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

Familial Chylomicronemia Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05185843
• Other study ID #: ISIS 678354-CS7
• Secondary ID: 2021-003635-29
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 25, 2022
• Est. completion date: June 2025

Study information

• Verified date: August 2023
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: June 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Familial Chylomicronemia Syndrome
• Hyperlipoproteinemia Type I
• Syndrome

Intervention

Drug:
• Olezarsen
Olezarsen will be administered by SC injection.

Locations

Country	Name	City	State
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	Clinique des Maladies Lipidiques de Quebec Inc.	Québec	Quebec
Canada	Centre Hospitalier Universite de Sherbrooke (CHUS)	Sherbrooke	Quebec
Canada	ARC Biosystems, Clinical Assessment Unit (CAU)	Vancouver	British Columbia
Canada	Centre for Heart Lung Innovation	Vancouver	British Columbia
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
Sweden	Karolinska University Hospital Huddinge	Stockholm
United States	University of Michigan, Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes (MEND)	Ann Arbor	Michigan
United States	Excel Medical Clinical Trials, LLC	Boca Raton	Florida
United States	Diabetes/Lipid Management & Research Center	Huntington Beach	California
United States	University of Rochester School of Medicine	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Proportion of Participants With Major or Clinically Relevant Non-major Bleeding Events		Baseline to Week 157
Primary	Proportion of Participants With Decrease in Estimated Glomerular Filtration Rate (eGFR) by >30% or >50%		Baseline to Week 157
Primary	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
Primary	Proportion of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) >5 x Upper Limit of Normal (ULN)		Baseline to Week 157
Primary	Proportion of Participants With ALT or AST >3 x ULN and Total Bilirubin > 2 x ULN		Baseline to Week 157
Primary	Proportion of Participants With Total Bilirubin >2 mg/deciliter (dL)		Baseline to Week 157
Secondary	Trough (Pre-Dose) Plasma Concentration of Olezarsen		Up to 157 weeks
Secondary	Post-Treatment Plasma Concentration of Olezarsen		Up to 170 weeks
Secondary	Change and Percent Change From Baseline in Fasting Triglycerides (TG)		Baseline to Week 157
Secondary	Change and Percent Change From Baseline in Fasting Apolipoprotein C-III (APOC-III)		Baseline to Week 157
Secondary	Change and Percent Change From Baseline in Fasting Very Low-Density Lipoprotein (VLDL)-C		Baseline to Week 157
Secondary	Change and Percent Change From Baseline in Fasting Chylomicron-TG		Baseline to Week 157
Secondary	Change and Percent Change From Baseline in Fasting Total Cholesterol (TC)		Baseline to Week 157
Secondary	Change and Percent Change From Baseline in Fasting Non-High-Density Lipoprotein (non-HDL)-C		Baseline to Week 157
Secondary	Change and Percent Change From Baseline in Fasting Low-Density Lipoprotein (LDL)-C		Baseline to Week 157
Secondary	Change and Percent Change From Baseline in Fasting Apoprotein B (apoB)		Baseline to Week 157
Secondary	Change and Percent Change From Baseline in Fasting Apoprotein B48 (apoB48)		Baseline to Week 157
Secondary	Change and Percent Change From Baseline in Fasting High-Density Lipoprotein (HDL)-C		Baseline to Week 157
Secondary	Change and Percent Change From Baseline in Fasting Apoprotein A-1 (ApoA-1)		Baseline to Week 157
Secondary	Event Rate of Acute Pancreatitis		Up to 157 weeks