire (PPQ)

Time frame: Baseline up to 24 Months

Change from Baseline in PedsQL Gastrointestinal Symptoms Module

Time frame: Baseline up to 24 Months

Percent Change from Baseline in Fasting TG

Time frame: Baseline, 3 Months, 12 Months, 18 Months, 24 Months

Proportion of Participants who Achieve Fasting TG <880 milligrams per deciliter (mg/dL)

Time frame: 3 Months, 6 Months, 12 Months, 18 Months, 24 Months

Proportion of Participants who Achieve Fasting TG <500 mg/dL

Time frame: 3 Months, 6 Months, 12 Months, 18 Months, 24 Months

Proportion of Participants who Achieve ≥40 Percent (%) Reduction in Fasting TG from Baseline

Time frame: 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)

Time frame: 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)

Time frame: Baseline, 3 Months, 6 Months, 12 Months, 18 Months, 24 Months

Event Rate of Adjudicated Acute Pancreatitis

Time frame: 3 Months, 6 Months, 12 Months, 18 Months, 24 Months

Percentage of Participants with Abdominal Pain Prior to First Dose vs. TEAEs

Time frame: 3 Months, 6 Months, 12 Months, 18 Months, 24 Months

Change From Baseline in Liver Size as Assessed by Magnetic Resonance Imaging (MRI)

Time frame: Baseline, 12 Months, 24 Months

Change From Baseline in Liver Fat Content as Assessed by MRI

Time frame: Baseline, 12 Months, 24 Months

Incidence of Anti-Drug Antibodies (ADA) to Olezarsen

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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