A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen

An Open-Label Safety Study of AKCEA-APOCIII-LRX Administered Subcutaneously to Patients With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen (ISIS 304801)

The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of olezarsen (formerly known as AKCEA -APOCIII-LRX) in participants with FCS previously treated with volanesorsen.

Study Overview

• Status: Active, not recruiting
• Conditions: Familial Chylomicronemia Syndrome
• Intervention / Treatment: Drug: Olezarsen

Detailed Description

This is a Phase 3, multi-center, open-label safety study of up to 30 participants with FCS, previously treated with volanesorsen. The study consists of 3 periods: 1) Screening Period: Week -8 to Week -1 (up to 8 weeks); 2) Treatment Period up to Week 157; and 3) Post-Treatment Follow-up Period: Week 158 to Week 170 (12 weeks). Participants enrolled will receive olezarsen every 4 weeks during the 157-week Treatment Period.

This study was extended to allow participants to receive olezarsen for an additional 104 weeks following the initial 53-week treatment period.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ionis Pharmaceuticals; Phone Number: (844) 583-0450; Email: ionisNCT05130450study@clinicaltrialmedia.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Centre for Heart Lung Innovation
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • ARC Biosystems, Clinical Assessment Unit (CAU)
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2Ab
      • St. Boniface General Hospital
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Ecogene-21
    • Québec, Quebec, Canada, G1V 4W2
      • Clinique des Maladies Lipidiques de Quebec Inc.
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universite de Sherbrooke (CHUS)
• Sweden
  • Stockholm, Sweden, 171 77
    • Karolinska University Hospital Huddinge
• United States
  • California
    • Huntington Beach, California, United States, 92648
      • Diabetes/Lipid Management & Research Center
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials, LLC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-2800
      • University of Michigan, Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (MEND)
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Participants with FCS (clinical or genetic diagnosis) currently on or previously treated with volanesorsen (ISIS 304801)

   o Study participants in countries where Waylivra® is commercially approved and available for participants should not be deprived of the treatment option with Waylivra®. Participation in this study for such participants will only be allowed when Waylivra® was discontinued due to AEs

2. The following concomitant medications will be allowed if dosing regimen is expected to remain constant through the end of the study (occasional or intermittent use of over-the-counter (OTC) medications will be allowed at Investigator's discretion):

   • Statins, omega-3 fatty acids (prescription and OTC), fibrates, or other lipid-lowering medications. Participants taking OTC omega-3 fatty acids should make every effort to remain on the same brand through the end of the study
   • Antidiabetic medications
   • Oral anticoagulants (e.g., dabigatran, rivaroxaban, or apixaban, and warfarin with regular clinical monitoring)
   • Tamoxifen, estrogens or progestins

Exclusion Criteria:

1. Treatment with another investigational drug (non-oligonucleotide), biological agent, or device within 4 weeks of Screening, or 5 half-lives of investigational agent, whichever is longer

2. Concomitant medication/procedure restrictions:

   1. Systemic corticosteroids or anabolic steroids within 6 weeks prior to Screening and during the study unless approved by the Sponsor Medical Monitor
   2. Plasma apheresis within 4 weeks prior to Screening or planned during the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olezarsen; Olezarsen will be administered once every 4 weeks by subcutaneous (SC) injection for up to 153 weeks.	Drug: Olezarsen; Olezarsen will be administered by SC injection.; Other Names: ISIS 678354; AKCEA-APOCIII-LRx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Participants With Decrease in Platelet Count by >30% or >50%, or With Platelet Count Value <50,000/cubic millimeter (mm^3)	Baseline to Week 157
Proportion of Participants With Major or Clinically Relevant Non-major Bleeding Events	Baseline to Week 157
Proportion of Participants With Decrease in Estimated Glomerular Filtration Rate (eGFR) by >30% or >50%	Baseline to Week 157
Proportion of Participants With Urine Protein/Creatinine Ratio (UPCR) ≥1000 milligram (mg)/gram (g) or with Urine/Albumin Creatinine Ratio (UACR) ≥500 mg/g	Baseline to Week 157
Proportion of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >5 x Upper Limit of Normal (ULN)	Baseline to Week 157
Proportion of Participants With ALT or AST >3 x ULN and Total Bilirubin > 2 x ULN	Baseline to Week 157
Proportion of Participants With Total Bilirubin >2 mg/deciliter (dL)	Baseline to Week 157

Secondary Outcome Measures

Outcome Measure	Time Frame
Trough (Pre-Dose) Plasma Concentration of Olezarsen	Up to 157 weeks
Post-Treatment Plasma Concentration of Olezarsen	Up to 170 weeks
Change and Percent Change From Baseline in Fasting Triglycerides (TG)	Baseline to Week 157
Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III)	Baseline to Week 157
Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C	Baseline to Week 157
Change and Percent Change From Baseline in Fasting Chylomicron-TG	Baseline to Week 157
Change and Percent Change From Baseline in Fasting Total Cholesterol (TC)	Baseline to Week 157
Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C	Baseline to Week 157
Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C	Baseline to Week 157
Change and Percent Change From Baseline in Fasting Apoprotein B (apoB)	Baseline to Week 157
Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48)	Baseline to Week 157
Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C	Baseline to Week 157
Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1)	Baseline to Week 157
Event Rate of Acute Pancreatitis	Up to 157 weeks

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2022
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: November 20, 2021
• First Submitted That Met QC Criteria: December 22, 2021
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: FCS
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Syndrome; Hyperlipoproteinemia Type I
• Other Study ID Numbers: ISIS 678354-CS7; 2021-003635-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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